AU2013203770B2 - Eukaryotic organisms and methods for producing 1,3-butanediol - Google Patents

Abstract

Provided herein are non-naturally occurring eukaryotic organisms that can be engineered to produce and increase the availability of cytosolic acetyl-CoA. Also provided herein are non-naturally occurring eukaryotic organisms having a 1,3 butanediol (1,3-BDO) pathway, and methods of using such organisms to produce 1,3 4 a 0$ 40, 6 4 m > kk 04~ (A o'" Wn

Description

EUKARYOTIC ORGANISMS AND METHODS FOR PRODUCE ING 1,3-BUTANED11L The entire disclosure in the complete specification of our Australian Patent Application No. 2012304428 is by this cross-reference incorporated into the present specification. 1. BACKGROUND [00011 Provided herein are methods generally relating to biosynthetic processes and eukaryotic organisms capable of producing organic compounds. More specifically, in certain embodiments, provided herein are non-naturally occurring eukaryotic organisms that can be engineered to produce and increase the availability of cytosolic acetyl-CoA. In many eukaryotic organisms, acetyl-CoA is mainly synthesized by pyruvate dehydrogenase in the mitochondrion (FIG. 1). Thus, there exists a need to develop eukaryotic organisms that can produce and increase the availability of cytosolic acetyl-CoA. A mechanism for exporting acetyl-CoA from the mitochondrion to the cytosol enables deployment of a cytosolic production pathway that originates from acetyl-CoA. Such cytosolic production pathways include, for example, the production of commodity chemicals, such as 1,3-butanediol (1,3-BDO) and/or other compounds of interest. [00021 Also provided herein are non-naturally occurring eukaryotic organisms that can be engineered to produce 1,3-BDO. The reliance on petroleum based feedstocks for production of 1,3-131)0 warrants the development of alternative routes to producing 1,3-1DO and butadiene using renewable feedstocks. Thus, there exists a need to develop eukaryotic organisms and methods of their use to produce 1,3-131)0. [00031 The organisms and methods provided herein satisfy these needs and provides related advantages as well. -1- 2. SUMMARY [0004] Provided herein are non-naturally occurring eukaryotic organisms that can be engineered to produce and increase the availability of cytosolic acetyl-CoA. Such organisms would advantageously allow for the production of cytosolic acetyl-CoA, which can then be used by the organism to produce compounds of interest, such as 1,3-BDO, using a cytosolic production pathway. Also provided herein are non-naturally occurring eukaryotic organisms having a 1,3-BDO pathway. and methods of using such organisms to produce 1,3-BDO. [0004a] Particularly provided herein is a non-naturally occurring microbial organism comprising a 1,3-BDO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO, and: (1) wherein the organism: i. has lower or no enzymatic activity that converts acetoacetyl-CoA to acetoacetate as compared to a wild-type version of the organism; ii. comprises a disruption in an endogenous nucleic acid encoding an enzyme that converts acetoacetyl-CoA to acetoacetate; iii. expresses an attenuated acetoacetyl-CoA hydrolase or transferase; or iv. comprises a disruption in an endogenous nucleic acid encoding an acetoacetyl-CoA hydrolase or transferase. [0004b] In a further embodiment there is provided the organism described above: (1) wherein the organism: i. has lower or no enzymatic activity that converts 3-hydroxybutyryl CoA to 3-hydroxybutyrate as compared to a wild-type version of the organism; ii. comprises a disruption in an endogenous nucleic acid encoding an enzyme that converts 3-hydroxybutyryl-CoA to 3-hydroxybutyrate; 2 (followed by 2A) iii. expresses an attenuated 3-hydroxybutyryl-CoA hydrolase or transferase; or iv. comprises a disruption in an endogenous nucleic acid encoding a 3 hydroxybutyryl-CoA hydrolase or transferase; (2) wherein the organism: i. has lower or no enzymatic activity that converts 3 hydroxybutyraldehyde to 3-hydroxybutyrate as compared to a wild type version of the organism; ii. comprises a disruption in an endogenous nucleic acid encoding an enzyme that converts 3-hydroxybutyraldehyde to 3-hydroxybutyrate; iii. expresses an attenuated 3-hydroxybutyraldehyde dehydrogenase; or iv. comprises a disruption in an endogenous nucleic acid encoding a 3 hydroxybutyraldehyde dehydrogenase; (3) wherein the organism: i. has lower or no enzymatic activity that catalyzes 1,3-butanediol to 3 oxobutanol as compared to a wild-type version of the organism; ii. comprises a disruption in an endogenous nucleic acid encoding an enzyme that catalyzes 1,3-butanediol to 3-oxobutanol; iii. expresses an attenuated 1,3-butanediol dehydrogenase; or iv. comprises a disruption in an endogenous nucleic acid encoding a 1,3 butanediol dehydrogenase; (4) wherein the organism: i. has lower or no enzymatic activity that converts G3P to glycerol as compared to a wild-type version of the organism; 2A (followed by 2B) ii. comprises a disruption in an endogenous nucleic acid encoding an enzyme that converts G3P to glycerol; iii. expresses an attenuated G3P dehydrogenase or G3P phosphatase; or iv. comprises a disruption in an endogenous nucleic acid encoding a G3P dehydrogenase or a G3P phosphatase; (5) wherein the organism: i. has lower or no enzymatic activity that converts pyruvate to acetaldehyde as compared to a wild-type version of the organism; ii. comprises a disruption in an endogenous nucleic acid encoding an enzyme that converts pyruvate to acetaldehyde; iii. expresses an attenuated pyruvate decarboxylase; or iv. comprises a disruption in an endogenous nucleic acid encoding a pyruvate decarboxylase; or (6) wherein the organism: i. has lower or no enzymatic activity that converts acetyl-CoA to ethanol as compared to a wild-type version of the organism; ii. comprises a disruption in an endogenous nucleic acid encoding an enzyme that converts acetyl-CoA to ethanol; iii. expresses an attenuated ethanol dehydrogenase or acetaldehyde dehydrogenase;or iv. comprises a disruption in an endogenous nucleic acid encoding an ethanol dehydrogenase or acetaldehyde dehydrogenase. [0004c] Also provided is a method for producing 1,3-BDO, comprising culturing an organism described above under conditions and for a sufficient period of time to produce 1,3-BDO. 2B (followed by 2C) [0004d]Other aspects are described herein for completeness and may form the subject of the parent application, AU 2012304428. [0005] In a first aspect, provided herein is a non-naturally occurring eukaryotic organism comprising an acetyl-CoA pathway, wherein said organism comprises at least one exogenous nucleic acid encoding an acetyl-CoA pathway enzyme expressed in a sufficient amount to (i) transport acetyl-CoA from a mitochondrion and/or peroxisome of said organism to the cytosol of said organism, (ii) produce acetyl-CoA in the cytoplasm of said organism, and/or (iii) increase acetyl-CoA in the cytosol of said organism. In certain embodiments, the acetyl-CoA pathway comprises one or more enzymes selected from the group consisting of a citrate synthase; a citrate transporter; a citrate/oxaloacetate transporter; a citrate/malate transporter; an ATP citrate lyase; a citrate lyase; an acetyl-CoA synthetase; an oxaloacetate transporter; a cytosolic malate dehydrogenase; a malate transporter; a mitochondrial malate dehydrogenase; a pyruvate oxidase (acetate forming); an acetyl-CoA ligase or transferase; an acetate kinase; a phosphotransacetylase; a pyruvate decarboxylase; an acetaldehyde dehydrogenase; a pyruvate oxidase (acetyl-phosphate forming); a pyruvate dehydrogenase, a pyruvate:ferredoxin oxidoreductase or pyruvate formate lyase; a acetaldehyde dehydrogenase (acylating); a threonine aldolase; a mitochondrial acetylcarnitine transferase; a peroxisomal acetylcarnitine transferase; a cytosolic acetylcarnitine transferase; a mitochondrial acetylcarnitine translocase; a peroxisomal acetylcarnitine translocase; a phosphoenolpyruvate (PEP) carboxylase; a PEP carboxykinase; an oxaloacetate decarboxylase; a malonate semialdehyde dehydrogenase (acetylating); an acetyl-CoA carboxylase; a malonyl-CoA decarboxylase; an oxaloacetate dehydrogenase; an oxaloacetate oxidoreductase; a malonyl CoA reductase; a pyruvate carboxylase; a malonate semialdehyde dehydrogenase; a malonyl CoA synthetase; a malonyl-CoA transferase; a malic enzyme; a malate dehydrogenase; a malate oxidoreductase; a pyruvate kinase; and a PEP phosphatase. 2C (followed by 3) [00061 In another aspect, provided herein is a method for transporting acetyl-CoA from a mitochondrion and/or peroxisome to a cytosol of a non-naturally occurring eukaryotic organism, comprising culturing a non-naturally occurring eukaryotic organism comprising an acetyl-CoA pathway tinder conditions and for a sufficient period of time to transport the acetyl-CoA from a mitochondrion and/or peroxisome to a cytosol of the non-naturally occurring eukaryotic organism. In some embodiments, provided herein is a method for transporting acetyl-CoA from a mitochondrion to a cytosol of said non-naturally occurring eukaryotic organism. In other embodiments, provided herein is a method for transporting acetyl-CoA from a peroxisome to a cytosol of said non-naturally occurring eukaryotic organism. In some embodiments culturing a non-naturally occurring eukarvotic organism comprising an acetyl-CoA pathway, wherein said organism comprises at least one exogenous nucleic acid encoding an acetyl-CoA pathway enzyme expressed in a sufficient amount to transport acetyl-CoA from a mitochondrion and/or peroxisome of said organisnmi to the cytosol of said organism. In certain embodiments, the acetyl-CoA pathway comprises one or more enzymes selected from the group consisting of a citrate synthase; a citrate transporter; a citrate/oxaloacetate transporter; a citrate/malate transporter; an ATP citrate lyase; a citrate lyase; an acetyl-CoA synthetase; an oxaloacetate transporter; a cytosolic malate dehydrogenase; a malate transporter; a mitochondrial malate dehydrogenase; a pyruvate oxidase (acetate forming); an acetyl-CoA ligase or transferase; an acetate kinase; a phosphotransacetylase; a pyruvate decarboxylase; an acetaldehyde dehydrogenase; a pyruvate oxidase (acetyl-phosphate forming); a pyruvate dehydrogenase, a pyruvate:ferredoxin oxidoreductase or pyruvate formate lyase; a acetaldehyde dehydrogenase (acylating); a threonine aldolase; a mitochondrial acetyicarnitine transferase; a peroxisomal acetylcarnitine transferase; a cytosolic acetylcarnitine transferase; a mitochondrial acetylearnitine translocase; and a peroxisomal acetylcamitine translocase; a PEP carboxylase; a PEP carboxykinase; an oxaloacetate decarboxylase; a malonate semialdehyde dehydrogenase (acetylating); an acetyl-CoA carboxylase; a malonyl-CoA decarboxylase; an oxaloacetate dehydrogenase; an oxaloacetate oxidoreductase; a malonyl -CoA reductase; a pyruvate carboxylase; a malonate semialdehyde dehydrogenase; a malonyl-CoA synthetase; a malonyl CoA transferase; a malic enzyme; a palate dehydrogenase; a palate oxidoreductase; a pyruvate kinase; and a PEP phosphatase. -3- [00071 In another aspect, provided herein is a method for producing cytosolic acetyl-CoA, comprising culturing a non-naturally occurring eukaryotic organism comprising an acetvl-CoA pathway under conditions and for a sufficient period of time to produce cytosolic acetyl-CoA. In one embodiment, provided herein is a rnethod for producing cytosolic acetyl-CoA, comprising culturing a non-naturally occurring eukaryotic organism comprising an acetyl-CoA pathway, wherein said organism comprises at least one exogenous nucleic acid encoding an acetyl-CoA pathway enzyme expressed in a sufficient amount to produce cytosolic acetyl-CoA in said organism. In certain embodiments, the acetyl-CoA pathway comprises one or more enzymes selected from the group consisting of a citrate synthase; a citrate transporter; a citrate/oxaloacetate transporter; a citrate/malate transporter; an ATP citrate lyase; a citrate lyase; an acetyl-CoA synthetase; an oxaloacetate transporter; a cytosolic palate dehydrogenase; a malate transporter; a mitochondrial malate dehydrogenase; a pyruvate oxidase (acetate forming); an acetyl-CoA ligase or transferase; an acetate kinase; a phosphotransacetylase; a pyruvate decarboxylase; an acetaldehyde dehydrogenase; a pyruvate oxidase (acetyl-phosphate forming); a pyruvate dehydrogenase, a pyruvate:ferredoxin oxidoreductase or pyruvate fonmate lyase; a acetaldehyde dehydrogenase (acylating); a threonine aldolase; a mitochondrial acetylcarnitine transferase; a peroxisomal acetylcarnitine transferase; a cytosolic acetylcarnitine transferase; a mitochondrial acetylcarnitine translocase; and a peroxisomal acetylcarnitine translocase; a PEP carboxylase; a PEP carboxykinase; an oxaloacetate decarboxylase; a malonate semialdehyde dehydrogenase (acetylating); an acetyl-CoA carboxylase; a m alonyl-CoA decarboxylase; an oxaloacetate dehydrogenase; an oxaloacetate oxidoreductase; a malonyl-CoA reductase; a pyruvate carboxylase; a malonate semialdebyde dehydrogenase; a malonyl-CoA synthetase; a malonyl-CoA transferase; a malic enzyme; a malate dehydrogenase; a malate oxidoreductase; a pyruvate kinase; and a PEP phosphatase. [00081 In another aspect, provided herein is a method for increasing acetyl-CoA in the cytosol of a non-naturally occurring eukaryotic organism, comprising culturing a non-naturally occurring eukaryotic organism comprising an acetyl-CoA pathway under conditions and for a sufficient period of time to increase the acetyl-CoA in the cytosol of the organisni. In some embodiments, provided herein is a method for increasing acetyl-CoA in the cytosol of a non-naturally occurring eukaryotic organism, comprising culturing a non-naturally occurring eukaryotic organism -4comprising an acetyl-CoA pathway, wherein said organism comprises at least one exogenous nucleic acid encoding an acetyl-CoA pathway enzyme expressed in a sufficient amount to increase acetvl-CoA in the cytosol of said non-naturally occurring eukaryotic organism. In certain embodiments, the acetyl-CoA pathway comprises one or rnore enzymes selected from the group consisting of a citrate synthase; a citrate transporter; a citrate/oxaloacetate transporter; a citrate/malate transporter; an ATP citrate lyase; a citrate lyase; an acetyl-CoA synthetase; an oxaloacetate transporter; a cytosolic malate dehydrogenase; a malate transporter; a mitochondrial palate dehydrogenase; a pyruvate oxidase (acetate forming); an acetyl-CoA ligase or transferase; an acetate kinase; a phosphotransacetylase; a pyruvate decarboxylase; an acetaldehyde dehydrogenase; a pyruvate oxidase (acetyl-phosphate forming); a pyruvate dehydrogenase, a pyruvate:ferredoxin oxidoreductase or pyruvate formate Iyase; a acetaldehyde dehydrogenase (acylating); a threonine aldolase; a mitochondrial acetylcarnitine transferase; a peroxisomal acetylcarnitine transferase; a cytosolic acetylcarnitine transferase; a mitochondrial acetylearnitine translocase; and a peroxisomal acetylcamitine translocase; a PEP carboxylase; a PEP carboxykinase; an oxaloacetate decarboxylase; a nalonate semialdehyde dehydrogenase (acetylating); an acetyl-CoA carboxylase; a malonyl-CoA decarboxylase; an oxaloacetate dehydrogenase; an oxaloacetate oxidoreductase; a malonyl-CoA reductase; a pyruvate carboxylase; a malonate semialdehyde dehydrogenase; a malonyl-CoA synthetase; a malonyl CoA transferase; a malic enzyme; a malate dehydrogenase; a malate oxidoreductase; a pyruvate kinase; and a PEP phosphatase. [00091 Provided herein are non-naturally occurring eukaryotic organisms and methods thereof to produce and increase the availability of cytosolic acetyl-CoA in the eukaryotic organisms thereof. Also provided herein are non-naturally occurring eukaryotic organisms and methods thereof to produce optimal yields of certain commodity chemicals, such as 1,3-13DO, or other compounds of interest. [00101 In another aspect, provided herein is a non-naturally occurring eukaryotic organism, comprising (1) an acetyl-CoA pathway, wherein said organism comprises at least one exogenous nucleic acid encoding an acetyl-CoA pathway enzyme expressed in a sufficient amount to (i) transport acetyl-CoA front a mitochondrion and/or peroxisome of said organism to the cytosol of -5said organism, (ii) produce acetyl-CoA in the cytoplasm of said organism, and/or (iii) increase acetyl-CoA in the cytosol of said organism, and (2) a 1,343DO pathway, comprising at least one exogenous nucleic acid encoding a 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO. In certain embodiments, (1) the acetyi-CoA pathway comprises one or more enzymes selected from the group consisting of a citrate synthase; a citrate transporter; a citrate/oxaloacetate transporter; a citrate/malate transporter; an ATP citrate yase; a citrate lyase; an acetyl-CoA synthetase; an oxaloacetate transporter; a cytosolic palate dehydrogenase; a malate transporter; a mitochondrial malate dehydrogenase; a pyruvate oxidase (acetate forming); an acetyl-CoA ligase or transferase; an acetate kinase; a phosphotransacetylase; a pyruvate decarboxylase; an acetaldehyde dehydrogenase; a pyruvate oxidase (acetyl-phosphate forming); a pyruvate dehydrogenase, a pyruvate:ferredoxin oxidoreductase or pyruvate formate lyase; a acetaldehyde dehydrogenase (acylating); a threonine aldolase; a mitochondrial acetylcarnitine trans-ferase; a peroxisomal acetylcarnitine transferase; a cytosolic acetylcarnitine transferase; a mitochondrial acetvlearnitine translocase; a peroxisomal acetylearnitine translocase; a PEP carboxylase; a PEP carboxykinase; an oxaloacetate decarboxylase; a malonate semialdehyde dehydrogenase (acetylating); an acetyl-CoA carboxylase; a ialonyl-CoA decarboxylase; an oxaloacetate dehydrogenase; an oxaloacetate oxidoreductase; a malonyl-CoA reductase; a pyruvate carboxylase; a malonate semialdehyde dehydrogenase; a malonyl-CoA synthetase; a malonyl-CoA transferase; a malic enzyme; a malate dehydrogenase; a malate oxidoreductase; a pyruvate kinase; and a PEP phosphatase; and/or (2) the 1,3-BDO pathway comprises one or more enzymes selected from the group consisting of an acetoacetyl-CoA thiolase; an acetyl-CoA carboxylase; an acetoacetyl-CoA synthase; an acetoacetyl-CoA reductase (CoA-dependent, alcohol forming); 3-oxobutyraldehyde reductase (aldehyde reducing); 4-hydroxy,2-butanone reductase; an acetoacetvl-CoA reductase (CoA-dependent, aldehyde forming); a 3 oxobutyraldehyde reductase (ketone reducing); 3-hydroxybutyraldehyde reductase; an acetoacetyl-CoA reductase (ketone reducing); a 3-hydroxybutyryl-CoA reductase (aldehyde forming); a 3-hydroxybutyryl-CoA reductase (alcohol forming); an acetoacetyl-CoA transferase, an acetoacetvl-CoA hydrolase, an acetoacetyl-CoA synthetase, or a phosphotransacetoacetylase and acetoacetate kinase; an acetoacetate reductase; a 3-hydroxybutyryl-CoA transferase, -6hydrolase. or synthetase; a 3-hydroxybutyrate reductase; and a 3-hydroxybutyrate dehydrogenase. [00111 In another aspect, provided herein is a method for producing 1,3-BDO, comprising culturing a non-naturally occurring eukaryotic organism under conditions and for a sufficient period of time to produce the I,3-BDO, wherein the non-naturally occurring eukaryotic organism comprises (1) an acetyl-CoA pathway, and (2) a 1,3-BDO pathway. In certain embodiments, provided herein is a method for producing 1,3-BDO,. comprising culturing a non-naturally occurring eukaryotic organism, comprising an acetyl-CoA pathway, wherein said organism comprises at least one exogenous nucleic acid encoding an acetyl-CoA pathway enzyme expressed in a sufficient amount to (i) transport acetyl-CoA frorn a mitochondrion and/or peroxisome of said organism to the cytosol of said organism, (ii) produce acetyl-CoA in the cytoplasm of said organism, and/or (iii) increase acetyl-CoA in the cytosol of said organism; and/or (2) a 1,3-BDO pathway, comprising at least one exogenous nucleic acid encoding a 1,3 BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO. In certain embodiments, the acetyl-CoA pathway comprises one or more enzymes selected from the group consisting of a citrate synthase; a citrate transporter; a citrate/oxaloacetate transporter; a citrate/malate transporter; an ATP citrate lyase; a citrate lyase; an acetyl-CoA synthetase; an oxaloacetate transporter; a cytosolic malate dehydrogenase; a malate transporter; a mitochondrial malate dehydrogenase; a pyruvate oxidase (acetate forrning); an acetyl-CoA ligase or transferase; an acetate kinase; a phosphotransacetylase; a pyruvate decarboxylase; an acetaldehyde dehydrogenase; a pyruvate oxidase (acetyl-phosphate forrning); a pyruvate dehydrogenase, a pyruvate:ferredoxin oxidoreductase or pyruvate fornate lyase; a acetaldehyde dehydrogenase (acylating); a threonine aldolase; a mitochondrial acetyicarnitine transferase; a peroxisomal acetylcarnitine transferase; a cytosolic acetylearnitine transferase; a mitochondrial acetylearnitine translocase; a peroxisomal acetylcarnitine translocase; a PEP carboxylase; a PEP carboxykinase; an oxaloacetate decarboxylase; a malonate semialdehyde dehydrogenase (acetylating); an acetyl CoA carboxylase; a malonyl-CoA decarboxylase; an oxaloacetate dehydrogenase: an oxaloacetate oxidoreductase; a malonyl-CoA reductase; a pyruvate carboxylase; a malonate semialdehyde dehydrogenase; a malonyl-CoA synthetase; a ialonyl-CoA transferase; a malic enzyme; a nialate dehydrogenase; a rnalate oxidoreductase; a pyruvate kinase; and a PEP 17 phosphatase; and (2) the 1,3-BDO pathway comprises one or more enzymes selected from the group consisting of an acetoacetyl-CoA thiolase; an acetyl-CoA carboxylase; an acetoacetyl CoA synthase; an acetoacetyl-CoA reductase (CoA-dependent, alcohol forming); 3 oxobutyraldehyde reductase (aldehyde reducing); 4-hydroxy,2-butanone reductase; an acetoacetyl-CoA reductase (CoA-dependent, aldehyde forming); a 3-oxobutyraldehyde reductase (ketone reducing); 3-hydroxybutyraldehyde reductase; an acetoacetyl-CoA reductase (ketone reducing); a 3-hydroxybutyrvl-CoA reductase aldehydee forming); a 3-hydroxybutyryl-CoA reductase (alcohol forming); an acetoacetyl-CoA transferase. an acetoacetyl-CoA hydrolase, an acetoacetvl-CoA synthetase, or a phosphotransacetoacetylase and acetoacetate kinase; an acetoacetate reductase; a 3-hydroxybutvryl-CoA transferase, hydrolase, or synthetase; a 3 hydroxybutvrate reductase; and a 3-hyd roxybutyrate dehydrogenase. [00121 In another aspect, provided herein is a non-naturally occurring eukaryotic organism comprising (1) a 1,3-BDO pathway, wherein said organism comprises at least one exogenous nucleic acid encoding a 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO and (2) a deletion or attenuation of one or more enzymes or pathways that utilize one or more precursors and/or intermediates of a 1,3-BDO pathway. In a specific embodiment, the non-naturally occurring eukaryotic organism comprises a deletion or attenuation of a competing pathway that utilizes acetyl-CoA. In a specific embodiment, the non-naturally occurring eukaryotic organism comprises a deletion or attenuation of a 1,3-3DO intermediate byproduct pathway. [00131 In another aspect, provided herein is a non-naturally occurring eukaryotic organism comprising (1) a I ,3-BDO pathway, wherein said organism comprises at least one exogenous nucleic acid encoding a 1 ,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO and (2) a deletion or attenuation of one or more enzymes or pathways that utilize one or more cofactors of a 1,3-13DO pathway. 100141 In another aspect, provided herein is a non-naturally occurring eukaryotic organism comprising a 1,3-BDO pathway, wherein said organism comprises one or more endogenous and/or exogenous nucleic acids encoding an attenuated I .3-BDO pathway enzynie selected from the group consisting of an acetoacetyl-CoA reductase (CoA-dependent, alcohol fonnin a -8oxobutyraldehyde reductase (aldehyde reducing), a 4-hydroxy- 2 -butanone reductase, an acetoacetyl-CoA reductase (CoA-dependent, aldehyde forming), a 3-oxobutyraldehyde reductase (ketone reducing), a 3-hydroxybutyraldehyde reductase, an acetoacetyl-CoA reductase (ketone reducing), a 3-hydroxybutyryl-CoA reductase (aldehyde forming), a 3 -hydroxybutyryl-CoA reductase (alcohol forming), an acetoacetate reductase, 3-hydroxybutyrate reductase, a 3 hydroxybutyrate dehydrogenase and a 3-hydroxybutyraldehyde reductase; and wherein the attenuated 1,3-3DO pathway enzyme is NAPD1-dependent and has lower enzymatic activity as compared to the 1,3-BDO pathway enzyme encoded by an unaltered or wild-type nucleic acid. [00151 In another aspect, provided herein is a non-naturally occurring eukaryotic organism comprising a 1,3-B[DO pathway, wherein said organism one or more endogenous and/or exogenous nucleic acids encoding a 1,3-BDO pathway enzyme selected from the group consisting of an acetoacetyl-CoA reductase (CoA-dependent, alcohol forming), a 3 oxobutyraldehyde reductase (aldehyde reducing), a 4-hydroxy-2-butanone reductase, an acetoacetyl-CoA reductase (CoA-dependent, aldehyde forrning), a 3-oxobutyraldehyde reductase (ketone reducing), a 3-hydroxybutyraldehyde reductase, an acetoacetyl-CoA reductase (ketone reducing), a 3-hydroxybutyryl-CoA reductase (aldehyde forming), a 3-hydroxybutyryl-CoA reductase (alcohol forming), an acetoacetate reductase, 3-hydroxybutyrate reductase, a 3 hydroxybutyrate dehydrogenase and a 3-hydroxybutyraldehyde reductase; wherein at least one nucleic acid has been altered such that the 1,3-13DO pathway enzyme encoded by the nucleic acid has a greater affinity for NADH than the 1,3-BDO pathway enzyme encoded by an unaltered or wild-type nucleic acid. [00161 In another aspect, provided herein is a non-naturally occurring eukaryotic organism comprising a 1 ,3-BDO pathway, wherein said organism comprises one or more endogenous and/or exogenous nucleic acids encoding a 1,3-BDO pathway enzyme selected from the group consisting of an acetoacetyl-CoA reductase (CoA-dependent, alcohol forming), a 3 oxobutyraldehyde reductase (aldehyde reducing), a 4-hydroxy- 2 -butanone reductase, an acetoacetyl-CoA reductase (CoA-dependent, aldehyde forming), a 3-oxobutyraldehyde reductase (ketone reducing), a 3-hydroxybutyraldehyde reductase, an acetoacetyl-CoA reductase (ketone reducing), a 3-hydroxybutyryl-CoA reductase (aIdehyde forming), a 3 -hydroxybutyryl-CoA -9reductase (alcohol forming), an acetoacetate reductase, 3-hydroxybutyrate reductase, a 3 hydroxybutyrate dehydrogenase and a 3-hydroxybutyraldehyde reductase, wherein at least one nucleic acid has been altered such that the 1,3-BDO pathway enzyme encoded by the nucleic acid has a lesser affinity for NADPH than the I,3-BDO pathway enzyme encoded by an unaltered or wild-type nucleic acid. 100171 In another aspect, provided herein is a non-naturally occurring eukaryotic organism comprising: (1) a 1,3-BDO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO; and (2) an acetyl-CoA pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding an acetyl-CoA pathway enzyme expressed in a sufficient amount to increase NADH in the organism; wherein the acetyl-CoA pathway comprises (i.) an NAD-dependent pyruvate dehydrogenase; (ii.) a pyruvate formate lyase and an NAD-dependent format dehydrogenase; (iii.) a pyruvate:ferredoxin oxidoreductase and an NADH:ferredoxin oxidoreductase; (iv.) a pyruvate decarboxylase and an NA D-dependent acylating acetylaldehyde dehydrogenase; (v.) a pyruvate decarboxylase, a IN AD-dependent acylating acetaldehyde dehydrogenase, an acetate kinase, and a phosphotransacetylase; or (vi.) a pyruvate decarboxylase, an NAD-dependent acylating acetaldehyde dehydrogenase, and an acetyl-CoA synthetase. [00181 In another aspect, provided herein is a non-naturally occurring eukaryotic organism comprising: (1) a I,3-BDO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding an NADPH-dependent 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO; and (2) a pentose phosphate pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a pentose phosphate pathway enzyme selected from the group consisting of glucose-6 phosphate dehydrogenase, 6-phosphogiuconolactonase, and 6-phosphogluconate dehydrogenase (decarboxylating). [00191 In another aspect, provided herein is a non-naturally occurring eukaryotic organism comprising: (1) a 1,3-BDO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding an NADP H-dependent I,3-BDO pathway enzyme -10expressed in a sufficient amount to produce 1,3-BDO; and (2) an Entner Doudoroff pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding an Entner Doudoroff pathway enzyme selected from the group consisting of glucose-6 phosphate dehydrogenase, 6-phosphogluconolactonase, phosphogluconate dehydratase, and 2 keto-3-deoxygluconate 6-phosphate aldolase. 100201 In another aspect, provided herein is a non-naturally occurring eukaryotic organism comprising: (1) a 1,3-BDO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a NADPI--dependent 1,3-BD) pathway enzyme expressed in a sufficient amount to produce 1,3-BDO; and (2) an endogenous and/or exogenous nucleic acid encoding a soluble or membrane-bound transhydrogenase, wherein the transhydrogenase is expressed in a sufficient amount to convert NADH to NADPH. 100211 In another aspect, provided herein is a non-naturally occurring eukaryotic organism comprising: (1) a 1,3-BDO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a NADPH-dependent l,3-BDO pathway enzyme expressed in a sufficient amount to produce I 3-BDO; and (2) an endogenous and/or exogenous nucleic acid encoding an NAD1P-dependent phosphorylating or non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase. [00221 In another aspect, provided herein is a non-naturally occurring eukaryotic organism comprising: (1) a 1,3-BDO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a NADPH--dependent l,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO; and (2) an acetyl-CoA pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding an acetyl-CoA pathway enzyme expressed in a sufficient amount to increase NADPH in the organism; wherein the acetyl-CoA pathway comprises (i) an NADP-dependent pyruvate dehydrogenase; (ii) a pyruvate formate lyase and an NADP-dependent formate dehydrogenase; (iii) a pyruvate:ferredoxin oxidoreductase and an NADPIH:ferredoxin oxidoreductase; (iv) a pyruvate decarboxylase and an NADP-dependent acylating acetylaldehyde dehydrogenase; (v) a pyruvate decarboxylase, a NADP-dependent acylating acetaldehyde dehydrogenase, an acetate -11lkinase, and a phosphotransacetylase; or (vi) a pyruvate decarboxylase, an NADP-dependent acylating acetaldehyde dehydrogenase, and an acetyl-CoA synthetase. [00231 In another aspect, provided herein is a non-natu rally occurring eukaryotic organism comprising: (1) a 1,3-BDO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a NADPH-dependent 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO; and (2) one or more endogenous and/or exogenous nucleic acids encoding a NAD(P)H cofactor enzyme selected from the group consisting of phosphorylating or non -phosphorylating glyceraldehyde-3-phosphate dehydrogenase; pyruvate dehydrogenase; formate dehydrogenase; and acylating acetylaldehyde dehydrogenase; wherein the one or more nucleic acids encoding a N AD(P)H cofactor enzyme has been altered such that the NAD(P)H cofactor enzyme encoded by the nucleic acid has a greater affinity for NADPH than the NAD(P)H cofactor enzyme encoded by an unaltered or wild-type nucleic acid. [00241 In another aspect, provided herein is a non-naturally occurring eukaryotic organism comprising: (1) a 1.3-BDO pathway, comprising at least one endogenous and/or exogenous nucleic acid encoding a NADPH dependent 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO; and (2) one or more endogenous and/or exogenous nucleic acids encoding a NAD(P)H cofactor enzyme selected from the group consisting of a phosphorylating or non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase; a pyruvate dehydrogenase; a formate dehydrogenase; and an acylating acetylaldehyde dehydrogenase; wherein the one or more nucleic acids encoding NAD(P)H cofactor enzyme nucleic acid has been altered such that the NAD(P)H cofactor enzyme that it encodes for has a lesser affinity for NADH than the NAD(P)H cofactor enzyme encoded by an unaltered or wild-type nucleic acid. [00251 In another aspect, provided herein is a non-naturally occurring eukarvotic organism comprising a 1,3-BDO pathway, wherein said organism, and wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1 ,3-BDO, and wherein the organism: (i) comprises a disruption in a endogenous and/or exogenous nucleic acid encoding a NADH] dehydrogenase; (ii) expresses an attenuated NADH dehydrogenase; and/or (iii) has lower or no NADH -12dehydrogenase enzymatic activity as compared to a wild-type version of the eukarvotic organism. [00261 In another aspect, provided herein is a non-naturally occurring eukaryonic organism comprising a 1,3-BDO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a 1,3-13DO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO, and wherein the organism: (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a cytochrome oxidase; (ii) expresses an attenuated cytochrome oxidase; and/or (iii.) has lower or no cytochrome oxidase enzymatic activity as compared to a wild-type version of the eukaryotic organism. [00271 In another aspect, provided herein is a non-naturally occurring eukaryotic organism comprising a 1,3-BDO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO, and wherein the organism: (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a glycerol-3-phosphate (G3P) dehydrogenase; (ii) expresses an attenuated G3P dehydrogenase; (iii) has lower or no G3P dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism; and/or (iv) produces lower levels of glycerol as compared to a wild-type version of the eukaryotic organism. [00281 In another aspect, provided herein is a non-naturally occurring eukarvotic organism comprising a 1,3-BDO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a I,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO, and wherein the organism: (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a G3P phosphatase; (ii) expresses an attenuated G3P phosphatase; (iii) has lower or no G3P phosphatase enzymatic activity as compared to a wild-type version of the eukaryotic organism; and/or (iv) produces lower levels of glycerol as compared to a wild-type version of the eukaryotic organism. 100291 In another aspect, provided herein is a non-naturally eukaryotic organism comprising a 1,3-BDO pathway, wherein said organism comprises at least one endogenous and/or exogenous -13nucleic acid encoding a 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-3D0, and wherein the organism: (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a pyruvate decarboxylase; (ii) expresses an attenuated pyruvate decarboxylase; (iii) has lower or no pyruvate decarboxylase enzymatic activity as compared to a wild-type version of the eukarvotic organism; and/or (iv) produces lower levels of ethanol from pyruvate as compared to a wild-type version of the eukaryotic organism. [00301 In another aspect, provided herein is a non-naturally occurring eukaryotic organism comprising a 1,3-13DO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-13DO, and wherein the organism: (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding an ethanol dehydrogenase; (ii) expresses an attenuated ethanol dehydrogenase; (iii) has lower or no ethanol dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism; and/or (iv) produces lower levels of ethanol as compared to a. wild-type version of the eukaryotic organism. [0031] In another aspect, provided herein is a non-naturally eukaryotic organism comprising a 1,3-13DO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a 1,3-BDO pathway enzyme expressed in a sufficient amount to produce I,3-13D0, and wherein the organism: (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a malate dehydrogenase; (ii) expresses an attenuated palate dehydrogenase; (iii) has lower or no palate dehydrogenase enzymatic activity as compared to a wild-type version of the eukarvotic organism; and/or (iv) has an attenuation or blocking of a malate-asparate shuttle, a malate oxaloacetate shuttle, and/or a rnalate-pyruvate shuttle. [00321 In another aspect, provided herein is a non-naturally eukarvotic organism comprising a 1,3-13DO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-13D, and wherein the organism: (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding an acetoacetyl-CoA hydrolase or transferase; (ii) expresses an attenuated acetoacetyl-CoA hydrolase or transferase; and/or (iii) has lower or no acetoacetyl -14- CoA hydrolase or transferase enzymatic activity as compared to a wild-type version of the eukaryotic organism. [00331 In another aspect, provided herein is a non-naturally occurring eukaryonic organism comprising a 1 ,3-BDO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a 1,3-13DO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO, and wherein the organism: (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a 3-hydroxybutyryl-CoA hydrolase or transferase; (ii) expresses an attenuated 3-bydroxybutyryl-CoA hydrolase or transferase; and/or (iii) has lower or no 3-hydroxybutyryl-CoA hydrolase or transferase enzymatic activity as compared to a wild-type version of the eukaryotic organism 100341 In another aspect, provided herein is a non-naturally occurring eukaryotic organism comprising a I,3-BDO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO; and wherein the organism: (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding an acetaldehyde dehydrogenase (acylating); (ii) expresses an attenuated acetaldehyde dehydrogenase (acylating); and/or (iii) has lower or no acetaldehyde dehydrogenase (acylating) enzymatic activity as compared to a wild-type version of the eukaryotic organism. [00351 In another aspect, provided herein is a non-naturally occurring eukarvotic organism comprising a 1 ,3-BDO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a I,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO, and wherein the organism: (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a 3-hydroxybutyraldehyde dehydrogenase; (ii) expresses an attenuated 3-hydroxybutyraldehyde dehydrogenase; and/or (iii) has lower or no 3-hydroxybutyraldehyde dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism. 100361 In another aspect, provided herein is a non-naturally occurring eukaryotic organism comprising a I,3-BDO pathway, wherein said organism comprises at least one endogenous -15and/or exogenous nucleic acid encoding a 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO, and wherein the organism: (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a 3-oxobutyraldehyde dehydrogenase; (ii) expresses an attenuated 3-oxobutyraidehyde dehydrogenase; and/or (iii) has lower or no 3 oxobutyraldehyde dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism. [00371 In another aspect, provided herein is a non-naturally occurring eukaryotic organism comprising a 1,3-BDO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-3DO, and wherein the organism: (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a 1,3-butanediol dehydrogenase; (ii) expresses an attenuated 1,3-butanediol dehydrogenase; and/or (iii) has lower or no 1,3 butanediol dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism [0038] In another aspect, provided herein is a non-naturally occurring eukaryotic organism comprising a 1,3-BDO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-3DO, and wherein the organism: (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding an acetoacetyl-CoA thiolase; (ii) expresses an attenuated acetoacetyl-CoA thiolase; and/or (iii) has lower or no acetoacetyl-CoA thiolase enzymatic activity as compared to a wild-type version of the eukaryotic organism 100391 In another aspect, provided herein is a non-naturally occurring eukaryotic organism comprising a 1,3-BDO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO; and wherein said organism further comprises an endogenous and/or exogenous nucleic acid encoding a I,3-BDO transporter, wherein the nucleic acid encoding the 1,3-BDO transporter is expressed in a sufficient amount for the exportation of 1,3 BDO from the eukaryotic organism. -16- [00401 In another aspect, provided herein is a non-naturally occurring eukaryotic organism comprising a combined rnitochondrial/cytosolic 1,3-BDO pathway, wherein said organism comprises at least endogenous and/or exogenous nucleic acid encoding a combined mitochondrial/cytosolic 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO. In certain embodiments, the combined mitochondrial/cytosolic 1,3-BDO pathway comprises one or more enzymes selected from the group consisting of a mitochondrial acetoacetyl-CoA thiolase; an acetvl-CoA carboxylase; an acetoacetyl-CoA synthase; a mitochondrial acetoacetyl-CoA reductase; a mitochondrial acetoacetyl-CoA hydrolase, transferase or synthetase; a mitochondrial 3-hydroxybutyryl-CoA hydrolase, transferase or synthetase; a mitochondrial. 3-hydroxybutyrate dehydrogenase; an acetoacetate transporter; a 3 hydroxybutyrate transporter; a 3-hvdroxybutyrvl-CoA transferase or synthetase, a cytosolic acetoacetyl-CoA transferase or synthetase; an acetoacetyl-CoA reductase (CoA-dependent, alcohol fonning); a 3-oxobutyraldehyde reductase (aldehyde reducing); a 4-hydroxy-2-butanone reductase; an acetoacetyl-CoA reductase (CoA-dependent, aldehyde forming); a 3 oxobutyra ldehyde reductase (ketone reducing); a 3-hydroxybutyraldehyde reductase; an acetoacetyl-CoA reductase (ketone reducing); a 3-hydroxybutyryl-CoA reductase (aldehyde forming); a 3-hydroxybutyryi-CoA reductase (alcohol forming); an acetoacetate reductase; a 3 hydroxybutyryl-CoA transferase, hydrolase, or synthetas e; a 3-hydroxybutyrate reductase; and a 3-hydroxybutyrate dehydrogenase. 100411 In another aspect, provided herein is a method for producing 1,3-BDO, comprising culturing any one of the non-naturally occurring eukaryotic organisms comprising a 1,3-BDO pathway provided herein under conditions and for a sufficient period of time to produce 1,3 BDO. In certain embodiments, the eukaryotic organism is cultured in a substantially anaerobic culture medium. In other embodiments, the eukaryotic organism is a Crabtree positive organism. 100421 In another aspect, provided herein is a method for selecting an exogenous 1,3-13DO pathway enzyme to be introduced into a non-naturally occurring eukaryotic organism, wherein the exogenous 1,3-13DO pathway enzyme is expressed in a sufficient amount in the organism to produce 1,3-BDO, said method comprising (i.) measuring the activity of at least one 1,3-BDO pathway enzyme that uses NADH as a cofactor; (ii.) measuring the activity of at least 1,31-BDO -17pathway enzyme that uses NADPH as a cofactor; and (iii.) introducing into the organism at least one 1,3-BDO pathway enzyme that has a greater preference for NADH than NADPH as a cofactor as determined in steps 1 and 2. 3. BRIEF DESCRIPIIONS OF THE DRAWINGS [00431 FIG. I shows an exemplary pathway for the production of acetyl-CoA in the cytosol of a eukarvotic organism. [00441 FIG. 2 shows pathways for the production of cytosolic acetyi-CoA from mitochondrial acetyl-CoA using citrate and oxaloacetate transporters. Enzymes are: A) citrate synthase; B) citrate transporter; C) citrate/oxaloacetate transporter; D) ATP citrate lyase; E) citrate lyase; F) acetyl-CoA synthetase or transferase, or acetate kinase and phosphotransacetylase; G) oxaloacetate transporter K) acetate kinase; and L) phosphotransacetylase. [00451 FIG. 3 shows pathways for the production of cytosolic acetyl-CoA from mitochondrial acetyl-CoA using citrate and malate transporters. Enzymes are A) citrate synthase; B) citrate transporter; C) citrate/malate transporter; D) ATP citrate lyase; E) citrate lyase; F) acetyl-CoA synthetase or transferase, or acetate kinase and phosphotransacetylase; H) cytosoiic palate dehydrogenase; I) palate transporter; J) mitochondrial palate dehydrogenase; K) acetate kinase; and L) phosphotransacetylase. [00461 FIG. 4 shows pathways for the biosynthesis of I,3-BDO from acetyl-CoA. The enzymatic transformations shown are carried out by the following enzymes: A) Acetoacetyl-CoA thiolase, 13) Acetoacetyi-CoA reductase (CoA-dependent, alcohol forming), C) 3 oxobutyraldehyde reductase (aldehyde reducing), D) 4-hydroxy-2-butanone reductase, E) Acetoacetyl-CoA reductase (CoA-dependent, aldehyde forming), F) 3-oxobutyraidehyde reductase (ketone reducing), G) 3-hydroxybutyraldehyde reductase, H) Acetoacetyl-CoA reductase (ketone reducing), 1) 3-hydroxybutyryl-Co-A reductase aldehydee forming), J) 3 hydroxybutyryl-CoA reductase (alcohol forming), K) an acetoacetyl-CoA transferase, an acetoacetyl-CoA hydrolase, an acetoacetyl-CoA synthetase, or a phosphotransacetoacetylase and acetoacetate kinase, L) acetoacetate reductase, M) 3-hydroxybutyryi-CoA transferase, hydrolase, -18or synthetase, N) 3-hydroxybutyrate reductase, and 0) 3-hydroxybutyrate dehydrogenase. An alternative to the conversion of acetyl-CoA to acetoacetyl-CoA by acetoacetyl-CoA thiolase (step A) in the 1,3 BDO pathways depicted in FIG. 4 involves the conversion of acetyl-CoA to malonyl-CoA by acetyl-CoA carboxylase, and the conversion of an acetyl-CoA and the malonyl CoA to acetoacetyl-CoA by acetoacetyl-CoA synthetase (not shown; refer to FIG. 7, steps E and F, or FIG. 9). [00471 FIG. 5 shows pathways for the production of cytosolic acetyl-CoA from cytosolic pyruvate. Enzymes are A) pyruvate oxidase (acetate-forming), B) acetyl-CoA synthetase, ligase or transferase, C) acetate kinase, D) phosphotransacetylase, E) pyruvate decarboxylase, F) acetaldehyde dehydrogenase, G) pyruvate oxidase (acetyl-phosphate forming), H) pyruvate dehydrogenase, pyruvate:ferredoxin oxidoreductase or pyruvate formate lyase. I) acetaldehyde dehydrogenase (acylating), and J) threonine aldolase. [00481 FIG. 6 shows pathways for the production of cytosolic acetyl-CoA from mitochondrial or peroxisomal acetyl-CoA. Enzymes are A) mitochondrial acetylcarnitine transferase, B) peroxisonial acetyicarnitine transferase, C) cytosolic acetylcarnitine transferase, D) mitochondrial acetylearnitine translocase, E) perox isomal acetylcarnitine translocase. 100491 FIG. 7 depicts an exemplary 1,3-BDO pathway. A) acetoacetyl-CoA thiolase, B) acetoacetyl-CoA reductase, C) 3-hydroxybutyryl-CoA reductase (aldehyde forming), D) 3 hydroxvbutyraldehyde reductase, E) acetyl-CoA carboxylase, F) acetoacetyl-CoA synthase. G3P is glycerol-3-phosphate. In this pathway, two equivalents of acetyl-CoA are converted to acetoacetyl-CoA by an acetoacetyl-CoA thiolase. Alternatively, acety-CoA is converted to malonyl-CoA by acetyl-CoA carboxylase, and acetoacetyl-CoA is synthesized from acetyl-CoA and malonyl-CoA by acetoacetyl-CoA synthetase. Acetoacetyl-CoA is then reduced to 3 hvdroxvbutvrv-C.oA by 3-hydroxybutyryl-CoA reductase. The 3-hydroxybutyryl-CoA intermediate is further reduced to 3-hydroxybutyraldehyde, and further to 1,3-BDO by 3 hydroxybutyryl-CoA reductase and 3-hydroxybutyraldehyde reductase. The organism can optionally be further engineered to delete one or more of the exemplary byproduct pathways ("X"). -19- [00501 FIG. 8 depicts exemplary combined mitochondrial/cytosolic 1,3-BDO pathways. Pathway enzymes include: A) acetoacetyl-CoA thiolase, B) acetoacetyl-CoA reductase, C) acetoacetyl-CoA hydrolase, transferase or synthetase, D) 3-hydroxybutyryl-CoA hydrolase, transferase or synthetase, E) 3-hydroxybutyrate dehydrogenase, F) acetoacetate transporter, G) 3 hydroxybutyrate transporter, H) 3-hydroxybutyryl-CoA transferase or synthetase, I) acetoacetyl CoA transferase or synthetase, J) acetyl-CoA carboxylase, and K). acetoacetyl-CoA synthase. [00511 FIG. 9 depicts an exemplary pathway for the conversion of acetyl CoA and malonyl CoA to acetoacetyl-CoA by acetoacetyl-CoA synthase. [00521 FIG. 10 depicts exemplary pathways from phosphoenolpyruvate (PEP) and pyruvate to acetyl-CoA and acetoacetyl-CoA. A) PEP carboxylase or PEP carboxykinase, B) oxaloacetate decarboxylase, C) malonate semialdehyde dehydrogenase (acetylating), D) acetyl-CoA carboxylase or malonyl-CoA decarboxylase, E) acetoacetyl-CoA synthase, F) oxaloacetate dehydrogenase or oxaloacetate oxidoreductase, G) malonyl-CoA reductase, HI) pyruvate carboxylase, I) acetoacetyl-CoA thiolase, J) malonate semialdehyde dehydrogenase, K) malonyl CoA synthetase or transferase, L) malic enzyme, M) malate dehydrogenase or oxidoreductase, N) pyruvate kinase or PEP phosphatase. 4. DETAILED DE[SC RI PT ION [0053] Provided herein are non-naturally occurring eukaryotic organisms and methods thereof to produce and increase the availability of cytosolic acetyl-CoA in the eukaryotic organisms thereof Also provided herein are non-naturally occurring eukaryotic organisms and methods thereof to produce commodity chemicals, such as 1.3-BDO, and/or other compounds of interest. 4.1 Definitions [00541 As used herein, the term "non-naturally occurring" when used in reference to a eukaryotic organism provided herein is intended to mean that the eukaryotic organism has at least one genetic alteration not normally found in a naturally occurring strain of the referenced species, including wild-type strains of the referenced species. Genetic alterations include, for example, modifications introducing expressible nucleic acids encoding metabolic polypeptides, other nucleic acid additions, nucleic acid deletions and/or other functional disruption of the -20eukaryotic organism's genetic material. Such modifications include, for example, coding regions and functional fragments thereof, for heterologous, homologous or both heterologous and homologous polypeptides for the referenced species. Additional modifications include, for example, non-coding regulatory regions in which the modifications alter expression of a gene or operon. Exemplary metabolic polypeptides include enzymes or proteins within an acetyl-CoA pathway. [00551 A metabolic modification refers to a biochemical reaction that is altered from its naturally occurring state. Therefore, non-naturally occurring eukaryotic organisms can have genetic modifications to nucleic acids encoding metabolic polypeptides, or functional fragments thereof Exemplary metabolic modifications are disclosed herein. 100561 As used herein, the term "isolated" when used in reference to a eukaryotic organism is intended to mean an organism that is substantially free of at least one component as the referenced eukaryotic organism is found in nature. The term includes a eukaryotic organism that is removed from some or all components as it is found in its natural environment. The term also includes a eukaryotic organism that is removed from some or all components as the eukarvotic organism is found in non-naturally occurring environments. Therefore, an isolated eukaryotic organism is partly or completely separated from other substances as it is found in nature or as it is grown, stored or subsisted in non-naturally occurring environments. Specific examples of isolated eukaryotic organisms include partially pure microbes, substantially pure microbes and microbes cultured in a medium that is non-naturally occurring. [0057] As used herein, the terms "eukaryotic," "eukaryotic organism," or "eukaryote" are intended to refer to any single celled or multi-cellular organism of the taxon Eukarya or Eukaryota. In particular, the terms encompass those organisms whose cells comprise a mitochondrion. The term also includes cell cultures of any species that can be cultured for the increased levels of cytosolic acetyl-CoA. In certain embodiments of the compositions and methods provided herein, the eukaryotic organism is a yeast. 100581 As used herein, the term "CoA"' or "coenzyme A" is intended to mean an organic cofactor or prosthetic group (nonprotein portion of an enzyme) whose presence is required for -21the activity of many enzymes (the apoenzyme) to form an active enzyme system. Coenzyme A functions in certain condensing enzymes, acts in acetyl or other acyl group transfer and in fatty acid synthesis and oxidation, pyruvate oxidation and in other acetylation. [00591 As used herein, the tern "substantially anaerobic" when used in reference to a culture or growth condition is intended to mean that the amount of oxygen is less than about 1 0% of saturation for dissolved oxygen in liquid media. The term also is intended to include sealed chambers of liquid or solid medium maintained with an atmosphere of less than about 1% oxygen. [00601 "Exogenous" as it is used herein is intended to mean that the referenced molecule or the referenced activity is introduced into the host eukaryotic organism. The molecule can be introduced, for example, by introduction of an encoding nucleic acid into the host genetic material such as by integration into a host chromosome or as non-chromosomal genetic material such as a plasmid. Therefore, the term as it is used in reference to expression of an encoding nucleic acid refers to introduction of the encoding nucleic acid in an expressible forn into the eukaryotic organism. When used in reference to a biosynthetic activity, the term refers to an activity that is introduced into the host reference organism. The source can be, for example, a homologous or heterologous encoding nucleic acid that expresses the referenced activity following introduction into the host eukaryotic organism. Therefore, the term "endogenous" refers to a referenced molecule or activity that is present in the host. Similarly, the term when used in reference to expression of an encoding nucleic acid refers to expression of an encoding nucleic acid contained within the eukaryotic organism. The term "heterologous" refers to a molecule or activity derived from a source other than the referenced species whereas "homologous" refers to a molecule or activity derived from the host eukaryotic organism. Accordingly, exogenous expression of an encoding nucleic acid provided herein can utilize either or both a heterologous or homologous encoding nucleic acid. 100611 It is understood that when more than one exogenous nucleic acid is included in a eukaryotic organism that the more than one exogenous nucleic acids refers to the referenced encoding nucleic acid or biochemical activity, as discussed above. It is further understood, as disclosed herein, that such more than one exogenous nucleic acids can be introduced into the -22host eukaryotic organism on separate nucleic acid molecules, on polycistronic nucleic acid molecules, or a combination thereof, and still be considered as more than one exogenous nucleic acid. For example, as disclosed herein a eukaryotic organism can be engineered to express two or more exogenous nucleic acids encoding a. desired pathway enzyme or protein. In the case where two exogenous nucleic acids encoding a desired activity are introduced into a host eukaryotic organism, it is understood that the two exogenous nucleic acids can be introduced as a single nucleic acid, for example, on a single plasmid, on separate plasmids, can be integrated into the host chromosome at a single site or multiple sites, and still be considered as two exogenous nucleic acids. Similarly, it is understood that more than two exogenous nucleic acids can be introduced into a host organism in any desired combination, for example, on a single plasmid, on separate plasmids, can be integrated into the host chromosome at a single site or multiple sites, and still be considered as two or more exogenous nucleic acids, for example three exogenous nucleic acids. Thus, the number of referenced exogenous nucleic acids or biosynthetic activities refers to the number of encoding nucleic acids or the number of biochemical activities, not the number of separate nucleic acids introduced into the host organism. [00621 The non-naturally occurring eukaryotic organisms provided herein can contain stable genetic alterations, which refers to eukaryotic organisms that can be cultured for greater than five generations without loss of the alteration. Generally, stable genetic alterations include modifications that persist greater than 10 generations, particularly stable modifications will persist more than about 25 generations, and more particularly, stable genetic modifications will be greater than 50 generations, including indefinitely. [00631 Those skilled in the art will understand that the genetic alterations, including metabolic modifications exemplified herein, are described with reference to a suitable host organism and their corresponding metabolic reactions or a suitable source organism for desired genetic material such as genes for a desired metabolic pathway. However, given the complete genome sequencing of a wide variety of organisms and the high level of skill in the area of genomics, those skilled in the art will readily be able to apply the teachings and guidance provided herein to essentially all other organisms. For example, the metabolic alterations exemplified herein can readily be applied to other species by incorporating the same or -23analogous encoding nucleic acid from species other than the referenced species. Such genetic alterations include, for example, genetic alterations of species homologs, in general, and in particular, orthologs, paralogs or nonorthologous gene displacements. [00641 An ortholog is a gene or genes that are related by vertical descent and are responsible for substantially the same or identical functions in different organisms. For example, mouse epoxide hydrolase and human epoxide hydrolase can be considered orthologs for the biological function of hydrolysis of epoxides. Genes are related by vertical descent when, for example, they share sequence similarity of sufficient amount to indicate they are homologous, or related by evolution from a common ancestor. Genes can also be considered orthologs if they share three-dimensional structure but not necessarily sequence similarity, of a sufficient amount to indicate that they have evolved from a common ancestor to the extent that the primary sequence similarity is not identifiable, Genes that are orthologous can encode proteins with sequence similarity of about 25% to 100% amino acid sequence identity. Genes encoding proteins sharing an amino acid similarity less that 25% can also be considered to have arisen by vertical descent if their three-dimensional structure also shows similarities. Members of the shrine protease family of enzymes, including tissue plasminogen activator and elastase, are considered to have arisen by vertical descent from a common ancestor. [00651 Orthologs include genes or their encoded gene products that through, for example, evolution, have diverged in structure or overall activity. For example, where one species encodes a gene product exhibiting two functions and where such functions have been separated into distinct genes in a second species, the three genes and their corresponding products are considered to be orthologs. With respect to the metabolic pathways described herein, those skilled in the art will understand that the orthologous gene harboring the metabolic activity to be introduced or disrupted is to be chosen for construction of the non-naturally occurring eukaryotic organism. An example of orthologs exhibiting separable activities is where distinct activities have been separated into distinct gene products between two or more species or within a single species. A specific example is the separation of elastase proteolysis and plasminogen proteolysis, two types of shrine protease activity, into distinct molecules as plasminogen activator and elastase. A second example is the separation of mycoplasma 5-3' exonuclease and -24- Drosophila DNA polymerase III activity. The DNA polymerase from the first species can be considered an ortholog to either or both of the exonuclease or the polymerase from the second species and vice versa. [00661 In contrast, paralogs are homologs related by, for example, duplication followed by evolutionary divergence and have similar or common, but not identical functions. Paralogs can originate or derive from, for example, the same species or from a different species. For example, microsomal epoxide hydrolase (epoxide hydrolase I) and soluble epoxide hydrolase (epoxide hydrolase II) can be considered paralogs because they represent two distinct enzymes, co evolved from a common ancestor, that catalyze distinct reactions and have distinct functions in the same species. Paralogs are proteins from the same species with significant sequence similarity to each other, suggesting that they are homologous, or related through co-evolution from a common ancestor. Groups of paralogous protein families include HipA hornologs, luciferase genes, peptidases, and others. [00671 A nonorthologous gene displacement is a nonorthologous gene from one species that can substitute for a referenced gene function in a different species. Substitution includes, for example, being able to perform substantially the same or a similar function in the species of origin compared to the referenced function in the different species. Although generally, a nonorthologous gene displacement will be identifiable as structurally related to a known gene encoding the referenced function, less structurally related but functionally similar genes and their corresponding gene products nevertheless will still fail within the meaning of the term as it is used herein. Functional similarity requires, for example, at least some structural similarity in the active site or binding region of a nonorthologous gene product cornpared to a gene encoding the function sought to be substituted. Therefore, a nonorthologous gene includes, for example, a paralog or an unrelated gene. [00681 Therefore, in identifying and constructing the non-naturally occurring eukaryotic organisms provided herein having cytosolic acetyl-CoA biosynthetic capability, those skilled in the art will understand with applying the teaching and guidance provided herein to a particular species that the identification of metabolic modifications can include identification and inclusion or inactivation of orthologs. To the extent that paralogs and/or nonorthologous gene displacements are present in the referenced eukaryotic organism that encode an enzyme catalyzing a similar or substantially similar metabolic reaction, those skilled in the art also can utilize these evolutionally related genes. [00691 Orthologs, paralogs and nonoithologous gene displacements can be determined by methods well known to those skilled in the art. For example, inspection of nucleic acid or amino acid sequences for two polypeptides will reveal sequence identity and similarities between the compared sequences. Based on such similarities, one skilled in the art can determine if the similarity is sufficiently high to indicate the proteins are related through evolution from a common ancestor. Algorithms well known to those skilled in the art, such as Align, BLAST, Clustal W and others compare and determine a raw sequence similarity or identity, and also determine the presence or significance of gaps in the sequence which can be assigned a weight or score. Such algorithms also are known in the art and are similarly applicable for determining nucleotide sequence similarity or identity. Parameters for sufficient similarity to determine relatedness are computed based on well known methods for calculating statistical similarity, or the chance of finding a similar match in a random polypeptide, and the significance of the match determined. A computer comparison of two or more sequences can, if desired, also be optimized visually by those skilled in the art. Related gene products or proteins can be expected to have a high similarity, for example, 25% to 100% sequence identity. Proteins that are unrelated can have an identity which is essentially the same as would be expected to occur by chance, if a database of sufficient size is scanned (about 5%). Sequences between 5% and 24% may or may not represent sufficient homology to conclude that the compared sequences are related, Additional statistical analysis to determine the significance of such matches given the size of the data set can be carried out to determine the relevance of these sequences. [00701 Exemplary parameters for determining relatedness of two or more sequences using the BLAST algorithm, for example, can be as set forth below. Briefly, amino acid sequence alignments can be performed using BLASTP version 2.0.8 (Jan-05-1999) and the following parameters: Matrix: 0 B LOSUM62; gap open: 11; gap extension: I; x dropoff: 50; expect: 10.0; wordsize: 3; filter: on. Nucleic acid sequence alignments can be performed using BLASTN version 2.0.6 (Sept-16-1998) and the following parameters: Match: 1; mismatch: -2; gap open: -26- 5; gap extension: 2; x dropoff: 50; expect: 10.0; wordsize: 11; filter: off. Those skilled in the art will know what modifications can be made to the above parameters to either increase or decrease the stringency of the comparison, for example, and determine the relatedness of two or more sequences. 4.2 Eukaryotic Organisms That Utilize Cytosolic Acetyl-CoA [00711 In a first aspect, provided herein is a non-naturally occurring eukaryotic organism comprising an acetyl-CoA pathway, wherein said organism comprises at least one exogenous nucleic acid encoding an acetyl-CoA pathway enzyme expressed in a sufficient amount to (i) transport acetyl-CoA from a mitochondrion and/or peroxisome of said organism to the cytosol of said organism, (ii) produce acetyl-CoA in the cytoplasm of said organism, and/or (iii) increase acetyl-CoA in the cytosol of said organism. In certain embodiments, the acetyl-CoA pathway comprises one or more enzymes selected from the group consisting of a citrate synthase; a citrate transporter; a citrate/oxaloacetate transporter; a citrate/malate transporter; an ATP citrate Ivase; a citrate lyase; an acetyl-CoA synthetase; an oxaloacetate transporter; a cytosolic malate dehydrogenase; a malate transporter; a mitochondrial malate dehydrogenase; a pyruvate oxidase (acetate forming); an acetyi-CoA ligase or transferase; an acetate kinase; a phosphotransacetylase; a pyruvate decarboxylase; an acetaldehyde dehydrogenase; a pyruvate oxidase (acetyl-phosphate forming); a pyruvate dehydrogenase, a pyruvate:ferredoxin oxidoreductase or pyruvate formate lyase; a acetaldehyde dehydrogenase (acylating); a threonine aldolase; a mitochondrial acetvlcarnitine transferase; a peroxisomal acetylcarnitine transferase; a cytosolic acetylcarnitine transferase; a mitochondrial acetylcarnitine translocase; a peroxisomal acetylcarnitine translocase; a PEP carboxylase; a PEP carboxykinase; an oxaloacetate decarboxylase; a malonate semialdehyde dehydrogenase (acetylating); an acetyl-CoA carboxylase; a malonyl-CoA decarboxylase; an oxaloacetate dehydrogenase; an oxaloacetate oxidoreductase; a malonyl-CoA reductase; a pyruvate carboxylase; a malonate semialdehyde dehydrogenase; a malonyl-CoA synthetase; a malonyl-CoA transferase; a rnalic enzyme; a malate dehydrogenase; a malate oxidoreductase; a pyruvate kinase; and a PEP phosphatase. Such organisms would advantageously allow for the production of cytosolic acetyl-CoA, which can then be used by the organism to produce compounds of interest, for example, I,3-BDO, using a cytosolic production pathway.

[00721 In one embodiment, provided herein is a non-naturally occurring eukaryotic organism comprising an acetyl-CoA pathway, wherein said organism comprises at least one exogenous nucleic acid encoding an acetyl-CoA pathway enzyme expressed in a sufficient amount to transport acetyl-CoA from a mitochondrion of said organism to the cytosol of said organism, In another embodiment, provided herein is a non-naturally occurring eukarvotic organism comprising an acetyl-Co A pathway, wherein said organism comprises at least one exogenous nucleic acid encoding an acetyl-CoA pathway enzyme expressed in a sufficient amount to transport acetyl-CoA from a peroxisome of said organism to the cytosol of said organism. In one embodiment, provided herein is a non-naturally occurring eukaryotic organism comprising an acetyl-CoA pathway, wherein said organism comprises at least one exogenous nucleic acid encoding an acetyl-CoA pathway enzyme expressed in a sufficient amount to produce acetyl CoA in the cytoplasm of said organism. In another embodiment, provided herein is a non naturally occurring eukarvotic organism comprising an acetyl-CoA pathway, wherein said organism comprises at least one exogenous nucleic acid encoding an acetyl-CoA pathway enzyme expressed in a sufficient amount to increase acetyl-CoA in the cytosol of said organism. In other embodiments, provided herein is a non-naturally occurring eukaryotic organism comprising an acetyl-CoA pathway, wherein said organism comprises at least one exogenous nucleic acid encoding an acetyl-CoA pathway enzyme expressed in a sufficient amount to transport acetyl-CoA from a mitochondrion and produce acetyl-CoA in the cytoplasm of said organism. In another embodiment, provided herein is a non-naturally occurring eukaryotic organism comprising an acetyl-CoA pathway, wherein said organism comprises at least one exogenous nucleic acid encoding an acetyl-CoA pathway enzyme expressed in a sufficient amount to transport acetyl-CoA from a peroxisome of said organism to the cytosol of said organism and produce acetyl-CoA in the cytoplasm of said organism. In other embodiments, provided herein is a non-naturally occurring eukaryotic organism comprising an acetyl-CoA pathway, wherein said organism comprises at least one exogenous nucleic acid encoding an acetyl-CoA pathway enzyme expressed in a sufficient amount to transport acetyl-CoA from a mitochondrion and increase acetyl-CoA in the cytoplasm of said organism. in another embodiment, provided herein is a nor-naturally occurring eukaryotic organism comprising an acetyl-CoA pathway, wherein said organism comprises at least one exogenous nucleic acid -28encoding an acetyl-CoA pathway enzyme expressed in a sufficient amount to increase acetyl CoA from a peroxisome and increase acetvl-CoA in the cytosol of said organism. [00731 In a second aspect, provided herein is a method for transporting acetyl-CoA from a mitochondrion and/or peroxisome to a cytosol of a non-naturally occurring eukarvotic organism, comprising culturing a non-naturally occurring eukaryotic organism comprising an acetyl-CoA pathway under conditions and for a sufficient period of time to transport the acetyl-CoA from a mitochondrion and/or peroxisome to a cytosol of the non-naturally occurring eukaryotic organism. In one embodiment, provided herein is a method for transporting acetyl-CoA from a mitochondrion to a cytosol of a non-naturally occurring eukaryotic organism, comprising culturing a non-naturally occurring eukaryotic organism comprising an acetyl-CoA pathway under conditions and for a sufficient period of time to transport the acetyl-CoA from a mitochondrion to a cytosol of the non-naturally occurring eukaryotic organism.In another embodiment, provided herein is a method for transporting acetyl-CoA from a peroxisome to a cytosol of a non-naturally occurring eukaryotic organism, comprising culturing a non-naturally occurring eukarvotic organism comprising an acetyl-CoA pathway under conditions and for a sufficient period of time to transport the acetyl-CoA from a peroxisome to a cytosol of the non naturally occurring eukaryotic organism. In certain embodiments, the acetyl-CoA pathway comprises one or more enzymes selected from the group consisting of a citrate synthase; a citrate transporter; a citrate/oxaloacetate transporter; a citrate/malate transporter; an ATP citrate lvase; a citrate lyase; an acetyl-CoA synthetase; an oxaloacetate transporter a cytosolic malate dehydrogenase; a malate transporter; a mitochondrial malate dehydrogenase; a pyruvate oxidase (acetate forming); an acetyl-CoA ligase or transferase; an acetate kinase; a phosphotransacetylase; a pyruvate decarboxylase; an acetaldehyde dehydrogenase; a pyruvate oxidase (acetyl-phosphate forming); a pyruvate dehydrogenase, a pyruvate:ferredoxin oxidoreductase or pyruvate formate lyase; a acetaldehyde dehydrogenase (acylating); a threonine aldolase; a mitochondrial acetylcarnitine transferase; a peroxisomal acetylcarnitine transferase; a cytosolic acetylcarmitine transferase; a mitochondrial acetylcarnitine translocase; a peroxisomal acetylearnitine translocase; a PEP carboxylase; a PEP carboxykinase; an oxaloacetate decarboxylase; a malonate semialdehyde dehydrogenase (acetylating); an acetyl-CoA carboxylase; a malonyl-CoA decarboxylase; an oxaloacetate dehydrogenase; an oxaloacetate -290oxidoreductase; a malonyl-CoA reductase; a pyruvate carboxylase; a malonate semialdehyde dehydrogenase; a malonyl-CoA synthetase; a malonyl-CoA transferase; a malic enzyme; a malate dehydrogenase; a malate oxidoreductase; a pyruvate kinase; and a PEP phosphatase. [00741 In another embodiment, provided herein is a method for transporting acetyl-CoA from a mitochondrion to a cytosol of a non-naturally occurring eukaryotic organism, comprising culturing a non-naturally occurring eukaryotic organism comprising an acetyl-CoA pathway, wherein said organism comprises at least one exogenous nucleic acid encoding an acetyl-CoA pathway enzyme expressed in a sufficient amount to transport acetyl-CoA from a mitochondrion of said organism to the cytosol of said organism. In certain embodiments, the acetyl-CoA pathway comprises one or more enzymes selected from the group consisting of a citrate synthase; a citrate transporter; a citrate/oxaloacetate transporter; a citrate/malate transporter; an ATP citrate lyase; a citrate lyase; an acetyl-CoA synthetase; an oxaloacetate transporter; a cytosolic malate dehydrogenase; a malate transporter; a mitochondrial malate dehydrogenase; a pyruvate oxidase (acetate forming); ai acetyl-CoA ligase or transferase; an acetate kinase; a phosphotransacetylase; a pyruvate decarboxylase; an acetaldehyde dehydrogenase; a pyruvate oxidase (acetyl-phosphate forming); a pyruvate dehydrogenase, a pyruvate:ferredoxin oxidoreductase or pyruvate formate lyase; a acetaldehyde dehydrogenase (acylating); a threonine aldolase; a mitochondrial acetylcarnitine transferase; a cytosolic acetylcarnitine transferase; and a mitochondrial acetylcarnitine translocase. [0075] In some embodiments, provided herein is a method for transporting acetyl-CoA from a peroxisome to a cytosol of a non-naturally occurring eukaryotic organism, comprising culturing said non-naturally occurring eukaryotic organisin comprising an acetyl-CoA pathway, wherein said organism comprises at least one exogenous nucleic acid encoding an acetyl-CoA pathway enzyme expressed in a sufficient amount to transport acetyl-CoA from a peroxisome of said organism to the cytosol of said organism. In certain embodiments, the acetyl-CoA pathway comprises one or more enzymes selected from the group consisting of a peroxisomal acetylcarnitine transferase and a perox isomal acetylcarnitine translocase. [00761 In a third aspect, provided herein is a method for producing cytosolic acetyl-CoA, comprising culturing a non-naturally occurring eukaryotic organism comprising an acetyl-CoA -30pathway under conditions and for a sufficient period of time to produce cytosolic acetyl-CoA. In one embodiment, said organism comprises at least one exogenous nucleic acid encoding an acetyl-CoA pathway enzyme expressed in a sufficient amount to produce cytosolic acetyl-CoA in said organism. In certain embodiments, the acetyl-CoA pathway comprises one or more enzymes selected from the group consisting of a citrate synthase; a citrate transporter; a citrate/oxaloacetate transporter; a citrate/malate transporter; an ATP citrate lyase; a citrate lyase; an acetyl-CoA synthetase; an oxaloacetate transporter; a cytosolic malate dehydrogenase; a malate transporter; a mitochondrial malate dehydrogenase; a pyruvate oxidase (acetate forming); an acetyl-CoA ligase or transferase; an acetate kinase; a phosphotransacetylase; a pyruvate decarboxylase; an acetaldehyde dehydrogenase; a pyruvate oxidase (acetyl-phosphate forming); a pyruvate dehydrogenase, a pyruvate:ferredoxin oxidoreductase or pyruvate formate lyase; a acetaldehyde dehydrogenase (acylating); a threonine aldolase; a mitochondrial acetylcarnitine trans-ferase; a peroxisomal acetylcarnitine transferase; a cytosolic acetylcarnitine transferase; a mitochondrial acetvlcarnitine translocase; a peroxisomal acetylcarnitine translocase; a PEP carboxylase; a PEP carboxykinase; an oxaloacetate decarboxylase; a malonate sernialdehyde dehydrogenase (acetylating); an acetyl-CoA carboxylase; a malonyl-CoA decarboxylase; an oxaloacetate dehydrogenase; an oxaloacetate oxidoreductase; a malonyl-CoA reductase; a pyruvate carboxylase; a malonate semialdehyde dehydrogenase; a malonyl-CoA synthetase; a malonyl-CoA transferase; a malic enzyme; a malate dehydrogenase; a malate oxidoreductase; a pyruvate kinase; and a PEP phosphatase. [00771 In a fourth aspect, provided herein is a method for increasing acetyl-CoA in the cytosol of a non-naturally occurring eukaryotic organism, comprising culturing a non-naturally occurring eukaryotic organism comprising an acetyl-CoA pathway under conditions and for a sufficient period of time to increase the acetyl-CoA in the cytosol of the organism. In some embodiments, the organism comprises at least one exogenous nucleic acid encoding an acetyl CoA pathway enzyme expressed in a sufficient amount to increase acetyl-CoA in the cytosol of said non-naturally occurring eukaryotic organism. In certain embodiments, the acetyl-CoA pathway comprises one or more enzymes selected from the group consisting of a citrate synthase; a citrate transporter; a citrate/oxaloacetate transporter; a citrate/malate transporter; an ATP citrate lyase; a citrate lyase; an acetyl-CoA synthetase; an oxaloacetate transporter; a -31cvtosolic palate dehydrogenase; a malate transporter; a mitochondrial palate dehydrogenase; a pyruvate oxidase (acetate forming); an acetyl-CoA ligase or transferase; an acetate kinase; a phosphotransacetylase; a pyruvate decarboxylase; an acetaldehyde dehydrogenase; a pyruvate oxidase (acetyl-phosphate forrning); a pyruvate dehydrogenase, a pyruvate: ferredox in oxidoreductase or pyruvate formate lyase; a acetaldehyde dehydrogenase (acylating); a threonine aldola se; a mitochondrial acetyicarnitine transferase; a peroxisornal acetylcarnitine transferase; a cytosolic acetylcarnitine transferase; a mitochondrial acetyicarnitine translocase; a peroxisomal acetylcamitine translocase; a PEP carboxylase; a PEP carboxykinase; an oxaloacetate decarboxylase; a malonate semialdehyde dehydrogenase (acetylating); an acetyl-CoA carboxylase; a malonyl-CoA decarboxylase; an oxaloacetate dehydrogenase; an oxaloacetate oxidoreductase; a malonyl-CoA reductase; a pyruvate carboxylase; a malonate semialdehyde dehydrogenase; a malonyl-CoA synthetase; a malonyl-CoA transferase: a malic enzyme: a palate dehydrogenase; a malate oxidoreductase; a pyruvate kinase; and a PEP phosphatase. [0078] In many eukaryotic organisms, acetyl-CoA is mainly synthesized by pyruvate dehydrogenase in the mitochondrion (FIG. 1). A mechanism for exporting acetyl-COA from the mitochondrion to the cytosol can enable deployment of, for example, a cytosolic 1,3-BDO production pathway that originates from acetyl-CoA, Exemplary mechanisms for exporting acetvl-CoA include those depicted in FIGS. 2, 3 and 8, which can involve forming citrate from acetyl-CoA and oxaloacetate in the mitochondrion, exporting the citrate from the mitochondrion to the cytosol, and converting the citrate to oxaloacetate and either acetate or acetyl-CoA. In certain embodiments, provided herein are methods for engineering a eukaryotic organism to increase its availability of cytosolic acetyl-CoA by introducing enzymes capable of carrying out the transformations depicted in any one of FIGS. 2, 3 and 8. Exemplary enzymes capable of carrying out the required transformations are also disclosed herein. 100791 Acetyl-CoA localized in cellular organelles, such as peroxisomes and mitochondria, can also be exported into the cytosol by the aid of a carrier protein, such as carnitine or other acetyl carriers. In some embodiments of the composition and methods provided herein, the translocation of acetyl units across organellar membranes, such as a mitochondrial or peroxisomal membrane, utilizes a carrier molecule or acyl-CoA transporter. An exemplary -32acetyl carrier molecule is camitine. Other exemplary acetyl carrier molecules or transporters include glutamate, pyruvate, im idazole and glucosamine. [00801 A mechanism for exporting acetyl-CoA localized in cellular organelles such as peroxisomes and mitochondria to the cytosol using a carrier protein could enable deployment of, for example, a cytosolic 1,3-BDO production pathway that originates from acetyl-CoA. Exemplary acetyicarnitine translocation pathways are depicted in FIG. 6. In one pathway, mitochondrial acetyl-CoA is converted to acetylearnitine by a mitochondrial acetylcamitine transferase. Mitochondrial acetylcarnitine can then be translocated across the mitochondrial membrane into the cytosol by a mitochondrial acetylcarnitine translocase, and then converted to cytosolic acetyl-CoA by a cytosolic acetylcarnitine transferase. In another pathway, peroxisornal acetyl-CoA is converted to acetylcamitine by a peroxisomal acetylcaritine transferase. Peroxisomal acetylcarnitine can then be translocated across the peroxisomal membrane into the cytosol by a peroxisomal acetylcamitine translocase, and then converted to cytosolic acetyl-CoA by a cytosolic acetylcarnitine transferase. [0081] Pathways for the conversion of cytosolic pyruvate and threonine to cytosolic acetyl CoA could enable deployment of, for example, a cytosolic 1,3-3DO production pathway that originates from acetyl-CoA. In addition to several known pathways, FIG. 5 depicts four novel exemplary pathways for converting cytosolic pyruvate to cytosolic acetyl-CoA. In one pathway, pyruvate is converted to acetate by pyruvate oxidase (acetate forming). Acetate is subsequently converted to acetyi-CoA either directly, by acetyl-CoA synthetase, ligase or transferase, or indirectly via an acetyl-phosphate intermediate. In an alternate route, pyruvate is decarboxylated to acetaidehyde by pyruvate decarboxylase. An acetaldehyde dehydrogenase oxidizes acetaldehyde to acetate. Acetate is then converted to acetyl-CoA by acetate kinase and phosphotransacetylase. In yet another route, pyruvate is oxidized to acetylphosphate by pyruvate oxidase (acetyl-phosphate forming). Phosphotransacetylase then converts acetylphopshate to acetyl-CoA. Exemplary enzymes capable of carrying out the required transformations are also disclosed herein. [00821 Pathways for the conversion of cytosolic phosphoenolpyruvate (PEP) and pyruvate to cytosolic acetvl-CoA could also enable deployment of, for example, a cytosolic 1,3-BDO -33:,production pathway from acetyl-CoA. FIG. 10 depicts twelve exemplary pathways for converting cytosolic PEP and pyruvate to cytosolic acetyl-CoA. In one pathway, PEP carboxylase or PEP carboxykinase converts PEP to oxaloacetate (step A); oxaloacetate decarboxylase converts the oxaloacetate to malonate (step B); and malonate semialdehyde dehydrogenase (acetylating) converts the malonate semialdehyde to acetyl-CoA (step C). In another pathway pyruvate kinase or PEP phosphatase converts PEP to pyruvate (step N); pyruvate carboxylase converts the pyruvate to (step [H); oxaloacetate decarboxylase converts the oxaloacetate to malonate (step B); and malonate semialdehyde dehydrogenase (acetylating) converts the nialonate semialdehyde to acetyl-CoA (step C). In another pathway pyruvate kinase or PEP phosphatase converts PEP to pyruvate (step N); malic enzyme converts the pyruvate to malate (step L); malate dehydrogenase or oxidoreductase converts the malate to oxaloacetate (step M); oxaloacetate decarboxylase converts the oxaloacetate to malonate (step B); and malonate seniialdehyde dehydrogenase (acetylating) converts the malonate semialdehyde to acetyl-CoA (step C). in another pathway, PEP carboxylase or PEP carboxykinase converts PEP to oxaloacetate (step A); oxaloacetate decarboxylase converts the oxaloacetate to malonate semialdehyde (step B); rnalonyl-CoA reductase converts the malonate semialdehyde to malonyl CoA (step G); and malonyl-CoA decarboxylase converts the malonyl-CoA to acetyl-CoA (step (D) In another pathway, pyruvate kinase or PEP phosphatase converts PEP to pyruvate (step N); pyruvate carboxylase converts the pyruvate to oxaloacetate (step H); (oxaloacetate decarboxylase converts the oxaloacetate to nialonate semialdehyde (step B); malonyl-CoA reductase converts the malonate semialdehyde to malonyl-CoA (step G); and malonyl-CoA decarboxylase converts the malonyl-CoA to acetyl-CoA (step (D). In another pathway. pyuvate kinase or PEP phosphatase converts PEP to pyruvate (step N); malic enzyme converts the pyruvate to malate (step L.) malate dehydrogenase or oxidoreductase converts the malate to oxaloacetate (step M); oxaloacetate decarboxylase converts the oxaloacetate to malonate semialdehyde (step B); malonyl-CoA reductase converts the malonate semialdehyde to malonyl CoA (step G); and malonyl-CoA decarboxylase converts the malonyl-CoA to acetyl-CoA (step (D). In another pathway, PEP carboxylase or PEP carboxykinase converts PEP to oxaloacetate (step A); oxaloacetate decarboxylase converts the oxaloacetate to malonate seniialdehyde (step B); malonate semialdehyde dehydrogenase converts the malonate semialdehyde to malonate -34-- (step J); malonyl-CoA synthetase or transferase converts the malonate to malonyl-CoA (step K); and malonyl-CoA decarboxylase converts the malonyl-CoA to acetyl-CoA (step D). In another pathway, pyruvate kinase or PEP phosphatase converts PEP to pyruvate (step N); pyruvate carboxylase converts the pyruvate to oxaloacetate (step -1); oxaloacetate decarboxylase converts the oxaloacetate to malonate sernialdehyde (step B); malonate semialdehyde dehydrogenase converts the malonate setnialdehyde to malonate (step J); malonyl-CoA synthetase or transferase converts the malonate to malonyl-CoA (step K); and malony]-CoA decarboxylase converts the malonyl-CoA to acetyl-CoA (step D). In another pathway, pyruvate kinase or PEP phosphatase converts PEP to pyruvate (step N); malic enzyme converts the pyruvate to palate (step L); malate dehydrogenase or oxidoreductase converts the malate to oxaloacetate (step M); oxaloacetate decarboxylase converts the oxaloacetate to malonate semialdehyde (step B): malonate semialdehyde dehydrogenase converts the malonate sernialdehyde to malonate (step J); malonyl-CoA synthetase or transferase converts the malonate to nalonyl-CoA (step K); and malonyl-CoA decarboxylase converts the malonyl-CoA to acetyl-CoA (step D). In another pathway, PEP carboxylase or PEP carboxykinase converts PEP to oxaloacetate (step A); oxaloacetate dehydrogenase or oxaloacetate oxidoreductase converts the oxaloacetate to malonyl-CoA (step F); and malonyl-CoA decarboxylase converts the malonyl-CoA to acetyl CoA (step D). In another pathway, pyruvate kinase or PEP phosphatase converts PEP to pyruvate (step N); pyruvate carboxylase converts the pyruvate to oxaloacetate (step H); oxaloacetate dehydrogenase or oxaloacetate oxidoreductase converts the oxaloacetate to rnalonyl-CoA (step F); and rnalonyl-CoA decarboxylase converts the malonyl-CoA to acetyl CoA (step D). In another pathway, pyruvate kinase or PEP phosphatase converts PEP to pyruvate (step N); malic enzyme converts the pyruvate to malate (step L); malate dehydrogenase or oxidoreductase converts the malate to oxaloacetate (step M); oxaloacetate dehydrogenase or oxaloacetate oxidoreductase converts the oxaloacetate to malonyl-CoA (step F); and malonyl CoA decarboxylase converts the malonyl-CoA to acetyl-CoA (step D). [00831 In certain embodiments, any pathway (e.g., an acetyl-CoA and/or 1,3-BDO pathway) provided herein further comprises the conversion of acetyl-CoA to acetoacetyl-CoA, e.g., as exemplified in FIG. 4, 7 or 10. In some embodiments, the pathway comprises acetoacetyl-CoA thiolase, which converts acetyl-CoA to acetoacetyl-CoA (FIG. 4, step A; FIG. 7, step A; FIG. 10, -35step I). In another embodiment, the pathway comprises acetyl-CoA carboxylase, which converts acetyl-CoA to malonyl-CoA (FIG. 7, step E; FIG. 10, step D); acetoacetyl-CoA synthase, which converts malonyl-CoA and acetyl-CoA to acetoacetyl-CoA (FG. 7, step F; FIG. 10, step E). [00841 In certain embodiments, non-naturally occurring eukaryotic organisms provided herein express genes encoding an acetyl-CoA pathway for the production of cytosolic acetyl-CoA. In some embodiments, successful engineering of an acetyl CoA pathway entails identifying an appropriate set of enzymes with sufficient activity and specificity, cloning their corresponding genes into a production host, optimizing culture conditions for the conversion of mitochondrial acetyl-CoA to cytosolic acetyl-CoA. and assaying for the production or increase in levels of cytosolic acetyl-CoA following exportation. 100851 The production of cytosolic acetyl-CoA from mitochondrial or peroxisomal acetyl CoA can be accomplished by a number of pathways, for example, in about two to five enzymatic steps. In one exemplary pathway, mitochondrial acetyl-CoA and oxaloacetate are combined into citrate by a citrate synthase and exported out of the mitochondrion by a citrate or citrate/oxaloacetate transporter (see, e.g., FIG. 2). Enzymatic conversion of the citrate in the cytosol results in cytosolic acetyl-CoA and oxaloacetate. The cytosolic oxaloacetate can then optionally be transported back into the mitochondrion by an oxaloacetate transporter and/or a citrate/oxaloacetate transporter. In another exemplary pathway, the cytosolic oxaloacetate is first enzymatically converted into malate in the cytosol and then optionally transferred into the mitochondrion by a palate transporter and/or a malate/citrate transporter (see, e.g., FIG. 3). Mitochondrial malate can then be converted into oxaloacetate with a mitochondrial malate dehydrogena se. In another exemplary pathway, mitochondrial acetyl-CoA is converted to acetylcarnitine by a mitochondrial acetylcarnitine transferase. Mitochondrial acetylcarnitine can then be translocated across the mitochondrial membrane into the cytosol by a mitochondrial acetyicarnitine translocase, and then converted to cytosolic acetyl-CoA by a cytosolic acetylcamitine transferase. In yet another exemplary pathway, peroxisomal acetyl-CoA is converted to acetylcarnitine by a peroxisomal acetylcarnitine transferase. Peroxisomal acetylcarnitine can then be translocated across the peroxisomal membrane into the cytosol by a -36peroxisomal acetylcamitine translocase, and then converted to cytosolic acetyl-CoA by a cytosolic acetylcarnitine transferase. [00861 The production of cytosolic acetyl-CoA from cytosolic pyruvate can be accomplished by a number of pathways, for example, in about two to four enzymatic steps, and exemplary pathways are depicted in FIG. 5. In one pathway, pyruvate is converted to acetate by pyruvate oxidase (acetate forming). Acetate is subsequently converted to acetyl-CoA either directly, by acctyl-CoA svnthetase, ligase or transferase, or indirectly via an acetyl-phosphate intermediate. In an alternate pathway, pyruvate is decarboxylated to acetaldehyde by pyruvate decarboxylase. An acetaldehyde dehydrogenase oxidizes acetaldehyde to acetate. Acetate is then converted to acetyl-CoA by acetate kinase and phosphotransacetylase. In yet another route, pyruvate is oxidized to acetylphosphate by pyruvate oxidase (acetyl-phosphate foning). Phosphotransacetylase then converts acetylphopshate to acetyl-CoA. Other exemplary pathways for the conversion of cytosolic pyruvate to acetyl-CoA are depicted in FIG. 10. [00871 As discussed above, methods for the conversion of mitochondrial acetyl-CoA to cytosolic acetyl-CoA and increasing the levels of cytosolic acetyl-CoA within a eukaryotic organism would allow for the cytosolic production of several compounds of industrial interest, including 1.3-BDO, via a cytosolic production pathway that uses cytosolic acetyl-CoA as a starting material. In certain embodiments, the organisms provided herein further comprise a biosynthetic pathway for the production of a compound using cytosolic acetyl-CoA as a starting material. In certain embodiments, the compound is 1,3-13DO. [0088] Microorganisms can be engineered to produce several compounds of industrial interest using acetyl-CoA, including 1,3-BDO. Thus, provided herein are non-naturally occurring eukaryotic organisms that can be engineered to produce the commodity chemicals, such as 1,3 butanediol. 1,3-BDO is a four carbon diol traditionally produced from acetylene via its hydration. The resulting acetaldehyde is then converted to 3-hydroxybutyraldehdye which is subsequently reduced to form 1,3-B DO. In more recent years, acetylene has been replaced by the less expensive ethylene as a source of acetaldehyde. 1,3-BDO is commonly used as an organic solvent for food flavoring agents. It is also used as a co-monomer for polyurethane and polyester resins and is widely employed as a hypoglycaemic agent. Optically active 1,3-BDO is a useful starting material for the synthesis of biologically active compounds and liquid crystals. A substantial commercial use of 1,3-3DO is subsequent dehydration to afford 1,3-butadiene (ichikawa et al., J. of Molecular Catalvsis A-Chemical, 256:106-112 (2006); ichikawa et al., J. of Mb/ecular Catalysis A-Chemical. 231:181-189 (2005)), a 25 billion lb/yr petrochemical used to manufacture synthetic rubbers (e.g., tires), latex, and resins. The reliance on petroleum based feedstocks for production of 1,3-BDO warrants the development of alternative routes to producing 1,3-BDO and butadiene using renewable feedstocks. [0089] FIG. 4 depicts various exemplary pathways using acetyl-CoA as the starting material that can be used to produce 1,3-BDO from acetyl-CoA. In certain embodiments, the acetoacetyl CoA depicted in the 1.3-13DO pathway(s) of FIG. 4 is synthesized from acetyl-CoA and malonyl-CoA by acetoacetyl-CoA synthetase, for example, as depicted in FIG. 7 (steps E and F) or FIG. 9, wherein acetyl-CoA is converted to malonyl-CoA by acetyl-CoA carboxylase, and acetoacetyl-CoA is synthesized from acetyl-CoA and malonyl-CoA by acetoacetyl-CoA synthetase. [0090] 1 ,3-BD0 production in the cytosol relies on the native cell machinery to provide the necessary precursors. As shown in FIG. 4, acetyl CoA can provide a carbon precursor for the production of 1,3-BDO. Thus, acetyl-CoA pathways that are capable of producing high concentrations of cytosolic acetyl-CoA are desirable for enabling deployment of a cytosolic 1,3 BDO production pathway that originates from acetyl-CoA. [00911 In certain acetyl-CoA pathways provided herein, acetyl-CoA is synthesized in the cytosol from a pyruvate or threonine precursor (FIG. 5). In other acetyl-CoA pathways provided herein, acetyl-CoA is synthesized in the cytosol from phosphoenolpyruvate (PEP) or pyruvate (FIG. 10). In other acetyl-CoA pathways provided herein, acetyl-CoA is synthesized in cellular compartments and transported to the cytosol, either directly or indirectly. One exemplary mechanism for transporting acetyl units from mitochondria or peroxisomes to the cytosol is the carnitine shuttle (FIG. 6). Another exemplary mechanism involves converting mitochondrial acetyl-CoA to a metabolic intermediate such as citrate or citramalate, transporting that intermediate to the cytosol, and then regenerating the acetyl-CoA (see FIGS. 2, 3 and 8). -38- Exemplary acetyl-CoA pathways and corresponding enzymes are describe in further detail below and in Examples 1-111. [00921 Thus, in another aspect. provided herein is a non-naturally occurring eukaryotic organism, comprising (1) an acetyl-CoA pathway, wherein said organism comprises at least one exogenous nucleic acid encoding an acetyl-CoA pathway enzyme expressed in a sufficient amount to (i) transport acetyl-CoA from a mitochondrion and/or peroxisome of said organism to the cytosol of said organism, (ii) produce acetyl-CoA in the cytoplasm of said organism, and/or (iii) increase acetvl-CoA in the cytosol of said organism, and (2) a 1,3-13DO pathway, comprising at least one exogenous nucleic acid encoding a 1,3-BDO pathway enzyme expressed in a sufficient aniount to produce 1,3-BDO. In certain embodiments, (1) the acetvl-CoA pathway comprises one or more enzymes selected from the group consisting of a citrate synthase; a citrate transporter; a citrate/oxaloacetate transporter; a citrate/nalate transporter; an ATP citrate lyase; a citrate lyase; an acetyl-CoA synthetase; an oxaloacetate transporter; a cytosolic palate dehydrogenase; a malate transporter; a mitochondrial malate dehydrogenase; a pyruvate oxidase (acetate forming); an acetyl-CoA ligase or transferase; an acetate kinase: a phosphotransacetylase; a pyTuvate decarboxylase; an acetaldehyde dehydrogenase; a pyruvate oxidase (acetyl-phosphate forming); a pyruvate dehydrogenase, a pyruvate:ferredoxin oxidoreductase or pyruvate formate iyase; a acetaldehyde dehydrogenase (acylating); a threonine aldolase; a mitochondrial acetylcarnitine transferase; a peroxisomal acetylcarnitine transferase; a cytosolic acetylcarnitine transferase; a mitochondrial acetyicarnitine translocase; a peroxisomal acetylcarnitine translocase; a PEP carboxylase; a PEP carboxykinase; an oxaloacetate decarboxylase; a malonate semialdehyde dehydrogenase (acetylating); an acetyl-CoA carboxylase; a malonyl-CoA decarboxylase; an oxaloacetate dehydrogenase; an oxaloacetate oxidoreductase; a malonyl-CoA reductase; a pyruvate carboxylase; a malonate semialdehyde dehydrogenase; a malonyl-CoA synthetase; a malonyl-CoA transferase; a malic enzyme; a palate dehydrogenase; a palate oxidoreductase; a pyruvate kinase; and a PEP phosphatase; and/or (2) the 1,3-BDO pathway comprises one or more enzymes selected from the group consisting of an acetoacetyl-CoA thiolase; an acetyl-CoA carboxylase; an acetoacetyl-CoA synthase; an acetoacetyl-CoA reductase (CoA-dependent, alcohol forming); 3-oxobutyraldehyde reductase (aldehyde reducing); 4-hydroxy,2-butanone reductase; an acetoacetyl-CoA reductase -39- (CoA-dependent, aldehyde forming); a 3-oxobutyraldehyde reductase (ketone reducing); 3 hydroxvbutyraldehyde reductase; an acetoacetyl-CoA reductase (ketone reducing); a 3 hydroxybutyryl-CoA reductase (aldehyde forming); a 3-hydroxybutyryl-CoA reductase (alcohol fonning); an acetoacetvi-CoA transferase, an acetoacetyl-CoA hydrolase, an acetoacetyl-CoA synthetase, or a phosphotransacetoacetylase and acetoacetate kinase; an acetoacetate reductase; a 3-hydroxybutyryl-CoA transferase, hydrolase, or synthetase; a 3-hydroxybutyrate reductase; and a 3-hvdroxybutyrate dehydrogenase. [00931 Any non-naturally occurring eukaryotic organism comprising an acetyl-CoA pathway and engineered to comprise an acetyl-CoA pathway enzyme, such as those provided herein, can be engineered to further comprise one or more 1,3-BDO pathway enzymes, such as those provided herein. 100941 Also provided herein is a method for producing 1,3-BDO, comprising culturing any one of the organisms provided herein comprising a I ,3-13DO pathway under conditions and for a sufficient period of time to produce 1,3-BDO. Dehydration of 1,3-BDO produced by the organisms and methods described herein, provides an opportunity to produce renewable butadiene in small end-use facilities, obviating the need to transport this flammable and reactive chemical. [00951 In a sixth aspect, provided herein is a method for producing I 3-BDO, comprising culturing a non-naturally occurring eukaryotic organism under conditions and for a sufficient period of time to produce the 1,3-BDO, wherein the non-naturally occurring eukaryotic organism comprises (1) an acetyl-CoA pathway; and (2) a 1,3-BDO pathway. In certain enibodiments, provided herein is a method for producing 1 3-BDO, comprising culturing a non-naturally occurring eukaryotic organism, comprising (1) an acetyl-CoA pathway, wherein said organism comprises at least one exogenous nucleic acid encoding an acetyl-CoA pathway enzyme expressed in a sufficient amount to (i) transport acetyl-CoA from a mitochondrion and/or peroxisonie of said organism to the cvtosol of said organism, (ii) produce acetyl-CoA in the cytoplasm of said organism, and/or (iii) increase acetyl-CoA in the cytosol of said organism; and (2) a 1,3-BDO pathway, wherein said organism comprises at least one exogenous nucleic acid encoding a 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO. In -40certain embodiments, (1) the acetyl-CoA pathway comprises one or more enzymes selected from the group consisting of a citrate synthase; a citrate transporter; a citrate/oxaloacetate transporter; a citrate/malate transporter; an ATPI citrate lyase; a citrate lyase; an acetyl-CoA synthetase; an oxaloacetate transporter; a cytosolic malate dehydrogenase; a palate transporter; a mitochondrial palate dehydrogenase; a pyruvate oxidase (acetate forming); an acetyl-CoA ligase or transferase; an acetate kinase; a phosphotransacetylase; a pyruivate decarboxyiase; an acetaldehyde dehydrogenase; a pyrivate oxidase (acetyl-phosphate forming); a pyruvate dehydrogenase, a pyruvate:ferredoxin oxidoreductase or pyruvate fonnate lyase; a acetaldehyde dehydrogenase (acylating); a threonine aldolase; a mitochondrial acetylcarnitine transferase; a peroxisomal acetyleamitine transferase; a cytosolic acetylcamitine transferase; a mitochondrial acetylearnitine translocase; a peroxisomal acetylcarnitine translocase; a PEP carboxylase; a PEP carboxykinase; an oxaloacetate decarboxylase; a malonate semialdehyde dehydrogenase (acetylating); an acetyl CoA carboxylase; a malonyl-CoA decarboxylase; an oxaloacetate dehydrogenase; an oxaloacetate oxidoreductase; a malonyl-CoA reductase; a pyruvate carboxylase; a malonate senialdehyde dehydrogenase; a malonyl-CoA synthetase; a malonyl-CoA transferase; a malic enzyme; a palate dehydrogenase; a palate oxidoreductase; a pyruvate kinase; and a PEP phosphatase; and (2) the 1,3-BDO pathway comprises one or more enzymes selected from the group consisting of an acetoacetyl-CoA thiolase; an acetyl-CoA carboxylase; an acetoacetyl CoA synthase; an acetoacetyl-CoA reductase (CoA-dependent, alcohol forming); 3 oxobutyraldehyde reductase aldehydee reducing); 4-hydroxy,2-butanone reductase; an acetoacetyl-CoA reductase (CoA-dependent, aldehyde fonning); a 3-oxobutyraldehyde reductase (ketone reducing); 3-hydroxybityraldehyde reductase; an acetoacetyl-CoA reductase (ketone reducing); a 3-hydroxybutyiyl-CoA reductase (aldehyde fonning); a 3-hydroxybutyryl-CoA reductase (alcohol forming); an acetoacetyl-CoA transferase, an acetoacetyl-CoA hydrolase, an acetoacetyl-CoA synthetase, or a phosphotransacetoacetylase and acetoacetate kinase; an acetoacetate reductase; a 3-hydroxybutyryl-CoA transferase, hydrolase, or synthetase; and a 3 hydroxybutyrate reductase; and a 3-hydroxybutyrate dehydrogenase. [0096] Any non-naturally occurring eukaryotic organism comprising an acetyl-CoA pathway and engineered to comprise an acetyl-CoA pathway enzyme, such as those provided herein, can be engineered to further comprise one or more 1,31-BDO pathway enznes. In some -41embodiments, successful engineering of an acetyl CoA pathway in combination with a 1.3-BDO pathway entails identifying an appropriate set of enzymes with sufficient activity and specificity, cloning their corresponding genes into a production host, optimizing culture conditions for the production of cytosolic acetyl-CoA and the production of 1,3-BDO, and assaying for the production or increase in levels of I ,3-BDO product formation. 100971 The conversion of acetyl-CoA to 1,3-BDO , for example, can be accomplished by a number of pathways in about three to six enzymatic steps as shown in FIG. 4. FIG. 4 outlines multiple routes for producing I,3-BDO from acetyl-CoA. Each of these pathways from acetyl CoA to 1,3-EDO utilizes three reducing equivalents and provides a theoretical yield of 1 mole of 1,3-BDO per mole of glucose consumed. Other carbon substrates such as syngas can also be used for the production of acetoacetyl-CoA. Gasification of glucose to form syngas will result in the maximum theoretical yield of 1.09 moles of 1,3-BDO per mole of glucose consumed, assuming that 6 moles of CO and 6 moles of H2 are obtained from glucose 6CO + 6H-> 1.091 C4HmO 2 + 1.636 C0 2 -i 0.545 H2 [00981 The methods provided herein are directed, in part, to methods for producing 1,3-BDO through culturing of these non-naturally occurring eukaryotic organisms. Dehydration of 1,3 BDO produced by the organisms and methods described herein, provides an opportunity to produce renewable butadiene in small end-use facilities obviating the need to transport this flammable and reactive chemical. [00991 In some embodiments, the non-naturally occurring eukaryotic organism comprises an acetyl-CoA pathway, wherein said organism comprises at least one exogenous nucleic acid encoding at least one acetyl-CoA pathway enzyme expressed in a sufficient amount to (i) transport acetyl-CoA from a mitochondrion and/or peroxisome of said organism to the cytosol of said organism, (ii) produce acetyl-CoA in the cytoplasm of said organism, and/or (iii) increase acetyl-CoA in the cytosol of said organism. In one embodiment, the at least one acetyl-CoA pathway enzyme expressed in a sufficient amount to transport acetyl-CoA from a mitochondrion and/or peroxisome of said organism to the cytosol of the organism. In one embodiment, the at least one acetyl-CoA pathway enzyme expressed in a sufficient amount to produce cytosolic -42acetyl CoA in said organism. In another embodiment, the at least one acetyl-CoA pathway enzyme is expressed in a sufficient amount to increase acetyl-CoA in the cytosol of said organism. [001001 In certain embodiments, the acetyl-CoA pathway comprises: 2A, 2B, 2C, 2D, 2E, 2F, 2G, 2K, 2L, 31-1, 31 or 3J, or any combination of 2A, 2B, 2C, 2D, 2E, 2F, 2G, 2K, 2L, 31], 31 and 3J, thereof; wherein 2A is a citrate synthase; 213 is a citrate transporter; 2C is a citrate/oxaloacetate transporter or a citrate/malate transporter; 2D is an ATP citrate lvase; 2E is a citrate lyase; 2F is an acetyl-CoA synthetase; 2G is an oxaloacetate transporter; 2K is an acetate kinase; 2L is a phosphotransacetylase; 3H is a cytosolic malate dehydrogenase; 31 is a malate transporter; and 3J is a mitochondrial palate dehydrogenase. In some embodiments, 2C is a citrate/oxaloacetate transporter. In other embodiments, 2C is a citrate/malate transporter. 1001011 In some embodiments, the acetyl-CoA pathway is an acetyl-CoA pathway depicted in FIG. 2. In other embodiments, the acetyl-CoA pathway is an acetyl-CoA pathway depicted in FIG. 3. In one embodiment, the acetyl-CoA pathway comprises 2A, 213 and 2D. In another embodiment, the acetv-CoA pathway comprises 2A, 2C and 2D. In yet another embodiment, the acetyl-CoA pathway comprises 2A, 2 1 B, 2C and 2D. In an embodiment, the acetyl-CoA pathway comprises 2A, 2B, 2E and 2F. In another embodiment, the acetyl-CoA pathway comprises 2A, 2C, 2E and 2F. In other embodiments, the acetyl-CoA pathway comprises 2A, 2B 2C, 2E and 2F. In some embodiments, the acetyl CoA pathway comprises 2A, 2B, 2E, 2K and 2L In another embodiment, the acetyl CoA pathway comprises 2A, 2C, 2E, 2K and 2L In other embodiments, the acetyl CoA pathway comprises 2A, 2B, 2C, 2E, 2K and 2L. In some embodiments, the acetyl-CoA pathway further comprises 2G, 3H, 31, 3J, or any combination thereof In certain embodiments, the acetyl-CoA pathway further comprises 2G. In some embodiments, the acetyl-CoA pathway further comprises 3H. In other embodiments, the acetyl CoA pathway further comprises 31. In vet other embodiments, the acetyl-CoA pathway further comprises 3J. In some embodiments, the acetyl-CoA pathway further comprises 2G and 3H. In an embodiment, the acetyl-CoA pathway further comprises 2(G and 31. In one embodiment, the acetyl-CoA pathway further comprises 2G and 3J. In some embodiments, the acetyl-CoA pathway further comprises 31 and 31. In other embodiments, the acetyl-CoA pathway further -43comprises 3H and 3J. In certain embodiments, the acetyl-CoA pathway further comprises 31 and 3J. In another embodiment, the acetyl-CoA pathway further comprises 2G, 3H and 31. In yet another embodiment, the acetyl-CoA pathway further comprises 2G, 31H and 3J. In some embodiments, the acetyl-CoA pathway further comprises 2G, 31 and 3J. In other embodiments, the acetyl-CoA pathway further comprises 3H, 31 and 3J. 1001021 In one embodiment, the acetyl-CoA pathway comprises 2A. In another embodiment, the acetyl-CoA pathway comprises 2B. In an embodiment, the acetyl-CoA pathway comprises 2C. In another embodiment, the acetyl-CoA pathway comprises 21). In one embodiment, the acetyl-CoA pathway comprises 2E. In yet another embodiment, the acetyl-CoA pathway comprises 2F. In some embodiments, the acetyl-CoA pathway comprises 2G. In some embodiments, the acetyl-CoA pathway comprises 2K. In another embodiment, the acetyl-coA pathway comprises 2L. In other embodiments, the acetyl-CoA pathway comprises 3H, In another embodiment, the acetyl-CoA pathway comprises 31. In one embodiment, the acetyl-CoA pathway comprises 3J. [001031 In some embodiments, the acetyl-CoA pathway comprises: 2A and 213; 2A and 2C; 2A and 21); 2A and 2E; 2A and 2F; 2A and 20 2A and 2K; 2A and 2L; 2A and 3kH; 2A and 31; 2A and 3J; 2B and 2C; 2B and 2D; 2B and 2E; 2B and 2F; 2B and 2G 213 and 2K; 2B and 2L; 213 and 31-1; 2B and 31; 2B and 3.1; 2C and 21); 2C and 2E; 2C and 2F; 2C and 2G; 2C and 2K; 2C and 2L; 2C and 3H; 2C and 31; 2C and 3J; 2D and 2E; 2D and 2F; 2D and 2G; 2D and 2E; 2D and 2F; 2D and 2G; 2D and 2K; 2D and 2L; 2D and 3k; 2D and 31; 2D and 3d: 2E and 2F; 2E and 2G; 2E and 2K; 2E and 2L; 2E and 3H: 2E and 31; 2E and 3d; 2F and 2G; 2F and 2K; 2F and 2L; 2F and 3; 2F and 31; 2F and 3J; 2G and 2K; 2G and 21; 2G and 311; 2G and 31; 2G and 3J; 2K and 2L; 2K and 3H; 2K and 31; 2K and 3J; 2L and 3H; 2L and 31; 2L and 3J; 3H and 31; 3H and 3J; or 31 and 3J. In some embodiments, the non-naturally occurring eukaryotic organism comprises two or more exogenous nucleic acids, wherein each of the two or more exogenous nucleic acids encodes a different acetyl-CoA pathway enzyme. [001041 In other embodiments, the acetyl-CoA pathway comprises: 2A, 2B and 2C; 2A, 2B and 2D; 2A, 2B and 2E; 2A, 2B and 2F; 2A, 2B and 2G; 2A, 213 and 21K; 2A, 2B and 2L; 2A, 2B and 3H; 2A, 2B and 31; 2A, 213 and 3d; 2A, 2C and 2D; 2A, 2C and 2E; 2A, 2C and 2F; 2A, 2C -44and 2G; 2A, 2C and 2K; 2A, 2C and 2L; 2A, 2C and 3H; 2A, 2C and 31 2A, 2C and 3J; 2A, 2D and 2E; 2A, 21) and 2F; 2A, 2D and 2G; 2A, 2D and 2K; 2A, 2D and 2L; 2A, 21) and 3; 2A, 2D and 31; 2A, 2D and 3]; 2A, 2E and 2F; 2A, 2E and 2G; 2A, 2E and 2K; 2A, 2E and 2L; 2A, 2E and 3; 2A, 2E and 31; 2A, 2E and 3J; 2A, 2F and 2G; 2A, 2F and 2K; 2A 2F and 2L; 2A, 2F and 3H; 2A,2F and 31; 2A. 2F and 3J; 2B, 2C and 2D; 213, 2C and 2E; 2B, 2C and 2F; 2B, 2C and 2G; 2B, 2C and 2K; 2B, 2T and 2L; 213 2T and 311; 213, 2C and 31; 2B, 2C and 3J; 2B, 2D and 2E; 213, 21) and 2F; 213, 2D and 2G; 2B, 2D and 2K 2B,2) and 2L; 213, 2D and 3[I; 213, 2D and 31; 2B, 2D and 3J; 2B. 2E and 2; 2B, 2E and 2G; 2B, 2E and 2K; 213, 2E and 2L; 2B. 2E and.3F 3H 21 and 31; 2B, 2E and 3J; 213, 21 and 2G; 213,2F and 2K; 23, 2F and 2L; 2B, 21F and 3H; 2B, 2F and 31; 2B, 21 and 3J; 213, 2G and 2K; 21B, 2G and 2L; 2B, 2G and 3H; 2B. 2G and 31; 23, 2G and 3J; 213, 2K and 21 2B, 2K and 3H; 2B, 21K and 31;2B, 2K and 31; 2B, 2L and 3H3; 2B, 2L and 31; 213, 2L and 3J; 2C, 2D and 2E; 2C, 2D and 213; 2C. 2D and 2G; 2C, 2D and 2K; 2C, 2D and 2L; 2C, 2D and 31-1; 2C, 2D and 31; 2C, 2D and 33; 2C, 2E and 2F; 2C, 2E and 2G; 2C, 2E and 2K; 2C, 2E and 2L; 2C, 21E and 3H; 2C, 2E and 31; 2C, 2E and 3J; 2C, 2F and 2G; 2C, 2F and 2K; 2C, 2F and 21; 2C, 2F and 2G; 2C, 2F and 2K; 2C, 2F and 2L; 2C, 2F and 3; 2C, 2F and 31; 2(, 2F and 3J; 2D, 2E and 2F; 2D), 2E and 2G; 21), 2E and 2K 2D, 2E and 2L; 2D, 2E and 3H; 2D, 2E and 31; 2D. 2E and 3J; 2D, 2F and 2G; 2D, 21 and 2K; 2D, 2F and 2L; 21), 21 and 31-1; 21), 2F and 31;)2D, 2F and 3J; 21D, 2G and 2K; 2D, 2G and 21L; 21), 2G and 3H; 2D, 2G and 31; 2D. 2G and 3J; 2D, 2K and 2L; 2D, 2K and 3H; 2D, 2K and 31; 2D, 2K and 3J; 2D, 2L and 31; 2D, 2L and 31 2D 2 1 and 3J; 2D, 311 and 31; 2D, 311 and 3J; 2D, 31 and 3J; 2E, 2 and 2; 2E, 2F and 2K; 2E, 2F and 2L; 2E, 2F and 31H; 2E, 2F and 31; 2E, 2F and 3J; 2E,2G and 2K; 213.2G and 21; 2E, 2G and 311; 2E, 2G and 31; 2E,1 G and 33; 2K, 2L and 311; 2K, 2L and 31; 2K, 2L and 31; 2K, 3H and 31; 2K, 3H and 3J; 2K, 31 and 3J; 2L, 3H and 31; 2L, 3H and 3J; 2L, 31 and 3J; or 3H, 31 and 3J. In some embodiments. the non-naturally occurring eukaryotic organism comprises three or more exogenous nucleic acids, wherein each of the three or more exogenous nucleic acids encodes a different acetyl-CoA pathway enzyme. [00105] In certain embodiments, the acetyl CoA pathway comprises: 2A, 213, 2(C and 2D; 2A, 2B, 2C and 2E; 2A, 2B, 2C and 2F; 2A, 2B, 2C and 2G; 2A, 2B, 2C and 2K; 2A, 213, 2C and 2L; 2A, 2B 2(C and 3H; 2A, 2B, 2C and 31; 2A, 2B, 2C and 3J; 2A, 2B, 2D and 2E; 2A, 213, D and 2F; 2A, 2B, 2D and 2G; 2A, 2B, 2D and 2K.; 2A, 2B, 2D and 2L; 2A, 2B, 2D and 311; 2A, 2B, -45- 2D and 31; 2A, 2B, 2D and 3J; 2A, 2B, 2E and 2F; 2A, 2B, 2E and 2G; 2A, 2B, 2E and 2K; 2A, 2B, 2E and 2L; 2A, 2B, 2E and 3H; 2A, 2B, 2E and 31 2A, 2B, 2E and 3J; 2A, 2B, 2F and 20; 2A, 2B, 2F and 2H; 2A, 2B, 2F and 21; 2A, 2B, 2F and 3H; 2A, 2B, 2F and 31; 2A, 2B, 2F and 31; 2A, 2B, 2G and 2K; 2A, 2B, 2G and 2L; 2A, 2B, 2G and 3fH; 2A, 2B, 2G and 31; 2A, 2B, 2G and 3J; 2A, 2B, 2K and 2L; 2A, 2B, 2K and 3 H; 2A, 2B, 2K and 31; 2A, 2B, 2K and 3J; 2A, 2B, 2L and 3H; 2A, 2B, 2L and 31; 2A, 2B, 2L and 3J; 2A, 2B, 31 and 31; 2A 2B, 3 and 3J; 2A, 2B, 31 and 3J; 2A, 2C, 2) and 2E; 2A, 2C, 2D and 2F; 2A, 2C, 2) and 2G; 2A, 2C, 2) and 2K; 2A, 2C, 2D and 2L; 2A, 2C, 2D and 3H; 2A, 2C, 2D and 31; 2A, 2C, 2D and 31 2A, 2C, 2E and 2F; 2A, 2C, 2E and 2G; 2A, 2C, 2E and 2K; 2A, 2C, 2E and 2L; 2A, 2C, 2E and 3H; 2A, 2C, 2E and 31; 2A, 2C, 2E and 3J; 2A, 2C, 2F and 2G; 2A, 2C, 2F and 2K; 2A, 2C, 2F and 2L; 2A, 2C, 2F and 3H; 2A, 2C, 2F and 31; 2A, 2C, 2F and 3J; 2A, 2C, 2G and 2K; 2A, 2C, 2G and 2L; 2A, 2C, 2G and 3H; 2A, 2C, 2G and 31; 2A, 2C, 2G and 33; 2A, 2C, 2K and 2L; 2A, 2C, 2K and 3H; 2A, 2C, 2K and 31; 2A, 2C, 2K and 3J 2A, 2C, 2L and 31; 2A, 2C, 2L and 31; 2A, 2C, 2L and 3J; 2A, 2C, 3H and 31: 2A, 2C, 3H and 3J; 2A, 2C, 31 and 3J; 2A, 2D, 2E and 2F; 2A 2D, 2E and 2G; 2A, 2D, 2E and 2K; 2A, 2D, 2E and 2L; 2A, 2D, 2E and 3H; 2A, 2D, 2E and 3; 2A, 2D, 2E and 3J; 2A, 2D, 2F and 2G; 2A, 2D, 2F and 2K; 2A, 2D, 2F and 2L; 2A, 2D, 2F and 3fH; 2A, 2D, 2F and 31: 2A, 2D, 2F and 3J; 2A, 2D, 2G and 2K; 2A, 2D, 2G and 2L; 2A, 2D, 2G and 3H; 2A, 2D, 2G and 31; 2A, 2D, 2G and 3.1; 2A, 2D, 2K and 2L; 2A, 2D, 2K and 3H; 2A, 2D, 2K and 31; 2A, 2D, 2K and 3J; 2A, 2D, 2L and 3H; 2A, 2D, 2L and 31; 2A, 2D, 2L and 3J; 2A, 2D, 3H and 31; 2A, 2D, 311 and 3J; 2A, 2D, 31 and 3J; 2A, 2E, 2F and 2G; 2A, 2E, 2F and 2K; 2A, 2E, 2F and 2L; 2A, 2E, 2F and 3kH; 2A, 2E, 2F and 31; 2A, 2E, 2F and 3J; 2A, 2E, 2G and 2K; 2A, 2E, 2G and 2L; 2A, 2E, 2G and 311; 2A, 2E, 2G and 31; 2A, 2E, 2G and 33; 2A, 2E, 2K and 2L; 2A, 2E, 2K and 3H; 2A, 2E, 2K and 31; 2A, 2E, 2K and 3J; 2A, 2E, 2L and 3H; 2A, 2E, 2L and 3; 2A, 2E, 2L and 3J; 2A, 2E, 3H and 31; 2A, 2E, 3H and 3J 2A, 2E, 31 and 3J; 2A, 2F, 2G and 2K; 2A, 2F, 2G and 2L; 2A, 2F, 2G and 3H; 2A, 2F, 2G and 31; 2A, 21F, 2G and 33; 2A, 2F, 2K and 2L; 2A, 2F, 2K and 3H; 2A, 2F 2K and 31; 2A, 2F, 2K and 3J; 2A, 2F, 2L and 3H; 2A, 2F, 2L and 31 2A, "F 2L and 3J; 2A, 2F, 3H and 31; 2A, 2F, 311 and 3J; 2A, 21., 31 and 31; 2A, 2G, 2K and 2L; 2A, 2G, 2K and 3H; 2A, 2G, 2K and 31; 2A, 2G, 2K and 3J; 2A, 2G, 2L and 31; 2A, 2G, 2L and 31; 2A, 2G, 2L and 3J; 2A, 2G, 311 and 31; 2A, 2G, 311 and 33; 2A, 2G, 31 and 3J; 2A, 3k, 31 and 3J; 2B, 2C, 2D and 2E; 2B, 2C, 2D and 2F; 2B, 2C, 2D and 20; 2B, 2C, -46- 2D and 2K; 2B, 2C, 2D and 2L; 2B, 2C, 2D and 3H; 2B, 2C, 2D and 31; 2B, 2C, 2D and 3J; 2B, 2C, 2E and 2F; 2B, 2C, 2E and 2G; 213, 2, 2E and 2K; 2B, 2C, 2E and 2L; 2B, 2C, 2E and 3 H; 2B, 2C, 2E and 31; 2B, 2C, 2E and 3J; 2B, 2C, 2F and 2G; 2B, 2C, 2F and 2K; 2B, 2C, 2F and 2L; 2B, 2C, 2F and 3H; 2B, 2C, 2F and 31; 2B, 2C, 2F and 3d; 2B, 2C, 2G and 2K; 2B, 2C, 2G and 2L; 2B, 2C, 2G and 3H; 2B, 2C, 2G and 31; 2B, 2C, 2G and 3J; 2B, 2C, 2K and 2L; 2B, 2C, 2K and 3H; 2B 2C, 2K and 31; 2B, 2C, 2K and 3J; 2B, 2C, 2L and 3H; 2B, 2C, 2L and 31; 2B, 2C, 2L and 33; 2B, 2C, 3H and 31; 2B, 2C, 31H and 3J; 213, 2C, 31 and 3J; 213, 2D, 2E. and 21F; 213, 2D, 2E and 2G; 2B, 2D, 2E and 2K; 2B, 2D, 2E and 2L; 2B, 2D, 2E and 3H; 2B, 2D, 2E and 31; 2B, 2D, 2E and 31; 2B, 21)B , 21 and 2G; 2B, 2D, 2F and 2K; 2B, 2D, 2F and 2L; 2B, 2D, 2F and 3H; 2B, 2D, 2F and 31; 2B, 2D, 2F and 3d; 2B, 2D, 2G and 2K; 2B, 2D, 2G and 2L; 2B, 2D, 2G and 3H; 2B 2D, 2G and 31; 2B, 2D, 2G and 3d; 2B, 2D, 2K and 2L; 2B, 2D, 2K and 3H; 2B, 2D, 2K and 31; 2B, 2D, 2K and 3d; 2B, 2D, 2L and 3H; 2B, 2D, 2L and 31; 2B, 2D, 2L and 3J; 2B, 2D, 311 and 31; 2B, 2D, 31] and 3d; 2B, 2D, 31 and 3J; 2B, 2E, 2F and 2G; 2B, 2E, 2F and 2K; 2B, 2E, 2F and 2L; 2B, 2E, 2F and 3H; 2B, 2E, 2F and 31; 2B, 2E, 2F and 3J; 2B, 2E, 2G and 2K; 2B, 2E, 2G and 2L; 2B, 2E, 2G and 3H; 2B, 2E, 2G and 31; 2B, 2E, 2G and 3J; 2B, 2E, 2K and 2L; 213, 213, 21K and 3H; 213, 2E, 2K and 31; 213, 21E, 21K and 3J; 213, 21E, 2L and 31 -; 213, 21, 2L and 31; 2B, 2E, 2L and 3d; 2B, 2E 3H and 31; 2B, 2E, 3H and 3J; 2B, 2E, 31 and 3J; 2B, 2F, 2G and 2K; 2B, 2F, 2G and 2L; 2B, 2F, 2G and 31H; 2B, 2F, 2G and 31; 213, 2F, 2G and 31; 2B, 2F, 2K and 2L; 2B, 2F, 2K and 31; 2B, 2F, 2K and 31; 2B, 2F, 2K and 3J; 2B, 2F, 2L and 3H; 2B, 2F, 2L and 31; 2B, 2F, 2L and 3J; 2B, 2F, 311 and 31; 2B, 2F, 311 and 3J; 2B, 2F, 31 and 3J; 2B, 2G, 2K and 2L; 2B, 2G, 2K and 3H; 2B, 2G, 2K and 31; 2B, 2G, 2K and 33; 2B, 2G, 2L and 3Hi; 2B, 2G, 2L and 31; 2B, 2G, 2L and 3d; 2B, 2G, 3Hi and 31; 2B, 2G, 311 and 3J; 2B, 311, 31 and 3d; 2B, 2K, 2L and 3H; 2B, 2K, 2L and 31; 2B, 2K, 2L and 3d; 2B, 2K, 31H and 31; 2B, 2K, 3H and 3J; 2B, 2K, 31 and 31 2B, 2L, 3H and 31; 2B, 2L, 3H and 3J; 2B, 2L, 31 and 3J; 2B, 3H, 31 and 3d; 2C, 2D, 2E and 2F; 2C, 2D, 2E and 2G; 2C, 2D, 2E and 2K; 2C, 2D, 2E and 2L; 2C, 2D, 2E and 31; 2C, 2D, 2E and 31; 2C 2D, 2E and 3d; 2C, 2D, 2F and 20; 2C, 2D, 2F and 2K; 2C, 2D, 2F and 2L; 2C, 2D, 2F and 31; 2C, 2D, 2F and 31; 2C, 2D, 2F and 3d; 2C, 2D, 2G and 2K; 2C, 2D, 2G and 2L; 2C, 2D, 2G and 3H; 2C, 2D, 2G and 31; 2C, 2D, 2G and 3J; 2C, 2D, 3H and 31; 2C, 2D, 2K and 2L; 2C 2D, 2K and 3; 2C, 2D, 2K and 31; 2C, 2D, 2K and 33; 2C, 2D, 2L and 3H; 2C, 2D, 2L and 31: 2C, 2D, 2L and 3d; 2C 2D, 3H and 31; 2C, 2D, 3H and 3J; 2C, -47- 2D, 31 and 3J; 2C, 2E, 2F and 2G; 2C, 2E, 2F and 2K; 2C, 2E, 2F and 2L; 2C, 2E, 2F and 3H; 2C, 2E, 2F and 3; 2C, 2E, 2F and 3J; 2C, 2E3, 2G and 2K; 2C, 2E, 2E2 and 21; 2(, 2, 2G and 3H; 2C, 2E, 2G and 31; 2C, 2E, 2G and 3J; 2C, 2E, 2K and 2L; 2C, 2E, 2K and 3H; 2C, 2E, 2K and 31; 2C, 2E, 2K and 3J; 2C, 2E, 2L and 3H; 2C, 2E, 21L and 31; 2C, 2E, 2L and 3J; 2C, 2E, 31 and 31; 2C, 2E, 3H and 3J; 2C, 2E, 31 and 3; 2C, 2f, 2G and 2K; 2C, 2F, 2G and 2L; 2C, 2F, 2G and 3H; 2C, 2F, 2G and 31; 2C, 2F, 2G and 3J; 2C, 2F, 2K and 2L; 2C, 2F, 2K and 31H; 2C, 2F, 2K and 31 2C, 2F, 2K and 31 2(C 2F, 2L and 3H; 2C, 2F, 21L and 3I; 2C, 2F, 2L and 3J; 2C, 2F, 3H and 31; 2C, 2F, 311 and 3J; 2C, 2F, 31 and 3J; 2C, 2G, 2K and 2L; 2C, 2G, 2K and 3H; 2C, 2G, 2K and 31; 2C, 2G, 2K and 3; 2C, 26, 2L and 3H; 2C, 2G, 2L and 3; 2Q 26, 2L and 33; 2C, 2G, 3H and 31; 2C, 2G, 3H and 3J; 2C, 2G, 31 and 3J; 2C, 2K, 2L and 3H; 2C, 2K, 2L and 31; 2C, 2K, 2L and 3; 2C, 2K, 3H and 31; 2C, 2K, 3H and 3J; 2C, 2K, 31 and 33; 2C, 2L, 31H and 31; 2C, 2L, 3H and 3J; 2C, 2L, 31 and 33; 2C, 3H, 31 and 3J; 2D, 2E, 2F and 2G; 2D, 2E, 2F and 2K; 2D 2E, 2F and 2L; 2D, 2E, 2F and 3H; 2D, 2E, 2F and 31; 2D, 2E, 2F and 33; 2D, 2E, 2G and 2K; 2D, 2E, 2G and 2L; 2D, 2E, 2G and 3H; 2D, 2E. 2G and 31; 2D, 2E, 2G and 3J; 2D, 2E, 2K and 2L; 2D, 2E, 2K and 3H; 2D. 2E. 2K and 31' 2D 2E, 2K and 3J; 2D, 2E, 2L and 31; 2D, 2E. 2L and 31: 2D, 2E, 213 and 2 1 D, 2E, 3H and 31; 21, 2E, 3 and 3J; 2D, 2E, 31 and 3J; 2D, 2F, 2G and 2K; 2D, 2F, 2G and 2L; 2D, 2F, 2G and 3H; 2D, 2F, 2G and 31; 2D, 2F, 2G and 3J; 2D, 2F, 2K and 2L; 2D, 2F, 2K and 31H; 213, 213, 2K and 31; 2D, 21, 2K and 3J; 213, 21F, 2L and 3H; 2D, 2f, 2L and 31; 2D, 2F, 21. and 3J; 2D, 2F, 3H and 31; 2D, 2F, 3H and 3J; 2D, 2F, 31 and 3J; 2E, 2F, 2G and 3H1; 2E, 2F, 2G and 31; 2E, 2F, 2G and 3J; 2E, 2F, 31] and 31; 2E, 2F, 31] and 3; 2E, 2F, 31 and 3J; 2F, 2G, 3H and 31; 2F, 2G, 3H and 3J; 2F, 2G, 31 and 3J; or 2G, 3H, 31 and 33, 2D, 2G, 2K and 2L; 2D, 2G, 2K and 31; 2D, 2G, 2K and 31; 2D, 2G, 2K and 3J; 2D, 2G, 2L and 3H; 2D, 2G, 2L and 31; 2D, 2G, 2L and 3J; 2D, 2G, 2H and 31; 2D, 2G, 2H and 3J; 2D, 2G, 31 and 3J; 2D, 2K, 2L and 3H; 2D, 2K, 2L and 31; 2D, 2K, 2L and 3J; 2D, 2K, 3H and 31; 2D, 2K, 311 and 33; 21), 2K, 31 and 3J; 21D, 21, 3H and 31; 2D, 21, 3Ff and 3J; 21), 3H, 31 and 3.; 2 1 D, 3H, 31 and 3J; 2E, 2F, 2G and 2K; 2E, 2F, 2G and 2L; 2E, 2F, 2G and 3H; 2E, 2F, 2G and 31; 2E, 2F, 2G and 3J; 2E, 2F, 2K and 2L; 2E, 2F, 2K and 31H; 2E, 2F, 2K and 31; 2E, 2F, 2K and 3J; 2E, 2F, 2L and 311; 2E, 2F, 21 and 31; 2E, 2F, 2L and 3J; 2E, 2F, 31H and 31; 2E, 2F, 3H and 3J; 2E, 2f, 31 and 3J; 2E, 2G, 2K and 2L; 2E, 2G, 2K and 31H; 2E, 2G, 2K and 31; 2E, 2G, 2K and 33; 2E, 2G, 2L and 3H; 2E, 2G, 2L and 31; 2E, 2G, 2L and 3J; 2E, 2G, 3H and 31; 2E, 2G, 3H -48and 3J; 2E, 2G, 31 and 3J; 2E, 2K, 2L and 3H; 2E 2K, 2L and 31; 2E, 2K, 2L and 3J; 2E, 2K, 3H and 31; 2E, 2K, 3H and 3J; 2E, 2K 31 and 3J; 2E, 2L, 31-I and 31; 2E, 2L, 3i and 3J; 2E, 2L, 31 and 3J; 2E, 3H, 3 and 3. 2F, 2G, 2K and 2L; 2F, 2G, 2K and 3H; 2F, 2G, 2K and 31; 2F, 2G, 21K and 3J; 2F, 2G 2L and 31; 2F, 2G, 2L and 31; 2F, 2G, 2L and 3J; 2F, 2G, 3H and 31; 2F, 2G, 3H and 3J; 2F, 2G, 31 and 3; 2F, 2K, 2L and 3H; 2F, 2K, 2L and 31; 2F, 2K, 2L and 3J; 2F, 2K, 311 and 31; 2F, 2K, 3H and 33; 2F, 2K, 31 and 3J; 2F, 31], 31 and 31 2G, 2K, 2L and 31H; 2G, 2K, 2L and 31; 2G, 2K, 2L and 3J; 2G, 2K, 3H and 31; 2G, 2K, 3H and 3J; 2G, 2K, 31 and 3J; 2G, 2L, 3H and 31; 2G, 2L, 311 and 3J; 2G, 2L, 31 and 3J; 2G, 3H, 31 and 3J; 2K, 2L, 3H and 31; 2K, 2L, 3H and 33; 2K, 2L, 31 and 33; or 2L, 31-1, 31 and 3J. In some embodiments, the non-naturally occurring eukaryotic organism comprises four or more exogenous nucleic acids, wherein each of the four or more exogenous nucleic acids encodes a different acetyl-CoA pathway enzyme. [00106] In other enibodinients, the acetyl CoA pathway comprises: 2A, 2B, 2C, 2D and 2E; 2A, 21, 2C, 2D and 2F; 2A, 2B, 2C, 2D and 2G; 2A, 2B, 2C, 2D and 3H; 2A, 21B, 2C, 2D and 31; 2A, 2B, 2C, 2D and 33; 2A, 2B, 2C, 2E and 2F; 2A, 213, 2C, 2E and 2G; 2A, 2B, 2C, 2E and 31; 2A, 2B, 2C, 2E and 31; 2A, 2B, 2C, 2E and 3J; 2A, 2B, 2C, 2F and 2G; 2A, 2B, 2C, 2F and 3H; 2A, 2B, 2C, 2F and 31; 2A, 2B, 2C, 2F and 3J; 2A, 2B, 2C, 2G and 3H; 2A, 2B, 2C, 2G and 31; 2A, 2B, 2C, 2G and 3J; 2A, 213, 2C, 31H and 31 2A, 2B, 2C, 31- and 3J; 2A, 2B, 2C, 31 and 3J; 2A, 2B, 2D, 2E and 3H; 2A, 2B, 2D, 2E and 31; 2A, 2B, 2D, 2E and 3J; 2A, 2B, 2D, 2F and 2G; 2A, 2B, 2D, 2F and 31H; 2A, 2B, 2D, 2F and 31; 2A, 2B, 2D, 2F and 3J; 2A, 2B, 2D, 2G and 31; 2A, 2B, 2D, 2G and 31; 2A, 2B, 2D, 2G and 3J; 2A, 2B, 2D, 31H and 31; 2A, 2B, 2D, 3H and 3J; 2A, 2B, 2D, 31 and 3J; 2A, 2B, 2E, 2F and 2G; 2A, 21 2E, 2F and 311; 2A, 21, 2E, 2F and 31; 2A, 2B 2E, 2F and 3J; 2A, 2B, 2E, 2G and 3H; 2A, 2B, 2E, 2G and 31; 2A, 21B, 2E, 2G and 33; 2A, 2B, 2E, 3H and 31; 2A, 2B, 2E, 31 and 3J; 2A, 213, 2E, 31 and 3J; 2A, 2B, 2F, 2G and 31; 2A, 213, 2F, 2G and 31 2 2B, 213, 2G and 33; 2A, 2B, 2F, 31- and 31; 2A, 213, 2F, 3 1-1 and 3J; 2A, 2B, 2F, 31 and 3J; 2A, 2B, 2G, 3H and 31 2A, 2B, 2G, 3H and 3J; 2A, 2B, 2G, 31 and 3J; 2A, 213, 31-1, 31 and 3J; 2A, 2C, 2D, 2E and 2F; 2A, 2C, 2D, 2E and 2G; 2A, 2C, 21D, 2E and 31-1; 2A, 2C, 2D, 2E and 31; 2A, 2C, 2D, 2E and 3J; 2A, 2C, 2D, 2F and 2G; 2A, 2C, 2D, 2F and 3H; 2A, 2C, 2D, 2F and 31; 2A, 2C, 2D, 2F and 33; 2A, 2C, 2D, 2G and 31; 2A, 2C, 2D, 2G and 31; 2A, 2C, 2D, 2G and 3J; 2A, 2C, 2D, 3H and 31; 2A, 2C, 2D, 31H and 3J; 2A, 2C, 2D, 31 and 3J; 2A, 2C, 2E, 2F and 2; 2A, 2C, 2E, 2F and 31; 2A, 2C, 2E, 2F and 31; 2A, 2C, 2E, 2F and 33; -49- 2A, 2C, 2E, 2G and 3H; 2A, 2C, 2E, 2G and 31; 2A, 2C, 2E, 2G and 3J; 2A, 2C, 2E, 3H and 31; 2A, 2C, 2E, 31- and 3; 2A, 2C, 2E, 31 and3; 2A, 2C, F 2G and 3H; 2A, 2C, 2F, 2G and.3I; 2A, 2CF, 2G and 3.; 2A, 2C, 2F, 3H and 3I; 2A, 2C, 2F, 3H and 3J; 2A , 2F, 3 and 31; 2A, 2C, 2G, 3H and 31; 2A, 2C, 2G, 3H and 3; 2A, 2C, 2G, 31 and 33; 2A, 2C, 3, 31 and 3J; 2A, 2D, 2E, 2F and 31; 2A 2C, 2E(, 2F and 3H; 2A, 2D, 2E, 2F and 3; 2A, 2, 2E, 2F and 3J; 2A, 2D, 2E, 2G and 30; 2A, 2D, 2E, 2G and 3I; 2A, 2D, 2E, 2G and 31; 2A, 2D, 2E, 3H and 31; 2A, 2D, 2E, 3H and 3; 2A, 2D, 2E, 31 and 3J; 2A, 2D, 2F, 2G and 3H; 2A, 2D, 2F, 2G and 3 1; 2A, 2D, 2F, 2G and 3J; 2A, 2D, 2F, 3H and 3I; 2A, 2D, 2F, 3H and 3J; 2A, 2D, 2F, 3I and 3J; 2A, 2D, 2G, 2H and 3J; 2A, 2D, 2G, 3H and 3J; 2A, 2D, 2G, 31 and 3J; 2A, 2D, 311, 31 and 3J; 2A, 2E, 2F, 2G and 3H; 2A, 2E, 2F, 2G and 3; 2A, 2E, 2F, 2G and 3J; 2A, 2E, 2F, 3H and 3J; 2A, 2E, 2F, 3H and 3J; 2A, 2E, 2F, 31 and 3; 2A, 2E, 2G, 3H and 3; 2A, 2E, 2G, 3H and 3J; 2A, 2E, 2G, 31 and 3J; 2A, 21, 2F, 31 and 3J; 2A, 2F, 2G, 3H and 31; 2A, 2F, 2G, 3H and 3J; 2A, 2F, 2G, 31 and 33: 2A, 2F, 3H,. 31 and 3J; 2A, 2F, 20, 31 and 3J; 2B, 2C, 2D, 2E and 2F; 2B, 2C, 2D, 2E and 2G; 2B, 2C, 2D, 2E and 3; 2B, 2C, 2D, 2E and 31; 2B, 2C 2D, 2E and 3J; 2B, 2C, 2D, 2F and 2G; 2B, 2C, 2D, 2F and 3H; 2B, 2C, 2D, 2F and 31; 2B, 2C, 2D, 2F and 3J; 2B, 2C, 2D, 2G and 3H; 2B, 2C, 2D, 2G and 31; 213, 2C, 2D, 2G and 31; 213, 2C, 2D, 2F and 3; 213, 2C, 2D, 3H and 3J; 2B, 2C, 2D, 2 and 31; 2B, 2C, 2E, 2F and 2G; 2B, 2C, 2E, 2F and 3; 2B, 2C, 2E, 2 and 3; 213, 2C, 2E, 2F and 31; 213, 2C, 2E, 2G and 3; 2B, 2C, 2E, 2G and 31; 2B, 2C, 2E, 2G and 3J; 2B, "C 2 , 2311 and 3; 2, 2C, 2E, 3H and 3J; 2B, 2C, 2E, 3I and 3J; 2B, 2C, 2F, 2G and 3H; 2B, 2C, 2F, 2G and 31; 2B, 2C, 2F, 2G and 3J; 2B, 2C, 2F, 3H and 31; 2B, 2C, 2F, 3H and 31; 2B 2C, 2F, 3I and 3J; 2B, 2C, 2G, 3H and 3J; 2B. 2C, 2G, 3H and 31; 2B, 2C, 2G, 31 and 3; 2B, 2C, 311, 31 and 3; 2B, 2D, 2E, 2F and 2G; 2B, 2D, 2E, 2F and 3H; 2B, 2D, 2E, 2F and 3J; 2, 2C, 12E, 2F and 3J; 2B, 2D, 2E, 2G and 3H; 2B, 2D 2E, 2G and 3I; 2B, 2D, 2E, 2G and 31; 2B, 2 , 23H and 3I; 2B, 2D, 2E, 3H and 3J; 2B, 2D, 2E, 3I and 3J; 2B, 2D, 211 2G and 3 H; 2B, 21 , 2G and 31; 2B, 2D, 2F, 3G and 3J; 2B, 2D, 2F, 31 and 31; 213, 2D, 2F, 3 and 3J 21B 2E, 2DF, 3I and 3J; 2B, 2E, 2F, 2G and 3H; 2B, 2E, 2F, 2G and 31; 2B, 2E, 2F, 2G and 3J; 2B, 2E, 2F, 31 and 3J; 2, 2E, 2F, 3H and 3H; 2B, 2E, 2F, 3I and 311 23E, 2G, 3 H and 3l; 2B, 2E, 2G, 3H and 3J; 2B, 2E, 2G, 31 and 3J; 2B, 2E, 3 H, 31 and 3J; 2B, 2F, 2G, 3H and 31; 2B, 2F, 2G, 3H and 3J; 21, 2F, 20, 31 and 3J; 2B, 2G, 311, 31 and 3J; 2C, 2D, 2E, 2F and 3H; 2C, 2D, 2E, 2F and 31; 2C, 2D, 2E, 2F and 3J; 2C, 2D, 2E, 2G and 3H; 2C, 2D, 2E, 2G -50and 31; 2C, 2D. 2E, 2G and 3J 2C, 2D., 2E, 3H and 31; 2C, 2D, 2E, 3H and 3J; 2C, 2D, 2E, 31 and 31; 2C, 21), 2F, 2G and 3[1; 2C, 21, 21, 2G and 31; 2C, 2), 2F, 2G and 3J; 2C, 21D, 21F, 3H and 31; 2C, 2D, 2F, 3H and 3J; 2C, 21D, 2F, 3I and 3J; 2C, 2D, 2G, 3H and 31; AC, 2D, 2G, 3H and 3J; 2C, 2D, 2G, 31 and 3J 2C, D, 311, 31 and 33; 2D, 2E, 2F, 2G and 3H; 2D, 2E, 2F, 2G and 31; 2D, 2E, 2F, 2G and 3J; 2D, 2E, 2F, 3H and 31; 2D, 2E, 2F, 3H and 3J; 2D, 2E, 2F, 31 and 3J; 2D, 21E, 2G, 3 and 31; 2D, 2E, 2G, 311 and 3J; 2D, 2E. 2G, 31 and 3J; 2D, 21E, 3H, 31 and 3J; 2E, 21F, 2G, 31 and 31; 2E, 21, 2G, 31H and 3J; 211, 21, 2G, 31 and 3J; 2E, 21, 3H, 31 and 3J; or 2F, 2G, 3H, 31 and 3J. In some embodiments, the non-naturally occurring eukaryotic organism, comprises five or more exogenous nucleic acids, wherein each of the five or more exogenous nucleic acids encodes a different acetyl-CoA pathway enzyme. [001071 In yet other embodiments, the acetyl-CoA pathway comprises: 2A, 2B3, 2C, 2D, 2E and 2F;2A, 2B, 2C, 2D, 2E and 2G; 2A, 21B, 2C, 2D, 2E and 3H; 2A, 2B, 2C, 2D, 2E and 31; 2A, 2B, 2C, 2D, 2E and 3J; 2A, 213, 2C, 2D, 2F and 2G; 2A, 213, 2C, 21, 2F and 3H; 2A, 2B, 2C, 2D,1 F and 31; 2A, 2B, 2C, 2D, 2F and 311; 2A, 2B, 2C, 2D, 2G and 311; 2A, 2B, 2C, 21D, 2G and 31; 2k, 2B, 2C, 21, 2G and 31; 2A, 2B, 2C, 21, 3H and 31; 2A, 213, 2C, 21, 3H and 3J; 2A, 2B. 2C, 2D, 31 and 3J; 2A, 213, 2C, 2E 2F and 2G; 2A, 2B, 2C, 2E, 2F and 311; 2A 213, 2C, 2E, 21 and 31; 2A, 213, 2C, 2E,12F and 31; 2A, 2B, 2C, 21, 2G and 3Hf; 2A, 213, 2C, 2E, 2G and 31; 2A 2B, 2C, 2E, 2G and 3J; 2A, 213, 2C, 2E, 3H and 31; 2A, 213, 2C, 2E 31 and 3J 2A, 2B, 2C, 2E, 3I and 3]; 2A, 213, 2C, 21, 2G and 3H; 2A, 213, 2C, 21, 2G and 31; 2A, 213, 2C, 21, 20 and 3J; 2A, 2B, 2C, 2F, 3H and 3I;2A, 2B, 2C, 2F, 31 Hand 3J; 2A, 2B, 2C, 2F, 31 and 3J; 2A, 2B, 2C, 20, 311 and 31; 2A, 2B,1 C, 2G, 31- and 33; 2A, 2B1, 2C, 2G, 31 and 3J; 2A, 2B, 2C, 3R, 31 and 3J; 2A, 2B, 2D, 2E, 3H and 31; 2A, 2B, 2D, 2E, 3H and 3J; 2A, 2B, 2D, 2E, 31 and 3]; 2A, 213, 2D,1 F 2G and 311; 2A, 2B, 2D, 2, 2G and 31; 2A, 2B, 2D, 2, 2G and 33; 2A, 2B, 2D, 2F, 3H and 31; A, 213, 21, 2F, 3H and 3J; 2A, 213, 21, 21, 31 and 3J; 2A, 213, 21, 2G, 3H and 31; 2A, 2B, 2D, 2G, 3H and 3J; 2A,2B, 12 21G, 31 and 3J; 2A, 2B, 21 311, 31 and 3J; 2A, 2B. 2E, 213, 2 and 3; 2A, 213, " 2F, 2G and 31; 2A, 2, 2E1 213, 2 and 33; 2A, 213,2E, 2F, 311 and 31; 2A, 2B, 2E, 2F, 3H and 3J; 2A, 213, 2E, 2F, 31 and 3J; 2A, 213, 2E, 2G, 3H and 31; 2A, 2B, 21E, 2G, 311 and 3J; 2A, 21B, 2E, 2G, 31 and 3J; 2A, 2B, 2E, 3H, 31 and 33; 2A 2B, F 2G, 311 and 31; 2k, 2B, 2F, 2G, 31H and 3J; 2A, 2B, 2F, 2G, 31 and 3J; 2A,2B, 2F, 3H, 31 and 3]; 2A, 2B,2G, 311, 31 and 3J; 2A, 2C, 2D, 2E, 2F and 2G; 2A, 2C, 2D, 21E, 2F and 3W; 2A, 2C, 2D, 2E, -51- 2F and 31; 2A, 2C 2D, 2E, 2F and 3J; 2A, 2C, 2D, 2E, 2G and 3H; 2A, 2C, 2D, 2E, 2G and 31; 2A, 2C, 2D, 2E, 2G and 33; 2A, 2C, 2D, 2E, 31 and 31; 2A, 2C, 2D, 21E, 31 and 3.; 2A, 2C 21), 2E, 31 and 3J; 2A, 2C, 2D, 2F, 2G and 3H; 2A, 2C, 2D, 2F, 2G and 31; 2A, 2C, 2D, 2F, 2G and 33; 2A, 2C, 2D, 2F, 311 and 31; 2A, 2C, 2D, 2F, 31 and 3; 2A, 2C, 2D, 2F, 31 and 3J; 2A, 2C, 2D, 20, 3H and 31; 2A, 2C, 2D, 2G, 3H and 3J; 2A, 2C, 2D, 2G, 31 and 3J; 2A, 2C, 2D, 3H, 31 and 33; 2A, 2C, 2E, 2F, 2G and 311; 2A, 2C, 2E, 2F, 2G and 31; 2A, 2C, 2E, 2F 2G and 3J; 2A, 2C,, , 2F, 3H and 3; 2A, 2C, 2E, 2F, 3MH and 3J; 2A, 2C, 2E, 2F, 31 and 33; 2A, 2C, 2E, 2G, 3H and 3; 2A, 2C, 2E, 2G, 3H and 3J; 2A, 2C, 2E, 2G, 31 and 3J; 2A, 2C, 2E, 3H, 31 and 3J; 2A, 2C, 2F, 2G, 3H and 31: 2A, 2C, 2F, 2G, 3H and 3J; 2A, 2C, 2F, 2G, 31 and 31; 2A, 2C, 21F, 3H, 31 and 3J; 2A, 2C, 2G, 3H, 31 and 3J; 2A, 2D, 2E, 2F, 2G and 3H; 2A, 2D, 2E, 2F, 2G and 3]; 2A, 2D, 2E, 2F, 2G and 33; 2A, 2D, 2E, 2F, 31 and 31; 2A, 21, 2E2F, 3H and 33; 2A, 2D, 2E, 2F, 31 and 3J; 2A, 2D, 2E, 2G, 3H and 31; 2A, 2D, 2E, 2G, 3H and 3J; 2A, 2D, 2E, 2G, 31 and 3J; 2A, 2D, 2E, 3H, 31 and 33; 2A, 2D, 2F, 2G, 3H and 31; 2A, 2D, 2F, 2G, 311 and 33; 2A, 2D, 2F, 2G, 31 and 3J; 2A, 2D, 2F, 31H, 31 and 3J; 2A, 2D, 2G, 3H, 31 and 3J; 2A, 2E, 2F, 2G, 3H and 31 2A, 2E, 2F, 2G, 3H and 3J; 2A, 2E, 2F, 2G, 31 and 3J; 2A, 2E, 2F, 311, 31 and 3J; 2A, 2E, 20, 3H, 31 and 3J; 2A, 2F, 2G 3H-, 31 and 3J; 2B, 2C, 2D, 213 and 2G; 2B, 2C, 23, 2E, 2F and 3H; 2B, 2C, 2D, 2E, 2F and 3I 2B, 2C, 2D, 2E, 2F and 3J; 2B, 2C, 2D, 2E, 2G and 3H; 213, 2C, 21D, 21, 2G and 31; 2B, 2C, 213, 2E, 2G and 3J; 213, 2C, D, 2E, 31H and 31; 21, 2C, 2D, 2E, 3H and 31; 2B, 2C, 2D, 2E, 31 and 3J; 2B, 2C, 2D, 2F, 2G and 3H; 2B, 2C, 2D, 2F, 20 and 31; 2B, 2C, 2D, 2F, 2G and 33; 2B, 2C, 2D, 2F, 311 and 31; 2B, 2C, 2D, 2F, 311 and 3J; 2B, 2C, 2D, 2F, 31 and 3J; 2B, 2C, 2D, 2G, 3H and 31; 2B, 2C, 2D, 2G, 3H and 33; 2B, 2C, 2D, 2G, 31 and 3J; 2B, 2C, 2D, 3RV, 31 and 3J; 2B, 2C, 2E, 2F, 2G and 3H; 2B, 22E, 213 213 2G and 31; 2B, 2C, 2E, 2F, 2G and 33; 2B, 2C, 2E, 2F, 3H and 31; 2B, 2C, 2E, 2F, 3H and 3J; 2B, 2C, 2E, 2F, 31 and 3J; 2B, 2C, 2E, 2G, 3H and 31; 2B, 2C, 2E, 2G, 3H and 3J; 2B, 2C, 2E, 2G, 31 and 3J; 2B, 2C, 2E, 31-1, 31 and 3; 2B, 2C, 2F, 2G, 31 and 31; 213,21 213, 2G, 31-1 and 3J; 213,2C, 213, 2(, 31 and 3J; 2B, 2C, 2F, 3H, 31 and 3J 2B, 2C, 2G, 3H, 31 and 3J; 2B, 2D, 2E, 2F, 2G and 3H; 2B, 2D, 2E, 2F, 2G and 31; 2B, 2D, 2E, 2F, 2G and 3J; 213, 21), 21E, 2F, 31-1 and 31; 213, 21), 2E, 2F, 3H and 3J; 2B, 2D, 2E, 2F, 31 and 33; 2B, 2D, 2E, 2G, 3H and 31; 2B, 2D, 2E, 2G, 3H and 33; 2B, 2D, 2E, 2G, 31 and 3J; 2B, 2D, 2E, 31H, 31 and 33; 2B, 2D, 2F, 2G, 31 and 31; 2B, 2D, 2F, 2G, 3H and 3J; 2B, 2D, 2F, 2G, 31 and 33; 2B, 2D, 2F, 31, 31 and 3J; 2B, 2E, 2F, 2G, 311 and 31; -52- 2B, 2E, 2F, 2G, 3H and 3J; 2B, 2E, 2F, 2G, 31 and 3J; 2B, 2E, 2F, 3H, 31 and 3J; 2B, 2E, 2G, 31-1, 31 and 3J; 2B, 2F, 2G, 31-1, 31 and 3J; 2C, 21), 2E, 2F, 31 and 31; 2(C 2D, 2E, 2F, 3H- and 3J; 2C, 2D, 2E, 2F, 31 and 3J; 2C, 2D, 2E, 2G, 3 H and 31; 2C, 2D, 2E 2G, 3H and 3J; 2C, 213, 2E, 2G, 31 and 3J; 2C, 2D, 2E, 31], 31 and 3J; 2C, 2D, 2F, 2G, 311 and 31; 2C, 2D, 2F, 2G, 311 and 3J; 2C, 21D, 2F, 2G, 31 and 3J; 2C, 213, 2F, 3H, 31 and 3J; 2C, 2D, 2G, 3H, 31 and 3J; 2D, 2E, 2F, 2G, 31 and 31; 2D, 2E, 2F, 2G, 311 and 3J; 2D, 2E, 2F, 2G 31 and 3J; 2D, , 2F, 31H, 31 and 3J; 21, 2E, 2G, 3H, 31 and 31; or 2E, 2F, 2G, 31-1, 31 and 3J. In some embodiments, the non naturally occurring eukaryotic organism, comprises six or more exogenous nucleic acids, wherein each of the six or more exogenous nucleic acids encodes a different acetyl-CoA pathway enzyme. [001081 In some embodiments, the acetyl-CoA pathway comprises: 2A, 2B, 2C, 2D, 2E, 2F and 2G; 2A, 2B, 2C, 213 2E, 2F and 3H'; 2A, 2, 2C, 2D, 2E, 2F and 31; 2A, 2B, 2C, 2D, 2E, 2F and 3J; 2A, 213, 2C, 2D, 2E, 2G and 3H; 2A, 2B, 2C, 2D, 2E, 2G and 31; 2A, 2B, 2C, 2D, 2E 2G and 3J; 2A, 2B, 2C, 2D, 2E, 311 and 31; 2A, 213, 2C 2D, 2E, 311 and 3J; 2A, 213, 2C, 2D, 2E, 31 and 3J; 2A, 213, 2C, 2D, 2F, 2G and 314; 2A, 2B, 2C 2D, 2F, 2G and 31; 2A, 213, 2C, 213, 2F, 2G and 3J; 2A, 213, 2C, 2D, 2F, 3H and 31; 2A, 2B, 2C, 2D, 2F, 3H and 3J; 2A, 213, 2C, 2D, 2F, 31 and 3 2A, 213, 2, 21), 2F, 3H and 31' 2A, 2B, 2C, 2D, 2F, 31] and 3; 2A, 213, 2C, 21), 2G, 31-I and 31; 2A, 213, 2C, 2D, 2G, 3H and 3J; 2A, 213 2C, 2D, 2G, 31 and 3J; 2A, 213, 2C 21, 314, 31 and 3J; 2A, 2B, 2C, 2E, 2F, 2G and 3Ff; 2A, 2B, 2C, 2E, 2F, 2G and 31; 2A, 21, 2C, 2E, 2F, 2G and 3J; 2A, 213, 2(7, 2E, 2F, 3H and 31; 2A, 2B, 2C, 2E, 2F, 3H and 3J; 2A, 2B, 2C, 2E, 2F, 31 and 3J; 2A, 2B, 2C, 2E, 2G, 31 and 31; 2A, 2B 2C, 2E, 2G, 3H and 3J; 2A, 2B, 2C, 2E, 2G, 31 and 3J; 2A, 213, 2C, 2E, 3H, 31 and 3J; 2A, 213, 2C, 2F, 2G, 3 H and 31; 2A, 2B, 2C, 2F, 2G, 3H and 3J; 2A, 2B, 2C, 2F, 20, 31 and 3J; 2A, 2B, 2C, 2F, 3H, 31 and 3J; 2A, 213, 2C, 2G, 314, 31 and 3J; 2A, 2B, 21), 2E, 3Ff, 31 and 3J; 2A, 213, 21), 21, 2G, 311 and 31; 2A, 2B, 21), 2F, 2G, 3[H and 3J; 2A, 213, 2, 2F, 2G, 31 and 3J; 2A, 2B, 2D, 21±, 314, 31 and 3J; 2A, 2B, 2D, 2G, 3H, 31 and 3; 2A, 213, 2E, 2F, 2G, 3Ff and 31; 2A, 213, 2E, 2F, 20, 3F and 3J; 2A, 213, 21E, 2F, 2G., 31 and 3J 2A, 2B, 2E, 2F, 31, 31 and 31 2A, 2B, 2E, 2G, 3H, 31 and 3J; 2A, 2B, 2F, 2G, 3H, 31 and 3J; 2A, 2C, 213, 2E, 2F, 2G and 3H; 2A, 2C, 2D, 213 21F, 2G and 31; 2A, 2C, 2D, 1E 2F, 2G and 3J; 2A, 2C, 2LD, 2E, 2F, 31] and 31; 2A 2C, 21, 2E, 2F, 31] and 3J; 2A, 2C, 213, 2E, 2F, 31 and 3; 2A, 2C, 2D, 2E, 2G, 3H and 31; 2A, (7 'P 2E, 2G, 311 and 3J; 2A, 2C, 213, 2E, 2G, 31 -53and 3J; 2A, 2C, 2D, 2E, 3H, 31 and 3J; 2A, 2C, 2D, 2F, 2G, 3H and 31; 2A, 2C, 2D,2F, 2G, 3H and 33; 2A, 2C, 2D, 2F, 2G, 31 and 3J; 2A, 2C, 2D, 21, 3H, 31 and 3J; 2A, 2C, 2D, 2G, 3H, 31 and 3J; 2A, 2C, 2E, 2F, 2G, 31H and 31; 2A, 2C, 2E 2F, 2G, 31H and 3J; 2A, 2C, 2E, 2F, 2G, 31 and 3J; 2A, 2C, 2E, 2F, 31, 31 and 3J; 2A, 2C, 2E, 2G, 311, 31 and 3J; 2A, 2C, 2F, 2G, 31H, 31 and 3J; 2A, 2D, 2E, 2F, 2G, 3H and 31; 2A, 2D, 2E, 2F, 2G, 3H and 3J; 2A, 2D, 2E, 2F, 2G, 31 and 33; 2A, 2D, 2E, 2F, 311, 31 and 3J; 2A, 2D, 2E, 2G, 311, 31 and 3J; 2A, 2D, 2F, 2G, 311, 31 and 3 2A, 2E, 2F, 2G, 3H, 31 and 3]; 2B, 2(, 2D, 2E, 2F, 2G and 3H; 2B, 2C, 2D, 2E, 2F, 2G and 31; 2B, 2C, 2D, 2E, 2F, 2G and 3J; 2B, 2C, 21D 2E, 2F, 311 and 31; 23, 2C, 2D, 2E, 2F, 3H and 3J; 2B, 2C, 21 2E, 2F, 31 and 31 2B, 2C, 2D, 21E, 2G, 31-1 and 31; 213, 2, 21), 2E, 2G, 331 and 3J; 2B, 2C, 2D, 2E, 2G, 31 and 31 2B, 2C, 2D, 2E, 3H, 31 and 3J; 2B, 2C, 2D, 2F, 2G, 3H and 31; 213, 2C, 2D, 2F, 2G, 3H and 3J; 2B, 2C, 2D, 2F, 2G, 31 and 3J; 213, 2(, 2D, 21, 31, 31 and 3J; 2B, 2C, 2D, 2G, 3H, 31 and 3J; 23, 2C, 2E 2F, 2G, 3H and 31; 2B, 2C, 2E, 2F, 2G, 3H and 3J; 2B, 2C, 2E, 2F, 2G, 31 and 33; 2B, , (7 2E, 2F, 311, 31 and 3J; 2B, 2, 2E, 2G, 311, 31 and 3J; 2B, 2C, 2F, 2G, 3H, 31 and 3.1; 23, 2D, 2E, 2F, 2G, 3H and 31; 23, 2D, 2E, 2F, 2G, 3H and 3J; 2B, 2D, 2E, 2F, 2G, 31 and 3J; 2B, 2D, 2E, 2F, 311, 3 and 3J; 2B, 2D, 2E, 2G, 311, 31 and 3J; 2B, 2D, 21F, 2G, 3H, 31 and 3]; 2B, 2E, 2F, 2G, 31, 31 and 3.1; 2(, 21 2E, 2F, 31, 31 and 3]; 2C, 2D, 2E, 2G, 3H, 31 and 31 2C, 2D, 2F, 2G, 311, 31 and 3J; or 2D, 2E, 2F, 2G, 3H, 31 and 3J. In some embodiments, the non-naturally occurring eukaryotic organ ism, comprises seven or more exogenous nucleic acids, wherein each of the seven or more exogenous nucleic acids encodes a different acetyl-CoA pathway enzyme. [00109] In certain embodiments, the acetyl-CoA pathway comprises: 2A, 2B, 2C, 2D, 2E, 2F, 2G and 311; 2A, 2B, 2C, 2D, 2E, 2F, 2G and 31; 2A, 23, 2C, 2D, 2E, 2F, 2G and 3J; 2A, 23, 2C, 2D, 2E, 21, 311 and 31; 2A, 23, 2C, 2D, 2E, 2F, 3H and 3J; 2A, 2D. 2C, 2D, 2E, 2F, 31 and 3J; 2A, 2B, 2C, 2D, 2E, 2G, 311 and 31; 2A, 213, 2C, 21), 2E, 2G, 31-1 and 3]; 2A, 2B, 2C, 21), 2E, 2G, 31 and 3J; 2A, 2B, 2C, 2D, 2E, 3H, 31 and 3J; 2A, 2B, 2C, 2D, 2F, 2G, 3H and 31; 2A, 23, 2C, 2D, 2F, 2G, 3H and 33; 2A, 213, 2C, 2D, 2F, 2G. 31 and 33; 2A, 213, 2(, 2D, 21, 31H, 31 and 3J; 2A, 2B, 2C, 2D, 2F, 3H, 31 and 3J; 2A, 23, 2C, 2D, 2G, 3H, 31 and 3J; 2A, 2, 2C, 2E, 2F, 2G, 3H and 31; 2A, 23, 2C, 2E, 2F, 2G, 3H and 3J; 2A, 23, 2E, 2 23 2G, 31 and 3J; 2A, 23, 2C, 2E, 2F, 3H, 31 and 3]; 2A, 2B, 2C, 2E, 2G, 3H, 31 and 3J; 2A, 23, 2C, 2 F, 2G, 3H, 31 and 3J; 2A, 2B, 2D, 2F, 2G, 31H, 31 and 3J; 2A, 23, 2E, 2F, 2G, 311, 31 and 3J; 2A, 2C, 2D, 2E, 2F, -54- 2G, 3H and 31 2A, 2C 2D, 2E, 2F, 2G, 3H and 3J 2A, 2C, 2D, 2K 2F, 2G, 31 and 3J; 2A, 2C, 2D, 2E, 2F, 3H, 31 and 31; 2A, 2C, 2D, 2E, 2G, 31, 31 and 3J; 2A, 2C, 21), 2F,2G, 3H, 31 and 3J; 2A, 2C, 2E, 2F, 2G, 3H, 31 and 3J; 2A, 2D, 2E, 2F, 2G, 3H, 31 and 3J; 213, 2C, 2D, 2E, 2F, 2G, 311 and 3;, , 2B,2C,2D 2E, 2F, 2G, 3H and 33; 21B, 2C, 2D, 2 , 2 2G, 31 and 3J; 2B, 2C, 2D, 2E, 2F, 3H, 31 and 3J; 2B, 2C, 2D, 2E 2G, 3H, 31 and 3J; 2B, 2C, 2D, 2F, 2G, 3H, 31 and 3J; 2B, 2C, 2E, 2F, 2G, 31, 31 and 3J; or 2B 2D, 2E. 2F, 2G, 3, 31 and 3J. In some embodiments, the non-naturally occurring eukaryotic organism, comprises eight or more exogenous nucleic acids. wherein each of the eight or more exogenous nucleic acids encodes a different acetvl-CoA pathway enzyme. 1001101 In some embodiments, the acetyl-CoA pathway comprises 2A, 21, 2C, 21), , 2F, 2G, 3H and 31; 2A, 2B, 2C, 2D, 2E, 2 2G, 311 and 3J; 2A, 213, 2C, 2D, 2E, 2F, 2G, 31 and 3J; 2A, 21B, 2C, 2D, 2E,' 21, 311, 31 and 3J; 2A, 2B, 2C, 2D, 2E, 2G, 3H, 31 and 33; 2A, 2B, 2C, 2D, 2F, 2G, 3H, 31 and 3J; 2A, 2B, 2C, 2E, 2F, 2G, 3H, 31 and 3J; 2A, 2C, 2D , 2E 2F, 2G, 3H, 3I and 3J; or 2B, 2C, 2D 2E, 2, 22G, 311, 31 and 3J. In some enbodiments, the non-naturally occurring eukaryotic organism, comprises nine or more exogenous nucleic acids, wherein each of the nine or more exogenous nucleic acids encodes a different acetyl-CoA pathway enzyme. [001111 In other embodiments, the acetyl-CoA pathway comprises 2A 213, 2C, 2D, 2E, 2F, 2(, 311, 3 and 3J. In some embodiments, the non-naturally occurring eukaryotic organism, comprises ten or more exogenous nucleic acids, wherein each of the ten or more exogenous nucleic acids encodes a different acetyl-CoA pathway enzyme. [001121 In certain embodiments, the acetyi-CoA pathway comprises 5A, 5B, 5C, 5D, 5E, 5F, 5G, 5H, 51, 5J or any combination of 5A, 5B, 5C, 5D, 15E, 5F, 5G, 5H, 51, or 5J thereof, wherein 5A is a pyruvate oxidase (acetate forming); 5B is an acetyl-CoA synthetase, ligase or transferase; SC is an acetate kinase; 5D is a phosphotransacetylase; 5I is a pyruvate decarboxylase; SF is an acetaldehyde dehydrogenase; 5G is a pyruvate oxidase (acetyl-phosphate forming); 5H is a pyruvate dehydrogenase, pyruvate:ferredoxin oxidoreductase or pyruvate formate lyase; 51 acetaldehyde dehydrogenase (acylating); and 5J is a threonine aldolase. In certain embodiments, SB is an acetyl-CoA synthetase. In another embodiment, 5B is an acetyl-CoA ligase. In other embodiments, 5B is an acetyl-CoA transferase. In some embodiments, 5H is a pyruvate -55dehydrogenase. In other embodiments, 5H is a pyruvate:ferredoxin oxidoreductase. In yet other embodiments, 51-1 is a pyruvate formate lyase. [00113] In some embodiments, the acetyl-CoA pathway is an acetyl-CoA pathway depicted in FIG. 5. In a specific embodiment, the acetyl-CoA pathway comprises 5A and 5B. In another embodiment, the acetvl-CoA pathway comprises 5A, 5C and 5D. In another embodiment, the acetyl-CoA pathway comprises 5G and 5D. In yet another specific embodiment, the acetyl-CoA pathway comprises 5E, 5F, 5C and 5D. In other embodiments, the acetyl-CoA pathway comprises 5J and 5L In some embodiments, the acetyl-CoA pathway comprises 5J, 5F and 5B. In yet other specific embodiments, the acetyl-CoA pathway comprises 5H. [001141 In one embodiment, the acetyl-CoA pathway comprises SA. In another embodiment, the acetyl-CoA pathway comprises 513. In some embodiments, the acetyl-CoA pathway comprises 5C. In some embodiments, the acetyl-CoA pathway comprises 5D. In some embodiments, the acetyl-Co-A pathway comprises 5E. In other embodiments, the acetyl-CoA pathway comprises 5F. In yet other embodiments, the acetyl-CoA pathway comprises 5G. In sonic embodiments, the acetyl-CoA pathway comprises 5G. In another embodiment, the acetyl CoA pathway comprises 5. In some embodiments, the acetyl-CoA pathway comprises 51. In some embodiments, the acetyl-CoA pathway comprises 5J. In some embodiments, the non naturally occurring eukaryotic organism, comprises one or more exogenous nucleic acids, wherein each of the one or more exogenous nucleic acids encodes a different acetyl-CoA pathway enzyme. [001151 In sonie embodiments, the acetyl-CoA pathway comprises: 5A and 5B: 5A and 5C; 5A and 5D; 5A and 5E; 5A and 5F: 5A and 5G; 5A and 5H; 5A and 5I; 5A and 5J; 5B and 5C; 5B and 5D; 5B and 5E; 5B and 5F; 5B and 5G; 5B and Sri; 5B and 5I; 5B and Si: 5C and 5D; SC and 5E: SC and SF; SC and 5G; SC and SH; SC and 5I SC and SJ; SD and SE; SD and SF; 5) and 5G SD and SE; 5D and 5F; SD and 5G; 5D and 5H; 5D and SI; 5D and 5J; 5E and 5F: 5E and 5G; 5F and 5H; 5F and 51; 5E and 5i; 5F and 5G; 5F and 5FH; 5F and 5I; 5F and 5i; 5G and H;C 5G and SI 5G and 5J; 5H and 5I: 5H and 5J; or 5I and 5J. In some embodiments, the non naturally occurring eukaryotic organism comprises two or more exogenous nucleic acids, -56wherein each of the two or more exogenous nucleic acids encodes a different acetyl-CoA pathway enzyme. [00116] In other embodiments, the acetyl-CoA pathway comprises: 5A, 5B and 5C; 5A, 5B and 5D; 5A, 5B and 5E; 5A, 5B and 5F; 5A, 5B and 5G; 5A, 5B and SH; 5A, 5B and 5I; 5A, 5B and 5J; 5A, 5C and 5D; 5A, 5C and 5E; 5A, 5C and 5F; 5A, 5C and 5G; 5A, 5C and 511; 5A, 5C and 51; 5A, 5C and 5i; 5A, 5D and 5E; 5A, 5D and 5F; 5A, 5D and 5G; 5A, 5D and 5H; 5A, 5D and SI; 5A, 5D and 5J; 5A, 5E and 5F; 5A, SE and 5G; 5A, 5E and 511; 5A, 5E and SI; 5A, 5E and 5i; 5A, 5F and 5G; 5A, 5F and 5H; 5A, 5F and 51; 5A, 5F and 5i; 5B, 5C and 5D; SB, 5C and 5E; 5B, SC and 5F; 5B, 5C and 5G; 5B, 5C and 511; SB, 5C and 5I; 5B, 5C and J; 5B. 5D and 5E; SB, 5D and 5F; SB, 5D and 5G; 5B, 5D and 5H; 5B, 5D and 5; SB, 5D and 5i; 5B, 5i: and 5F; 5B, 5E and SC; SB, 5E and 5H; 5B, SE and 5I; 5B, SE and 5J; SB, 5F and 5G; 5B, 5F and 5H; 5B, 5F and 5I; 5B, 5F and 5J; 5C, 5D and 5E; 5C, 5D and 5F; 5C, 5D and 5C; 5C, 5D and 5H; 5C, 5D and 5I; 5C, 5D and 5J; 5C, 5E and 5F; 5C, 5E and 5G; 5C, 5E and 5H; 5C, 5E and 51; 5C, 5E and 5J; 5C, 5F and 5G; SC, 5F and 5ri; 5C, 5F and 51; 5C, 5F and 5J; 5D, 5E and 5F; 5D, 5E and 5G; 5D, 5E and 5H; 5D, 5E and 5I; 5D, 5E and 5J; 5D, 5F and 5G; 5D, 5F and 51; 5D, SF and 5I; SD, SF and 5J; SD, 5G and 511; 5D, 5G and 5I; SD, 5G and 5J; 5D, 5E and 5F; 5D, 5E and 5G; 5D, 5E and 5H; SD, 5E and 5I; 5D, 5E and 5i; 5), 5F and 5G; 5D,5F and 5H; SD, 5F and 5I; 5D. 5F and 5J; 5D, 5G and 5H; 5D, 5G and 5I; 5D, 5G and 5J; 5D, 5H and 5I; 5D, 51 and 5i; 5), 51 and 5i; 5E, 5F and 5G; 5E, 5F and 5N; 5E, 5F and 5I; 5E, 5F and 5J; 5F, 5G and 5H; 5F, 5G and 5I; 5F, 5G and 5J; 5G, 5H and 5I; 5G, 5H and 5J; or 5H, 5I and 5. In some embodiments, the non-naturally occurring eukaryotic organism comprises three or more exogenous nucleic acids, wherein each of the three or more exogenous nucleic acids encodes a different acetyl-CoA pathway enzyme. [001171 In certain embodiments, the acetyl CoA pathway comprises: SA, 5B, 5C and 5D; 5A, 5B, 5C and SE; 5A, 5B, 5C and 5F; 5A, 5B, 5C and 5G; 5A, 5B, 5C and 5H; 5A, 5B, 5C and 51; 5A, SB, 5C and 5J; 5A, 5B, 5D and SE; 5A, 5B, 5D and 5F; 5A, 5B, 5D and 5G; 5A, 5B, 5D and 51; 5A, 5B, 5D and 51; 5A, 5B, 5D and 5J; 5A, 5B, 5E and 5F; 5A, 5B, 5E and 5G; 5A, 5B, 5E and 5H; 5A, 5B, 5E and 5I; 5A, 5B, 5E and 5i; 5A, 5B, 5F and 5G; 5A, 5B, 5F and 5H; 5A, 5B, 5F and 51; 5A, 5B, 5F and 5J; 5A, 5B, 5G and 5N; 5A, 5B, 5G and 51; 5A, 5B, 5G and 5J; 5A, -57- 5B, 5H and 51; 5A, 5B, 5H and 5J; 5A, 5B, SI and 5J; 5A, SC, 5D and 5E; 5A, 5C, 5D and 5F; SA, 5C, 5D and 5G; 5A, 5C, 5D and 5H; 5A, 5C, SD and 51; 5A, SC, SD and 5J; 5A, 5 C,5E and 5F: 5A, 5C, 5E and 5G; 5A, 5C, 5E and 5H; 5A, 5C, 5E and 51; 5A, 5C, 5E and J; 5A, 5C, 5F and 5G;S A, 5C, 5F and 511; 5A, 5C, 5F and 5; 5A, 5C, 5F and 5J; 5A, 5C, 5G and 511; 5A, 5C, 5G and 51; 5A, 5C, 5G and 5J; 5A, 5C, 15H and 5I; 5A, 5C, 5H and 5J; 5A, 5C, 5I and J; 5A, SD, 5E and 5F; 5A, 5D, 5E and 5G; 5A, 5D, 5E and 511; 5A, 5D, 5E and 5I; 5A, 5D, 5E and 5; SA, 5D, 5F and 5G; 5A, SD, 5F and 5-I; 5A, 5D, SF and 51; 5A, SD, 5F and 5i; 5A, 5D, SG and 5H; 5A, 5D, 5G and SI; 5A, 5D, SG and 5J; 5A 5D, 51H and SI; 5A, 5D, 5H and 5J; N5A 5D, 5I and 5J; 5A, 5E, 5F and 5G; 5A, 5E, 5F and 5-i; 5A, 5E, 5F and 5I; 5A, 5E, 5F and 5i; 5A, 5E, 5G and 5H; SA, 5E, 5G and SI; 5A, 5E, 5G and 5J; 5A, 5E, 5H and SI; 5A, 5E, 5H and 5J; 5A, SE, 51 and J; 5A, 5F, 5G and 5H; 5A, 5F, 5G and 51; 5A, 5F, 5C and 5i; 5A, 5F, 5N and 51; 5A, 5F, 5H and 5J; 5A, 5F, 5I and 5J; 5A, 5G, 5H and SI: 5A, SG, 5H and 5J; 5A, 5G, 5I and 5J; 5A, 5H, 5f and 5i; 5B, 5C, 5D and 5E; 5B, 5C, 5D and 5F; 5B, 5C, 5D and 5G; 5B, 5C, 5D and Si; 5B, 5C, 5D and 51; 5B, 5C, 5D and 5J; 5B, 5C, 5E and 5F; 5B, 5C, 5E and 5G; 5B, 5C, 5E and 511; 5B, 5C, 5E and 5I; 5B, 5C, 5E and 5J; 5B, 5C, 5F and 5G; 5B, 5C, 5F and Sri; 5B, 5C, 5F and 5I; 5B, 5C, 5F and 5i; 5B, SC, 5G and 511; 5B, 5C, 5G and 51; 5B, 5C, 5G and 5i; 5B, 5C, 5H and 5I; 5B, 5C, 5H and 5J; 5B, SC, 5I and 5J; 5B, SD, 5E and 5F; 5B, 5D, SE and 5G; 5B, 5), 5E and 5H; 5B, 5D, 5E and 51; 5B, 5), 5E and 5J; 5B, 5D, 5F and 5G; 5B, 5), 5F and 5-; SB. SD, 5F and 5I; SB, 5D, 5F and SJ; 5B, 5E, SF and 5G; SB, 5E, 5F and 5H; 5B, 5E, SF and 51; 5B, 5E, 5F and 5J; 5B, 5E, 5G and 51H; 5B, 5E, 5G and 51; 5B, 5E, 5G and 5J; 5B, 5E, 5Hi and 5I; 5B, 5E, 5H and 5J; 5B, 5E, 5I and 5J; 5B, SF, 5G and 15H; 5B, 5F, 5G and 5I; 5B, 5F, 5G and 5J; 5B, 5G, 511 and 51; 5B, 5G, 5H and 5; 5B, 5H, 5I and 5J; 5C, 5D, 5E and 5F; 5C, 5D, 5E and 5G; 5C, 5D, 5E and 5H; 5C, 5D, 5E and 5I; 5C, 5D, 5E and 5J; 5C, 5D, 5F and 5G; 5C, 5D, 5F and 5H; SC, 5D, 5F and SI; 5C. 5D, 5F and 5J; SC, 5D, 5G and 5H; 5C, 5D, SG and 5I; SC, SD, 5G and 5J; 5C, 5D, S-i and 51; 5C, 5D, 5H and 5J; 5C,D, 5I and 5i; SD, 5E, 5F and 5G; SD, 5E. 5F and 5H; 5D, SE, SF and St 5D, SE, 5F and 5J; 5D, 5E, G and 5H; SD, SE. 5G and 5; SD, SE, SO and 5J; 5D, 5E, 5-1 and 51; 5D, 5E, 511 and 5i; 5D, 5E, 5I and 5i; 5E, 5F, 5C and 5H; 5E, 5F, 5G and 5I; 5E, 5F, 5G and 5J; 5E, 5F, 5H and 5I; 5E, 5F, 5H and 5J; 5E, 5F, 5I and 5i; 5F, 5G, 511 and 5I; 5F, 5G, 5H] and 5i; 5F, 5G, 51 and 5J; or 5G, 5], 5I and 5J. In some embodiments, the non-naturally occurring eukaryotic organism comprises four or more -58exogenous nucleic acids, wherein each of the four or more exogenous nucleic acids encodes a different acetyl-CoA pathway enzyme. [00118] In other embodiments, the acetyl CoA pathway comprises: 5A, 5B, 5C, 5D and 5E; 5A, 5B, 5C, 5D and 5F; 5A, 5B, 5C, 5D and 5C; 5A, 5B, 5C, 5D and 5H; 5A, 5B, 5C, 5D and 5I; 5A, 5B, 5C, 5D and 5J; 5A, 5B, 5C, 5E and 5F; 5A, 5B, 5C, 5E and 5G; 5A, 5B, 5C, 5E and 5H; 5A, 5B, 5C, 5E and 5I; 5A, 5B, 5C, 5E and 5J; 5A, 5B, 5C, 5F and 5G; 5A, 5B, 5C, 5F and 5H; 5A, SB, 5C, 5F and 5I; SA, 5B, SC. 5F and 5J; 5A, 5B, 5C, 5G and 5H; 5A, 5B, 5C, 5G and 5I; 5A, 5B, 5C, 5G and 5i; 5A SB, 5C, SH and 51; 5A, 5B, 5C, 51 and 5J; 5A, 5B, SC, SI and 5J; 5A, 5B, 5D, 5E and 5H; 5A, 5B, 5D, 5E and 5I; SA, 5B, 5D, SE and 5J; SA, 5B, 5D, 5F and 5G; 5A, 5B, 5), 5F and 5-1; 5A, 5B, 5D, 5F and 51; 5A SB, D, 5F and 5J; 5A, 5B, 5D, 5G and 51H; 5A, SB, 5D, 5G and SI; 5A, 5B. 5D, 5G and 5J; 5A, 5B, 5D, SH and 5I; 5A, 5B, 5D, 51H and 5J; 5A, 5B, 5D, 51 and 5J; 5A, 5B, 5 E, 5F and 5; 5A, 5B, 5E, 5F and 511; 5A, 5B, 5E, 5F and 51; 5A, 5B, 5E, 5F and 5J; 5A, 5B, 5E, 5G and SH; 5A, 5B, 5E, 5G and SI; 5A, 5B, 5E, 5G and 5J; 5A, 5B, 5E, 5H and 5I; 5A, 5B, 5E, 511 and 5J; 5A, 5, 5E, 51 and 5J; 5A, 5B, 5F, 5G and 5N; 5 1 A, 5B, 5F, 5G and 5I; 5A, 5B, 5F, 5G and 5J; 5A, 5B, 5F, 5H and 5I; 5 1 A, 5B, 5F, 5H and 5J; 5A, 5B, 5F, SI and 5J; 5A, SB, 5G, 5H and SI; 5A, 5B, 5G, 5H and 5J; 5A, 5B, 5G, SI and 5J; SA, 5B, 5-1, S1 and 5J; 5A, SC, 5D, 5E and 5F; 5A, 5C, SD, SF and 5G; 5A, 5C, 5D, SE and 5-I; 5A, 5C, 5D, 5E and 5I; 5A, 5C, 5D, 5E and 5J; 5A, 5C, 5D, 5F and 5G; 5A, 5C, SD, 5F and 5H; 5A, 5C, 5D, 5F and 51; 5A, 5C, 5D, 5F and Si; 5A, SC, 5D, SG and 5-I; 5A, 5C, 5D, 5G and 51; 5A, 5C, 5D, 5G and 5J; 5A, 5C, SD, 5H and 5I; 5A, 5C, 5D, 5H and 5J; 5A, 5C, 5D, 5I and 5J; 5A, 5C, 5E, 5F and 5; 5A, 5C, 5E, 5F and 511; 5A, 5C, 5E, 5F and 51; 5A, 5C, 5E, 5F and 5J; 5A, 5C, 5E, 5G and 5H; 5A, 5C, 5E, 5G and 51; 5A, 5C, 5E, 5G and 5J; 5A, 5C, 5E, 5H and 5; 5A, 5C, 5E, 5H] and 5J; 5A, 5C, 5E, 5I and 5J; 5A, 5C, 5F, 5G and 5H; 5A, 5C, 5F, 5G and 51; 5A, 5C, 5F, G and 5J; 5A, 5C, 5F, 5-I and 5I; 5A, 5C, 5F, 5-I and 5J; 5A, SC, 5F, 51 and 5J; 5A, SC, 5G, 5H and SI; 5A, 5C, 5G, 5H and 5J; 5A, 5C, 5G, 5I and 5J; 5A, 5C, 5H, 5I and SJ; SA, 5D, 5E, 5F and 5G; 5A, 5D, 5E, 5F and 51; 5 5D, 5E, 5F and 51; 5A, 5D, 5E, 5F and 5i; 5A, 5D, 5E, 5G and 511; 5A, 5D. 5E. 5G and 5I; 5A, 5D, 5E, 5G and 5J 5A, SD, 5E, 5H and 5I; 5A, 5D, 5E, 511 and 5J; 5A, 5D, 5E, 51 and 5J; 5A, 5D, 5F, 5G and 5H; 5A, 5D, 5F, 5G and 5I; 5A, 5D, 5F, 5G and 5J; 5A, 5D, 5F, 5H and 5I; 5A, 5D, 5F, 5H and 5J; 5A, 5D, 5F, 51 and 5J; 5A, 5D, 5G, 5-I and 51; 5A, 5D, 5, 511 and 5; 5A, 5D, 5, 51 and 5J; 5A, 5D, 5H, 51 and 5; -59- 5A, SE, 5F, 5G and 5H; 5A, 5E, 5F, 5G and 51; 5A, 5E, 5F, 5G and 5J; 5A, 5E, 5F, 5H and 51; 5A, 5E, 5F, 5H and 5J; 5, 5E, 5F, 5I and 5J; 5A, 5E, 5G, 5 and 5; 5A, 5E, 5G, 5i and 5J; 5A, 5E, 5G, 5I and 5J; 5A, 5E, 5H, SI and 5; 5A, SF, 5G, 5H and 51; 5A, 5F, 5G, 5H and 5J; 5A, 5F, Q5G, SI and 5J; 5A, SF, 5H, 51 and 5; 5A, S, 511, 51 and 5J; SB, 5C, SD, SE and SF; SB, 5C, 5D, 5E and 5C 5B, 5C, 5D, SE and 5H; 5B, 5C, 5D, 5E and 51; 5B, 5C, 5D, 5E and 5J; 5B, 5C, 5D, 5F and 5G; B, 5C, SD, 5F and 5H1; 5B, SC, 5D, 5F and 5I; SB, 5C, 5D, SF and Si; 5B, 5C, 5D, 5G and S1; 5B, 5C, 5D, 5G and 5I; 5B, 5C, 5D, 5G and 5J; 5B, 5C, 5D, 5H and 5I; 5B, 5C, 5D, 5H and 5J; 5B, SC, 5D, SI and 5; 5B, 5C, 5E, 5F and SG; 5B, 5C, 5E, 5F and 5H; 5B, 5C, 5E, SF and 5; 5B, 5C, 5E, 5F and 5J; 5B, 5C, 5E, 5C and 5H; 5B, 5C, 5E, SC and 51; SB, 5C, 5E, 5G and 5J; 5B, 5C, 5E, 5H and SI; 5B, SC, 5E, 5H and 5J; 5B, 5C, SE, 5I and 5J; 5B, 5C, 5F, 5G and 5H; 5B, 5C, 5F, 5G and 51; 5B, 5C, 5F, 5G and 5J; 5B, 5C, 5F, 5H and 5I; 5B, 5C, 5F, 5H and 5J; 5B, 5C, 5F, 5I and 5J; 5B, 5C, 5G, 5H and 5N; 5B, 5C, 5G, 5H and 5J; 5B, 5C, 5G, SI and 5J; SB. 5C, S1, 5I and 5J; SB, 5D, 5E, SF and SG; SB, 5D, 5E, SF and SH; 5B, 5D, 5E, SF and 5; 5B, 5D, 5E, SF and 5J; 5B, 5D, 5E, 5G and 5H; 5B, 5D, 5E, 5G and 5I; 5B, 5D, SE, 5G and 5; 5B, SD, SE, SH and 5I; SB. 5D, 5E, 511 and 5J; SB. 5D, 5E, 51 and 5; 5B, 5D, 5F, 5G and 5H; 5B, 5D, 5F, 5G and 51; 5B, 5D, 5F, 5G and 5J; SB, 5D, 5F, SH and 5; 5B, 5D, 5F, 5H and 5J; 5B, 5D, 5F, SI and 5J; 5B, 5E, 5F, 5G and SH; 5B, 5E, 5F, 5G and 5I; 5B, 5E, 5F, 5G and 5J; SB, 5E, 5F, 5H and 5; 5B, 5E, 5F, 5H and Si; 5B, 5E, 5F, 5I and 5i; 5B, 5E, 5G, 5H and 5I; 5B, 5E, 5G, 5H and 5J; 5B, 5E, 5G, 5I and 5J; 5B, 5E, 5H, 5I and 5J; 5B, 5F, 5G, SH and SI; 5B, SF, 5G, 5H and SJ; SB, 5F, SC, SI and 5J; SB. 5G, 51, 51 and 5J; 5C, SD, 5E. 5F and 5H; 5C, 5D. 5E, SF and 5I; 5C, 5D, 5E, 5F and 5J; 5C, SD, 5E, 5G and SH; 5C, 5D, 5E, 5G and SI: 5C, 5D, 5E, 5G and 5; SC, 5D, 5E, SF and 5I; 5C, 5D, 5E, 5H and 5J; 5C, 5D, 5E, 51 and 5J; 5C, 5D, 5F, 5G and 5H; 5C, 5D, 5F, 5G and 5I 5C, 5D, 5F, 5G and 5J; 5C, 5D, 5F, 5H and 5I: 5C, 5D, 5F, 5H and 5J; 5C, 5D, 5F, 5I and 5J; 5C, 5D, 5G, SH and 5I; 5C, 5D, 5G, 5H and Si; 5C, 5D, 5G, 5I and 5i; SC, 5D, 5N, 5I and 5J; 5D, 5E, 5F, 5G and 51; 5D, 5E, 5F, 5C and 5I; 5D, 5E, 5F, 5G and 5J; 5D, 5E, SF, 5H and 5I; 5D, SE, 5F, 5H and J; 5D, SE, SF, 5I and 5; 5D, 5E, 5G, 5H and 51; 5D, SE, 5G, SH and 5i; 5D, SE. 5G, 51 and 5J; 5D, 5E, 51, 51 and 5J; 5E, 5F, 5G, 5H and SI; 5E, 5F, 5G, 5H and 5I; 5E, 5F, 5G, 51 and 5J; 5E, 5F, 5H, SI and 5J; or 5F, SG 5fI, 51 and 5. In some embodiments, the non-naturally occurring eukaryotic organism, -60comprises five or more exogenous nucleic acids, wherein each of the five or more exogenous nucleic acids encodes a different acetyl-CoA pathway enzyme. [00119] In yet other ernbodirnents, the acetyl-CoA pathway comprises: 5A, 5B, SC, 5D, SE and 5F; 5A, 5B, 5C, 5D, 5E and 5G; 5A, 5B, 5C, 5D, 5E and 5H; 5A, 5B, 5C, 5D, 5E and 51; 5A, 5B, SC, 5D, 5E and 5J; 5A, 5B, 5C, 5D, 5F and 5G; 5A, 5B, 5C, 5D, 5F and 5H; 5A, 5B, 5C. 5D, 5F and 5I; 5A, 5B, 5C, 5D, 5F and 5H; 5A, 5B, 5C, 5D, 5G and 5H; 5A, 5B, 5C, 5D, 5G and 5I; 5A, 5B, 5C, 5D. 5G and 5J; 5A, 5B, 5C, 5D, 5H and 51; 5A, 5B, 5C, 5D, 5H and 5J; 5A, 5B, 5C, 5), 5I and 5i; 5A, 5B, 5C, 5E, 5F and 5C; 5A, 5B, 5C, 5E, 5F and 5-; 5A, 5B, 5C, 5E, 5F and 5I; SA, 5B, 5C. 5E, 5F and 5J; 5A, 5B, 5C, 5E, 5G and 5H; 5A, 5B, 5C, 5E, 5G and 5I; 5A, 5B, 5C, 5E, 5G and 5J; 5A, 5B, 5C, 5E, 5H- and 5I; 5A, 5B, 5C, SE, F15 and 5J; 5A, 5B, 5C, SE, 5I and J; 5A, 5B, 5C, 5F, 5G and SH; 5A, 5B. 5C, 5F, 5G and 5I; 5A, SB, 5C, 5F, 5G and 5J; 5A, 5B, 5C, 5F, 511 and 51; 5A, 5B, SC, 5F, 5H] and 5i; 5A, 5B, SC, 5F, 51 and 5J; 5A, 5B, 5C, 5G, 5H and 5; 5A, 5B, 5C, 5G, 5H and 5i; 5A, 5B, 5C, 5G, 51 and 5J; 5A, 5B, 5C, 5H, 51 and 5J; SA, 5B, 5D, 5E, and SI; 5A, SB, 5D, 5E, 5-I and 5J; 5A, 5B, 5D, 5E, 51 and 5J; 5A, 5B, 5D, 5F, 5G and 5H; 5A, 5B, 5D, 5F, 5G and 5I; 5A, 5B, 5D, 5F, 5G and 5i; 5A, 5B, 5D, 5F, 5H and SI; 5A, 5B, 5D, 5F, 5H and SJ; 5A, 5B, SD, 5F, 5I and 5J; 5A, 5B, SD, 5G, 5H and 5I; SA, 5B, 5D, 5G, 5H1 and 5i; 5A, 5B, 5D, 5C, 51 and 5i; 5A, 5B, 5), 5H, SI and 5J; 5A, 5B, 5E, 5F, 5G and 5H; 5A, SB, 5E, 5F, 5G and SI; 5A, 5B. 5E, 5F, 5G and SJ; 5A, 5B, 5E, 5F, SH and 5I; 5A, 5B, 5E, 5F, 5-1 and 5; 5A, 5B, 5E, 5F, 5I and 5J; 5A, 5B, 5E, 5G, 5H and 5I; 5A, 5B, 5E, 5G, 5H and 5J; 5A, 5B, 5E, 5G, 5 and 5J; 5A, 5B, 5E, 5H, 5I and 5i; 5A, 5B, 5F, 5G, 5H and SI; 5A, 5B, 5F, 5G, 5H] and 5J; 5A, 5B, 5F, 5G, 51 and 5J; 5A, 5B, 5F, 5Hi, 51 and 5J; 5A, 5B, 5G, 5H, 51 and 5J; 5A, 5C, 5D, 5E, 5F and 5G; 5A, 5C, 5D, 5E, SF and 5H; 5A,5C, 5D, 5E, 5F and 51; SA, 5C, 5D, SE, 5F and 5J; 5A, 5C, SD, 5E, 5G and 5N; 5A, 5C, 5D, 5E, 5G and 51; 5A, 5C, 5D, 5E, 5G and 5J; 5A, 5C, 5), 5E, 5-1 and 51; 5A, 5C, 5D, SE, 5H and 5J; 5A, 5C, 5D, SE, 5I and SJ; 5A, 5C, 5D, 5F, 5G and 5H; 5A, 5C, 5D, 5F, G and 5I; 5A, 5C, 5D, 5F, G and 5J; 5A, 5C, 5D, 5F, 5F1 and 5I; 5A, 5C, SD, 5F, 5H and 5J; 5A, SC, 5D, 5F, 5I and 5J; 5A, 5C, 5D, 5G, H and SI; 5A, 5C, 5D, 5G, H and 5J; SA, 5C, 5D, 5G, SI and 5J; 5A, 5C, SD, 5H, 5I and 5J; SA, SC, 5E, 5F, 5G and 51; 5A, 5C, 5E, 5F, SG and 5I; 5A, SC, 5E, 5F, 5G and 5i; 5A, 5C, 5E, 5F, 5H and 51; 5A, 5C, 5E, 5F, 5H and 5J; 5A, 5C, 5E, 5F, 5I and 5J; 5A, 5C, 5E, 5G, 5N and SI; 5A, 5C, 5E, 5G, 5H and 5J; 5A, SC, 5E, 5G, 51 and 5J; 5A, 5C, 5E, 5H, 5I and 5; -61- 5A, SC, 5F, 5G, 5H and 5I; 5A, 5C, 5F, SG, 5H and 5J; 5A, 5C, 5F, 5G, 5I and 5J; 5A, 5C, 5F, SBH, 51 and 5J; SA, 5C, 5G, 51-1, 51 and 5J; SA, 5D, 5E, 5F, 5G and S1; SA, 5D, 5E, 5F, 5G and 5; 5A, 5D, 5E, 5F, 5G and 5J; 5A, 5D, 5E, 5F, 5H and 5I; 5A, 5D, 5E, 5F, 5H and 5J; 5A, 5D, 5E, 5F, 51 and Si; 5A, 5D, 5E, 5G, 5H and 51; 5A, 5D, SE, SG, 5H and 5J; 5A, 5D, SE, SG, 5I and 5J; 5A, 5D, 5E, 5H 5I and 5i; 5A, 5D, SF, 5G, 5H and 5I; 5A, 5D, 5F, 5G, 5H and 5i; 5A, 5D, SF 5G, 51 and 5; 5A, D, 5F, SH, 5I and 5J; SA 5D, 5G, 511, 51 and 5J; 5A, 5E, 5F, SG SH and 5; 5A, SE, 5F, 5G, 5 and 5J; 5A, 5E, 5F, 5G, 51 and 5J; 5A, 5E, 5F, 5H, 51 and 5i; 5A, 5E, 5G, 5H, 5I and 5J; 5A, 5F, SG, 5H, 5I and 5J; 5B, 5C, 5D, 5E, 5F and 5G; 5B, 5C, SD, 5E, SF and 5H; 5B, 5C, 5D, 5E, 5F and 5I; 5B, 5C, 5D, 5E, SF and 5; 5B, 5C, 5D, 5F, 5G and 5N; 5B, 5C, SD, 5E, 5G and 5I; 5B, 5C, SD, 5E, 5G and 5J; 5B, 5C, 5D, 5E, 5H and 5I; 5B, 5C, 5D, SIE, 5H[ and 51; 51B, 5C, 5D, SIE, 51 and 5; 5B, SC, SD, 5F, 5G and 5 ; 5B, 5C 5D, 5F, 5G and 5; 5B, 5C, 5D, 5F, 5G and 5i; 5B, 5C, 5D, 5F, 5H and 5I; 5B, 5C, 5D, 5F, 5H and 5J; 5B, 5C, 5D, 5F, 51 and 5J; 5B, SC, 5D, 5G, 5H and 5I; 5B, 5C, SD, SC, 5I- and 5J; 5B, 5C, SD, 5G, 5I and 5J; 5B, 5C, 5D, 5H., 5I and 5J; 5B, 5C, 5E, 5F, 5G and 5H; 5B, 5C, 5E, 5F, 5G and 5; 5B, 5C, 5E, 5F, 5G and 5J; 5B, 5C, SE, 5F, 5H and 5I; SB, 5C, SE, 5F. 5H and 5J; 5B, SC, 5E, 5F, 51 and 5i; 5B, 5C, 5E, 5G, 5H and 51; 5B, 5C, 5E, 5G, 5H and 5i; 5B, 5C, 5E, SG, 5I and 5J; 5B, 5C, 5E, 511, 51 and 5J; 5B, 5C, SF, 5G, 5H and 5I; 5B, 5C, 5F, 5G, 5H and 5J; 5B, 5C, 5F, 5G, 5I and 5J; , 5, F, 15H, 51 and 5i; 5B, 5C, 5G, 5H, 51 and 5J; 513, 51), 5E, 5F, 5G and 5H; 5B, 5D, 5E, 5F, 5G and 5I; 5B, 5D, 5E, 5F, 5G and 5J; 5B, 5D, 5E, SF, 5H and 5I; 5B, 5D, 5E, 5F, 5H and 5J; 5B, 5D, 5E, 5F, SI and 5J; 5B, 5D, 5E, 5G, 5H and SI; 5B, 5D, 5E, 5G, 5-I and 5J; 5B, 5D, 5E, 5G, SI and 5J; 5B, 5D, 5E, 5H, 5I and 5i; 5B, 5D, 5F, 5G, 5H and 5; 5B, 5D, 5F, 5G, 5-1 and 5J; 5B, 5D, 5F, 5G, SI and 5J; 5B, 5D, 5F, SN, 5I and 5J; 5B, 5E, 5F, 5G, 5H and 5I; 5B, 5E, 5F, 5G, 5H and 5J; 5B, 5E, 5F, 5G, 51 and 5J; 5B, 5E, 5F, 5H, 5I and 5i; 5B, 5E, 5G, 5H, 51 and 5J; 5B, 5F, 5G, 5H, 5I and 5J; SC, 5D, 5E, 5F, 5H and 5I; 5C, 5D, 5E, 5F, 5H and 5J; 5C, 5D, 5E, 5F, SI and 5J; 5C, 5D, 5E, 5G, 5H and SI; 5C, 5D, 5E, 5G, 5H and 5i; 5C, 5D, 5E, 5G, 5I and 5J; 5C, 5D, SE, 5H, 5I and 5J; SC, 5D, 5F, 5G, 5H and 5I; SC, 5D, 5F, 5G, 5H and 5i; 5C, 5), 5F, 5C, 51 and 5J; 5C, 5), 5F, 5[H, 51 and 5J; 5C, 5D, 5G, 5[, 51 and 5J; 5), 5E, 5F, 5G, 5H and 51; 5D, 5E, 5F, 5G, 5H and 5i; 5D, 5E, 5F, 5G, 5 and 5J; 5D, 5E, 5F, 5H, 5I and 5J; 5D, SE, 5G, 5N, 5I and 5J; or 5E, 5F,5G, 511, SI and 5J. In some embodiments, the non naturally occurring eukaryotic organism, comprises six or more exogenous nucleic acids, -62wherein each of the six or more exogenous nucleic acids encodes a different acetyl-CoA pathway enzyme. [00120] In some embodiments, the acetyl-CoA pathway comprises: SA, 5B, SC, 5D, 5E, 5F and 5G; 5A, 5B, 5C, 5D, 5E, 5F and 5H; 5A, 5B, 5C, 5D, 5E, 5F and 5I; 5A, 5B, 5C, 5D, SE, 5F and 5J; 5A, 5B, 5C, 5D, 5E, 5G and 51-1; 5A, 5B, 5C, SD, 5E, 5G and 51; 5A, 5B, 5C, 5D, 5E, 5G and 5J; 5A, 5B, 5C, 5D, 5E, 5H and 5I; 5A, B, 5C, 5D, 5E, 5H and 5J; 5A, 5B, 5C, 5D, 5E, 5I and 5J; 5A, 5B, 5C, 5D, 5F, 5G and 5H; 5A, 5B, 5C, 5D, 5F, 5G and 51; 5A, 5B, SC, 5D, 5F, 5G and 5i; 5A, 5B, 5C, 5D, 5F, 5FH and 5I; 5A, 5B, 5C, 5D, 5F, 5H and 5i; 5A, 5B, 5C, 5D, 5F, 51 and 5J; 5A, SB, 5C, 5D, 5F, 5H and SI; 5A, 5B, 5C, 5D, SF, 5H and 5J; 5A, 5B, 5C, 5D. 5G, 5H and SI; 5A, SB, 5C, 5D, 5G, 51 and 5i; 5A, 5B, 5C, 5D, 5G, 5I and 5i; 5A, 5B, 5C, 5D, 5-, 51 and 5J; 5A, 5B, 5C, 5E, 5F, SG and 5H; 5A, 5B, SC, 5E, 5F, 5G and SI; 5A, 5B. 5C, SE, 5F, 5G and 5; 5A, 5B, SC, 5E, 5F, 51H and 51; 5A, 5B, 5C, SE, 5F, 5H and 5J; 5A, 5B, 5C, SE, 5F, 5I and 5J; 5A, 5B, 5C, 5E, 5G, 5H and 5I; 5A, 5B, 5C, 5E, 5G, 5H and 5J; 5A, 5B, 5C, 5E, 5G, 5I and 5J; 5A, 5B, 5C, 5E, SH, 5I and 5J; SA, 5B, SC, 5F, 5G, 5H] and 5I; 5A, 5B, 5C, 5F, 5G, 511 and 5J; 5A, 5B, 5C, 5F, 5G, 51 and 5J; 5A, 5B, 5C, 5F, 5H, 5I and 5i; 5A, 5B, 5C, 5G, 5H, 5I and 5J; 5A, 5B, 5D, 5E, 5H, 5I and 5J; 5A, 5B, 5D. 5F, 5G, 5H and 5I; 5A, 5B. 5D, 5F, 5G, 5H and 51; 5A, 5B, 5D, 5F, 5G, 51 and 5J; 5A, 5B, 5D, SF, 51, 5I and 5i; 5A, 5B, 5D, 5G, 5H, SI and 5J; 5A, SB, 5E, 5F, 5G, SH and 5I; 5A, SB, 5E, 5F, 5G, SH and 5J; 5A, 5B, 5E, 5F. 5G., SI and 5J; 5A, 5B, 5E, 5F, 511, 5I and 5J; 5A, 5B, 5E, 5G, 511, 51 and 5J; 5A, 5B, 5F, 5G, 5H, SI and 5J; 5A, 5C, 5D, 5E, 5F, 5G and 5H; 5A, 5C, 5D, 5E, 5F, 5G and 5I; 5A, 5C, 5D, 5E, 5F, 5G and Si' 5A, 5C, SD, 5E, 5F, 511 and 51; 5A, 5C, SD, 5E, 5F, 511 and 5J; 5A, SC, 5D, 5E, 5F, SI and 5i; 5A, 5C, 5D, 5E, 5G, 5H and 5I; 5A, 5C, 5D, 5E, 5G, 5H and 5J; 5A, 5C, 5D, 5E, 5G, 51 and 5J; SA, SC, 5D, 5E, 5H, SI and 5J; 5A, SC, 5D, 5F, SG, 5H and 51; SA, 5C, 5D, 5F, 5G, 511 and 5J; 5A, 5C, 5D, 5F, 5G, 5I and 5i; 5A, 5C, 5), 5F, 5-, 51 and 5J; 5A, 5C, 5D, 5G, 51-1,51 and 5J; 5A, 5C, 5E, SF, 5G, 5H and 5I; 5A, 5C, 5E, 5F, 5G, 5H and 'J 5A, 5C, 5E, 5F, 5G, 5I and 51; 5A, SC, 5E, 5F, 5F1, 51 and 5i; 5A, 5C, 5E, 5G, 5H, 51 and 5i; 5A, 5C, 5F, 5G, 5-i, 51 and 5J; 5A, SD, 5E, 5F, 5G, 5H and SI; 5A, 5D, SE, 5F, 5G 5H and 5J; 5A, 5D, 5E, 5F. 5G, 5I and 5J; SA, SD, 5E, 5F, 5-I, 51 and 5J; 5A, 5D, SE, 5GH,5F, 5I and 5i; SA, 5D, 5F, SG, 5H, 51 and 5J; 5A, 5E, 5F, 5G, 5H, 51 and 5J; 5B, 5C, 5D, 5E, 5F, 5G and 5H; 5B, 5C, 5D, 5E, 5F, 5G and SI; 5B, 5C, 5D, SE, 5F, 5G and 5J; 5B, 5C, 5D, SE, 5F, 5H and 5I; SB, 5C, SD, 5E, 5F, 5ri -63 and 5J; 5B, 5C, 5D, 5E, 5F, 5I and 5J; 5B, 5C, 5D, 5E, 5G, 5H and 5I; 5B, 5C, 5D, 5E, 5G, 5H and 5i; SB, 5C, 5D, 5E, S, 51 and 5J; 5B, 5C, SD, 5E, 51, 5I and 5i; 513, 5C, 5D, 5F, 5G, 5H and 5I; 5B, 5C, 5D, 5F, 5G, 5H and 5J; 5B, 5C, 5D, 5F, 5G, 51 and 5J; 5B, 5C, 5D, 5F, 5H, 51 and 5J; SB, 5C, 5D, 5G, 5H, 51 and 5J; 5B, 5C, 5E, 5F, 5G, 5H and 5I; 5B, 5C, 5E, 5F, 5G, 5H and 5J; 5B, 5C, 5E, 5F, 5G, 51 and 5J; 5B, 5C, 5E, 5F, 5H, 51 and 5J; 5B, 5C, 5E, 5G, 5H, 5I and 5J; 5B, 5C, 5F, 5G, 5H, 51 and 5J; 5B, 5D, 5E, 5F, 5G, 511 and 51; 5B, 5D, 5E, 5F, 5G, 511 and 5J; 5B, 5D, SE, 5F, 5G, 5I and 5J; 5B, 5D, SE, 5F, 5H1, 5I and 5i; 5B, 5D, SE, 5G, 51-1, 5I and 5J; SB, SD, SF, 5G, SH, SI and SJ; SB, SE, SF, 5G, 5H, 5I and 5J; 5C, 5D. SE. SF, 5H, 5I and 5J; 5C, 5), 5[, 5G, 51-1, 51 and 5J; 5C, 5), 5F, 5G, 51, 5I and 5J; or 5), 5E, 5F, 5G, 51, 5I and 5J. In some embodiments, the non-naturally occurring eukaryotic organism, comprises seven or more exogenous nucleic acids, wherein each of the seven or more exogenous nucleic acids encodes a different acetyl-CoA pathway enzyme. [001211 In certain embodiments, the acetyl-CoA pathway comprises: 5A, 5B, 5C, 5D, 5E., 5F, 5G and 5H; 5A, SB, 5C, 5D, 5E, 5F, 5G and 51; 5A, 5B, 5C, 5D, 5E, 5F, 5G and 5; 5A, 5B, 5C, 5D, 5E, 5F, 5H and 51; 5A, 5B, 5C, 5D, 5E, 5F, 5H and 5J; 5A, 5B, 5C, 5D, 5E, 5F, 5I and 5J; 5A, 5B, 5C, 5D, 5E, 5G, 5H and SI; N5A 5B, 5C, 5D, 5E, 5G, 5H and 5J; 5A, 5B, 5C, 5D, 5E, 5, 51 and 5J; SA, 513, 5C, 5D, 5E, 5H, 51 and 5i;15A, 5B, 5C, SD, 5F, 5, 5H and 51; 5A, 5B, 5C, 5D, 5F. 5G, 5H and J; 5A, 5B, 5C, 5D, 5F, 5G. 51 and J; 5A, 5B, 5C, 5D, 5F, 5H, 51 and 5i; 5A, 5B, 5C, 5D, 5F, 5H, 5I and 5i; 5A, 5B, 5C, 5D, 5G, 5H, 51 and 5i; 5A, 5B, 5C, 5E, 5F, 5G, 51H and 51; 5A, 5B, 5C, 5E, 5F, 5G, 5H and 5J; 5A, 5B, 5C, 5E, 5F, 5G, 51 and 5J; 5A, 5B. 5C, 5E, 5F, 511, 51 and 5J; 5A, SB, 5C, 5E, 5G, 5H, 5I and 5J; 5A, 5B, 5C, 5F, 5G, 5, 5I and 5J; 5A, 5B, 5D, 5F, 5G, 5H, 51 and 5J; 5A, 5B, 5E, 5F, 5G, 5H, 51 and 5J; 5A, 5C, 5D, 5E, 5F, 5G, 5ri and 5; 5A, 5C, 5D, 5E, 5F, 5G, 511 and 5J; 5A, 5C, 5D, 5E, 5F, 5G, 51 and 5i; 5A, 5C, 5), 5E, 5F, Sri, 51 and 5J; 5A, 5C, 5D, 5E, 5 SFH, 5I and 5i; 5A, 5CF,SD,51, 5G, 5H, 51 and J; 5A, 5C, 5E, 5F, 5G, 5H, 51 and 5J; 5A, 5D, 5E, 5F, 5G, 5H, 51 and 5J; 5B, 5C, 5D, 5E, 5F, SG, 5 and 5I; 5B, 5C, 5), 5E, 5F, 5G, 5H1- and 5J; 513, 5C, 5D, 5E, 5F, 5G, 51 and 5J; 5B, 5C, 5D, 5E, 5F, 5H, SI and 5J; 5B, 5C, 5D, SE, 5G, 5H, 51 and 5J; 5B, 5C, 5D, 5F, 5G, 511, 51 and 5J; 5B, 5C, 5E, 5F, 5G, 5H, 5I and 5J; or 5B, 5D, 5E, 5F, 5G, 511, 51 and 5J. In sonie embodiments, the non-naturally occurring eukaryotic organism, comprises eight or more -64exogenous nucleic acids, wherein each of the eight or more exogenous nucleic acids encodes a different acetyl-CoA pathway enzyme. [00122] In some embodiments, the acetyl-CoA pathway comprises 5A, 5B, 5C, 5D, 5E, 5F, 5G, 5H and 5I; 5A, 5B, 5C, 5D, 5E, 5F, 5G, 5H and 5J; 5A, 5B,5C, 5D, 5ESF, 5G, 5I and 5J; 5A, 5B, 5C, 5D, 5E, 5F, 5H, 5I and 5J; 5A, 513, 5C, 5D, 5E, 5G, 5H, 51 and 5J; 5A, 5B, 5C, 5D, 5F, 5G, 5H, 5I and 5J; 5A, 5B, 5C, 5E, 5F, 5G, 5H, 51 and 5J; 5A, 5C, SD, 5E, 5F, 5, SH, SI and 5J; or 5B, 5C, D, 5E, 5F, 5G. 5H, 5I and 5J. In some embodiments, the non-naturally occurring eukaryotic organism, comprises nine or more exogenous nucleic acids, wherein each of the nine or more exogenous nucleic acids encodes a different acetyl-CoA pathway enzyme. [001231 In other embodiments, the acetyl-CoA pathway comprises -A, SB, 5C, 5D, 5E, SF, 5C, 5-1, 51 and SJ. In some embodiments, the non-naturally occurring eukaryotic organism, comprises ten or more exogenous nucleic acids, wherein each of the ten or more exogenous nucleic acids encodes a different acetyi-CoA pathway enzyme. [00124] In certain embodiments, the acetyl-CoA pathway comprises 6A, 613, 6C, 6D or 6E, or any combination of 6A, 6B, 6C, 6D and 6E thereof, wherein 6A is mitochondrial acetvlcarnitine transferase; 6B is a peroxisomal acetylcamitine transferase; 6C is a cytosolic acetylcarnitine transferase; 61) is a mitochondrial acetylcarnitine translocase; and 6E. is peroxisonal acetylcamitine translocase. [001251 In some embodiments, the acetyl-CoA pathway is an acetyl-CoA pathway depicted in FIG. 6. In a specific embodiment, the acetyl-CoA pathway comprises 6A, 6D and 6C. In another specific embodiment, the acetyl-CoA pathway comprises 6B, 6E and 6C. [00126] In one embodiment, the acetyl-CoA pathway comprises 6A. In another embodiment, the acetyl-CoA pathway comprises 6B. In some embodiments, the 6C. In other embodiments, 61), In yet other embodiments, 6E. In some embodiments, the non-naturally occurring eukaryotic organism, comprises one or more exogenous nucleic acids, wherein each of the one or more exogenous nucleic acids encodes a different acetyl-CoA pathway enzyme. -65- [001271 In some embodiments, the acetyl-CoA pathway comprises: 6A and 613; 6A and 6C; 6A and 61); 6A and 6E; 613 and 6C; 613 and 61D; 613 and 6E; 6C and 613; 6C and 6E.; or 61) and 6E. In some embodiments, the non-naturally occurring eukaryotic organism comprises two or more exogenous nucleic acids, wherein each of the two or more exogenous nucleic acids encodes a different acetyl-CoA pathway enzyme. 1001281 In other embodiments, the acetyl-CoA pathway comprises: 6A, 6B and 6C; 6A, 6B and 6D; 6A, 6B and 6E; 6A, 6C and 6D; 6A, 6C and 6E; 6A. 6D and 6E; 6B, 6C and 6D; 613, 6C and 6E; or 6C, 6D and 6E. In some embodiments, the non-naturally occurring eukaryotic organism, comprises three or more exogenous nucleic acids, wherein each of the three or more exogenous nucleic acids encodes a different acetyl-CoA pathway enzyme. 1001291 In another embodiment, the acetyl-CoA pathway comprises: 6A, 613, 6C and 61); 6A, 6B, 6C and 6E; or 613, 6C, 6D and 6E. In some embodiments, the non-naturally occurring eukaryotic organism. comprises four or more exogenous nucleic acids, wherein each of the fbur or more exogenous nucleic acids encodes a different acetyl-CoA pathway enzyme. [001301 In yet another embodiment, the acetyl-CoA pathway comprises 6A, 6B, 6C, 6D and 6E. In some embodiments, the non-naturally occurring eukaryotic organism, comprises five or more exogenous nucleic acids, wherein each of the five or more exogenous nucleic acids encodes a different acetyl-CoA pathway enzyme. [001311 In some embodiments, the acetyl-CoA pathway comprises 1OA, 10B, 1OC, IOD, 10F, 10G, 1011. 10J, 10K, 10L, 10M, ION, or any combination of 10A, 1013, 10C, 10D, 10, 10G, 1OH. 1OJ, I OK, IOL, 10M 1 ON' thereof wherein 1OA is a PEP3 carboxylase or PEP carboxykinase; 10B is an oxaloacetate decarboxylase; 10C is a malonate semialdehyde dehydrogenase (acetylating); 10D is a malonyl-CoA decarboxylase; 1OF is an oxaloacetate dehydrogenase or oxaloacetate oxidoreductase; lOG is a malonyl-CoA reductase; 1OH is a pyruvate carboxylase; 10. is a malonate semialdehyde dehydrogenase; 1 OK is a malonyl-CoA synthetase or transferase; 1OL is a malic enzyme; 1OM is a malate dehydrogenase or oxidoreductase; and ION is a pyruvate kinase or PIEP phosphatase. In one embodiment, 10A is a PEP carboxylase. In another embodiment, bOA is a PEP carboxykinase. In an embodiment, I OF -66is an oxaloacetate dehydrogenase. In other embodiments. IOF is an oxaloacetate oxidoreductase. In one embodiment, 10K is a malonyl-CoA synthetase. In another embodiment, 10K is a malonyl-CoA transferase. In one embodiment, 1DM is a malate dehydrogenase. In another embodiment, 10M is a malate oxidoreductase. In other embodiments, ION is a pyruvate kinase. In some embodiments, ION is a PEP phosphatase. 1001321 In one embodiment, the acetyl-CoA pathway comprises I0A. In some embodiments, the acetyl-CoA pathway comprises 1DB. In other embodiments, the acetyl-CoA pathway comprises I 0C. In another embodiment, the acetyl-CoA pathway comprises 10D. In some embodiments, the acetyl-CoA pathway comprises 1OF. In one embodiment, the acetyl-CoA pathway comprises 1OG. In other embodiments, the acetyl-CoA pathway comprises 101-I. In yet other embodiments, the acetyl-CoA pathway comprises 1 OJ. In some embodiments, the acetyl CoA pathway comprises 10K. In certain embodiments, the acetyl-CoA pathway comprises 10L In other embodiments, the acetyl-CoA pathway comprises 1DM. In another embodiment, the acetyl-CoA pathway comprises ION. [001331 In some embodiments, the acetyl-CoA pathway further comprises 7A, 7E or 7F, or any combination of 7A, 7E and 7F thereof, wherein 7A is an acetoacetyl-CoA thiolase ([1G. 10, step I), 7E is an acetyl-CoA carboxylase (FIG. 10, step D); and 7F is an acetoacetyl-CoA synthase (F 1 i. 10, step E). [001341 In some embodiments, the acetyl-CoA pathway is an acetyl-CoA pathway depicted in FIG. 10. In a specific embodiment, the acetyl-CoA pathway comprises IDA, IOB and I0C. In some embodiments, the acetyl-CoA pathway comprises ION, 10, JOB and 10C. In other embodiments, the acetyl-CoA pathway comprises ION, IOL, 1DM, lOB and 10C. In another embodiment, the acetyl-CoA pathway comprises iA, lOB, 1OG and 1OD. In some embodiments, the acetVl-CoA pathway comprises ION, 10H, 1013, 1OG and 10D. In one embodiment, the acetyl-CoA pathway comprises IDN, IOL, 1DM, 1OB, lOG and 1OD. In other embodiments, the acetyl-CoA pathway comprises I0A, 10B3, 10J, 10K and 101). In yet other embodiments, the acetyl-CoA pathway comprises ION, IOH, 1DB, I0J, IDK and 1OD. In some embodiments, the acetyl-CoA pathway comprises ION, 10 L, 10M, 10 B, 10J, IOK and IOD. In certain embodiments, the acetyl-CoA pathway comprises I GA, 1 OF and I OD. In other -67embodiments, the acetyl-CoA pathway comprises ION, I0H, IOF and 1OD. In another embodiment, the acetyl-CoA pathway comprises ION, 10L, 1 OM, I OF and 10). [00135] While generally described herein as a eukaryotic organism that contains an acetyl CoA pathway, it is understood that also provided herein is a non-naturally occurring eukaryotic organism comprising at least one exogenous nucleic acid encoding an acetyl-CoA pathway enzyme expressed in a sufficient amount to produce an intermediate of an acetyl-CoA pathway. For example, as disclosed herein, an acetyl-CoA pathway is exemplified in FIGS. 2, 3, 5. 6, 7,8 and 10. Therefore, in addition to a eukaryotic organism containing an acetyl-CoA pathway that is capable of producing cytosolic acetyl-CoA in said organism. transporting acetyl-CoA from a mitochondrion or peroxisome of said organism to the cytosol of said organism and/or increasing acetyl-CoA in the cytosol of said organism, also provided herein is a non-naturally occurring eukaryotic organism comprising at least one exogenous nucleic acid encoding an acetyl-CoA pathway enzyme, where the eukaryotic organism produces an acetyl-CoA pathway intermediate, for example, citrate, citramalate, oxaloacetate, acetate, malate, acetaldehyde, acetylphosphate or acetylcarnitine. 1001361 It is understood that any of the pathways disclosed herein, as described in the Examples and exemplified in the figures, including the pathways of FIGS. 2, 3, 4, 5, 6, 7, 8 9 or 10, can be utilized to generate a non-naturally occurring eukaryotic organism that produces any pathway intermediate or product, as desired. As disclosed herein, such a eukaryotic organism that produces an intermediate can be used in combination with another eukaryotic organism expressing downstream pathway enzymes to produce a desired product. However, it is understood that a non-naturally occurring eukaryotic organism that produces an acetyl-CoA pathway intermediate can be utilized to produce the intermediate as a desired product. [001371 Any non-naturally occurring eukaryotic organism comprising an acetyl-CoA pathway and engineered to comprise an acetyl-CoA pathway enzyme, such as those provided herein, can be engineered to further comprise one or more 1,3-13DO pathway enzymes. In some embodiments, the non-naturally occurring eukaryotic organisms having a 1,3-BDO pathway include a set of 1,3-BDO pathway enzymes. A set of I,3-BDO pathway enzymes represents a group of enzymes that can convert acetyl-CoA to 1,3-BDO, e.g., as shown in FIG. 4 or FIG. 7. -68- [001381 In some embodiments, provided herein is a non-naturally occurring eukaryotic organism, comprising (1) an acetyl-CoA pathway, wherein said organism comprises at least one exogenous nucleic acid encoding an acetyl-CoA pathway enzyme expressed in a sufficient amount to (i) transport acetyl-CoA from a mitochondrion and/or peroxisome of said organism to the cytosol of said organism, (ii) produce acetyl-CoA in the cytoplasm of said organism, and/or (iii) increase acetyl-CoA in the cytosol of said organism; and (2) a 1,3-BDO pathway, comprising at least one exogenous nucleic acid encoding a 1,3-13DO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO. In one embodiment, the at least one acetyl-CoA pathway enzyme expressed in a sufficient amount to transport acetyl-CoA from a mitochondrion and/or peroxisome of said organism to the cytosol of the organism. In one embodiment, the at least one acetyl-CoA pathway enzyme is expressed in a sufficient amount to produce cytosolic acetyl-CoA in said organism. In another embodiment, the at least one acetyl-CoA pathway enzyme is expressed in a sufficient aniount to increase acetyl-CoA in the cytosol of said organism. In some embodiments, the acetyl CoA pathway comprises any of the various combinations of acetyl-CoA pathway enzymes described above or elsewhere herein. In certain embodiments, 1,3-BDO byproduct pathways are deleted. [001391 In certain embodiments, (1) the acetyl-CoA pathway comprises: 2A, 213, 2C, 21), 2E, 2F, 2G, 2K, 2L, 3H, 31 or 3J, or any combination of 2A, 213, 2C 2D, 2E, 2F, 2G, 3H, 3 and 3J, thereof; wherein 2A is a citrate synthase; 213 is a citrate transporter; 2C is a citrate/oxaloacetate transporter or a citrate/malate transporter; 2D is an ATP citrate lyase; 2E is a citrate lyase; 2F is an acetyl-CoA synthetase; 2G is an oxaloacetate transporter; 2K is an acetate kinase; 2L is a phosphotransacetylase; 3H is a cytosolic malate dehydrogenase; 31 is a malate transporter; and 3J is a mitochondrial palate dehydrogenase; and (2) the 1,3-BDO pathway comprises 4A, 4B, 4C, 41), 4E, 4F, 4G, 41], 41, 4J, 4K, 4L, 4M, 4N or 40, or any combination of 4A, 413, 4C, 4D, 4E, 44F, 4G, 4H, 4I, 4J, 4K, 4L, 44M, 4N and 40 thereof; wherein 4A is an acetoacetyl-CoA thiolase; wherein 413 is an acetoacetyl-CoA reductase (CoA -dependent, alcohol forming); wherein 4C is a 3-oxobutyraldehyde reductase (aldehyde reducing); wherein 4D is a 4--hydroxy,2-butanone reductase; wherein 4E is an acetoacetyl-CoA reductase (CoA-dependent, aldehyde forming); wherein 4F is a 3-oxobutyraldehyde reductase (ketone reducing); wherein 4G is a 3 hydroxybutyraldehyde reductase; wherein 41 is an acetoacetyl-CoA reductase (ketone -69reducing); wherein 41 is a 3-hydroxybutyryl-CoA reductase (aldehyde fonning); wherein 4J is a 3-hydroxybutyryl-CoA reductase (alcohol forming); wherein 4K is an acetoacetyl-CoA transferase, an acetoacetyl-CoA hydrolase, an acetoacetyl-CoA synthetase, or a phosphotransacetoacetylase and acetoacetate kinase; wherein 4L is an acetoacetate reductase; wherein 4N is a 3-hvdroxybutyrvl-CoA transferase, hydrolase, or synthetase; wherein 4N is a 3 hydroxybutyrate reductase; and wherein 40 is a 3-hydroxybutyrate dehydrogenase. In some embodiments, 2C is a citrate/oxaloacetate transporter. In other embodiments, 2C is a citrate/malate transporter. In certain embodiments, 4K is an acetoacetyl-CoA transferase. In other embodiments, 4K is an acetoacetyl-CoA hydrolase. In some embodiments, 4K is an acetoacetyl-CoA synthetase. In other embodiments, 4K is a phosphotransacetoacetylase and acetoacetate kinase. In certain embodiments, 4M is a 3-hydroxybutyryl-CoA transferase. In some embodiments, 4M is a 3-hydroxybutyryl-CoA, hydrolase. In yet other embodiments, 4M is a 3-hydroxybutyryl-CoA synthetase. [001401 In one embodiment, the 1,3-BDO pathway comprises 4A. In another embodiment, the 1,3-BDO pathway comprises 4B. In an embodiment, the 1,3-BDO pathway comprises 4C. In another embodiment, the 1,3-BDO pathway comprises '4D. In one embodiment, the 1,3-BDO pathway comprises 4E. In yet another embodiment, the 1,3-BDO pathway comprises 4F. In some embodiments, the 1.3-BDO pathway comprises 4G. In other embodiments, the 1,3-BDO pathway comprises 4H. In another embodiment, the 1,3-3DO pathway comprises 41. In one embodiment, the 1,3-BDO pathway comprises 4J. In one embodiment, the 1,3-BDO pathway comprises 4K. In another embodiment, the 1,3-BDO pathway comprises 4L In an embodiment, the 1,3 -BDO pathway comprises 4M. In another embodiment, the 1,3-BDO pathway comprises 4N, In one embodiment, the I ,3-BDO pathway comprises 40. [001411 In some embodiments, the acetyl-CoA pathway is an acetyl-CoA pathway depicted in FIG. 2, and the 1,3-1DO pathway is a 1,3-3DO pathway depicted in FIG. 4. In other embodiments, the acetyl-CoA pathway is an acetyl-CoA pathway depicted in FIG. 3, and the 1,3 BDO pathway is a 1,3-13DO pathway depicted in FIG, 4. In yet other embodiments, the acetyl CoA pathway is an acetyl-CoA pathway depicted in FIG. 7, and the 1,3-BDO pathway is a 1,3 BDO pathway depicted in FIG, 4 or FIG. 7. Exemplary sets of 1,3-BDO pathway enzymes to -70convert acetyl-CoA to 1,3-BDO,. according to FIG. 4, include 4A, 4E, 4F and 4G; 4A, 4B and 4D; 4A, 4E, 4C and 41D; 4A, 411 and 4J; 4A, 4H, 41 and 4G; 4A, 41-1, 4M, 4N and 4G; 4A, 4K, 40, 4N and 4G; or 4A, 4K, 4L, 4F and 4G. [001421 In one embodiment, the acetyl-CoA pathway comprises 2A, 2B and 2D. In another embodiment, the acetyl-CoA pathway comprises 2A, 2C and 2D. In yet another embodiment, the acetyl-CoA pathway comprises 2A, 2B, 2C and 2D. In an embodiment, the acetyl-CoA pathway comprises 2A 2B, 2E and 2F. In another embodiment, the acetyl-CoA pathway comprises 2A, 2C, 2F and 2F. In other embodiments, the acetyl-CoA pathway comprises 2A, 2B, 2C, 2E and 2F. In some embodiments, the acetyl CoA pathway comprises 2A, 2B, 2E, 2K and 2L In another embodiment, the acetyl CoA pathway comprises 2A, 2C, 2E, 2K and 2L In other embodiments, the acetyl CoA pathway comprises 2A, 2B, 2C 2 1 E, 2K and 2L. In some embodiments, the acetyl-CoA pathway further comprises 2G, 3H, 31, 3J, or any combination thereof In certain embodiments, the acetyl-CoA pathway further comprises 2G. In some embodiments, the acetyl-CoA pathway further comprises 31-1. In other embodiments, the acetyl CoA pathway further comprises 31. In yet other embodiments, the acetyl-CoA pathway further comprises 3J. In some embodiments, the acetyl-CoA pathway further comprises 2G and 3H. In an embodiment, the acetvl-CoA pathway further comprises 2(G and 31. In one embodiment, the acetyl-CoA pathway further comprises 2G and 3J. In some embodiments, the acetyl-CoA pathway further comprises 311 and 31. In other embodiments, the acetyl-CoA pathway further comprises 3H and 3J. In certain embodiments, the acetyl-CoA pathway further comprises 31 and 3J. In another embodiment, the acetyl-CoA pathway further comprises 2G, 31 and 31. In yet another embodiment, the acetyl-CoA pathway further comprises 2G, 31H and 3J. In some embodiments, the acetyl-CoA pathway further comprises 2G, 31 and 3J. In other embodiments, the acetyl-CoA pathway further comprises 3H, 31 and 3J. 1001431 Any of the acetyl-CoA pathway enzymes provided herein can be in combination with any of the 1 ,3-BDO pathway enzymes provided herein. [001441 In one embodiment, the 1.3-BDO pathway comprises 4A., 4E., 4F and 4G. In another embodiment, the 1,3-BDO pathway comprises 4A, 4B and 4D. In other embodiments, the 1,3 BDO pathway comprises 4A, 4E, 4C and 4D. In some embodiments, the 1,3-BDO pathway -71comprises 4A, 4H and 42J. In other embodiments, the 1,3-BDO pathway comprises 4A, 4H, 41 and 4G;. In certain embodiments, the 1,3-3DO pathway comprises 4A, 41-, 41, 4N and 4(i. In another embodiment, the 1,3-BDO pathway comprises 4A, 4K, 40, 4N and 4G. In yet another embodiment, the 1,3-BDO pathway comprises 4A, 4K, 4L, 4F and 4G. [001451 In certain embodiments, (1) the acetyl-CoA pathway comprises (i) 2A 2B and 2D; (ii) 2A, 2C and 2D; (iii) 2A, 2B, 2C and 2D; (iv) 2A, 2B, 2E and 2F; (v) 2A, 2C, 2E and 2F; (vi) 2A, 2B. 2C, 2E and 2F; (vii) 2A, 2B, 2E, 2K and 2L; (viii) 2A, 2C, 2E, 2K and 2L or (ix) 2A, 2B, 2C, 2E, 2K and 2L, and wherein the acetyl-CoA pathway optionally further comprises 2G, 3HI, 31, 3J, or any combination thereof; and (2) the 1,3-BDO pathway comprises (i) 4A, 4E, 4F and 4G; (ii) 4A, 41B and 41); (iii) 4A, 4E, 4C and 41; (iv) 4A, 4H1- and 4J; (v) 4A, 4H, 41 and 4G; (vi) 4A, 4H, 4M. IN and 4G; (vii) 4A, 4K, 40, 4N and 4G; or (viii) 4A, 4K, 4L, 4F and 4G. 1001461 In some embodiments, (I) the acetyl-CoA pathway comprises 2A, 2B and 2D; and (2) the 1,3-BDO pathway comprises (i) 4A, 4E, 4F and 4G; (ii) 4A, 4B and 4D; (iii) 4A, 4E, 4C and 4D; (iv) 4A, 4H and 4J; (v) 4A, 4H, 41 and 4G; (vi) 4A, 4H, 4M, 4N and 4G; (vii) 4A, 4K, 40, 4N and 4G; or (viii) 4A, 4K, 4L, 4F and 4G. In some embodiments, the acetyl-CoA pathway comprises 2A, 213 and 2), and the 1,3-BDO pathway comprises 4A, 41E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises 2A, 2B and 2D, and the 1,3-BDO pathway comprises 4A, 413 and 4D. In one embodiment, the acetyl-CoA pathway comprises 2A, 213 and 2D. and the 1,3-BDO pathway comprises 4A, 4E, 4C and 4D. In some embodiments, the acetyl CoA pathway comprises 2A, 2B and 2D, and the 1,3-BDO pathway comprises 4A, 4H and 4J. In other embodiments, the acetyl-CoA pathway comprises 2A, 2B and 2D, and the 1,3-BDO pathway comprises 4A, 4H, 41 and 4G. In certain embodiments, the acetyl-CoA pathway comprises 2A, 2B and 2D, and the I,3-BDO pathway comprises 4A, 4H, 4M, 4N and 4G. In another embodiment, the acetyl-CoA pathway comprises 2A, 2B and 2D. and the 1,3-BDO pathway comprises 4A, 4K, 40, 4N and 4G. In yet another embodiment, the acetyl-CoA pathway comprises 2A 2B and 2D, and the 1,3-BDO pathway comprises 4A, 4K, IL., 4F and 4G. In certain embodiments, the acetyl-CoA pathway optionally further comprises 2G, 31-1, 31, 3J, or any combination thereof. In some embodiments, the non-naturally occurring eukaryotic -72organism comprises exogenous nucleic acids, wherein each of the exogenous nucleic acids encodes a different acetyl-CoA pathway or 1,3-3DO pathway enzyme. [00147] In other embodiments, (1) the acetyl-CoA pathway comprises 2A, 2C and 2D; and (2) the 1,3-BDO pathway comprises (i) 4A, 4E, 4F and 4G; (ii) 4A, 4B and 4D; (iii) 4A, 4E, 4C and 4D; (iv) 4A, 41] and 4J; (v) 4A, 4H, 41 and 4G; (vi) 4A, 4H, 4M, 4N and 4G; (vii) 4A, 4K, 40, 4N and 4G; or (viii) 4A, 4K, 4L, 4F and 4G. In some embodiments, the acetyl-CoA pathway comprises 2A, 2C and 2D, and the I,3-BDO pathway comprises 4A, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises 2A, 2C and 2D, and the I,3-BDO pathway comprises 4A, 4B and 4D. In one embodiment, the acetyl-CoA pathway comprises 2A, 2C and 2D, and the 1,3-3DO pathway comprises 4A, 4E, 4C and 4D. In some embodiments, the acetyl CoA pathway comprises 2A, 2C and 2D, and the 1,3-BDO pathway comprises 4A, 4H and 4J. In other embodiments, the acetyl-Co A pathway comprises 2A, 2C ard 2D, and the 1,3-BDO pathway comprises 4k, 4H, 41 and 4G. In certain embodiments, the acetyl-CoA pathway comprises 2A, 2C and 2D, and the 1,3-BDO pathway comprises 4A, 411, 4M, 4N and 4G. In another embodiment, the acetyl-CoA pathway comprises 2A, 20 and 2D, and the 1,3-BDO pathway comprises 4A, 4K, 40, 4N and 4G. In yet another embodiment, the acetyl-CoA pathway comprises 2 A, 2C and 21), and the 1,3-BDO pathway comprises 4A, 4K, 4L, 4F and 4G. In certain embodiments, the acetyl-CoA pathway optionally further comprises 2G, 3H, 31, 33, or any combination thereof. In some embodiments, the non-naturally occcurrinng eukaryotic organism comprises exogenous nucleic acids, wherein each of the exogenous nucleic acids encodes a different acetyl-CoA pathway or 1,3-BDO pathway enzyme. [00148] In other embodiments, (1) the acetyl-CoA pathway comprises 2A, 213, 2C and 2D; and (2) the 1,3-BDO pathway comprises (i) 4A, 4E, 4F and 4G; (ii) 4A, 4B and 4D; (iii) 4k, 4E, 4C and 4-D; (iv) 4A, 41H and IJ (v) 4A, 4H, 41 and 4G; (vi) 4A, 4H, 4M, 4N and 4G; (vii) 4A, 4K, 40, 4N and 4G; or (viii) 4A, 4K, 4L, 4F and 4G. In some embodiments, the acetyl-CoA pathway comprises 2A, 21B, 2C and 2D, and the 1,3-BDO pathway comprises 4A, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises 2A, 2B, 2C and 21), and the 1,3 BDO pathway comprises 4A, 4B and 4D. In one embodiment, the acetyl-CoA pathway comprises 2A, 213, 2C and 2D, and the 1,3-BDO pathway comprises 4A, 4E, 4C and 4D. In -73 some embodiments, the acetyl-CoA pathway comprises 2A, 2B, 2C and 2D, and the 1,3-BDO pathway comprises 4A, 4H and 4J. In other embodiments, the acetyl-CoA pathway comprises 2A, 213, 2C and 2D, and the 1,3-BDO pathway comprises 4A, 4H, 41 and 4G. In certain embodiments, the acetyl-CoA pathway comprises 2A, 2B, 2C and 2D, and the 1,3-BDO pathway comprises 4A, 4H, 4M, 4N and 4G. In another embodiment, the acetyl-CoA pathway comprises 2A, 2B, 2C and 2D, and the 1,3-BDO pathway comprises 4A, 4K, 40, 4N and 4G, In vet another embodiment, the acetyl-CoA pathway comprises 2A, 213, 2C and 21), and the 1,3-13DO pathway comprises 4A, 4K, 4L, 4F and 4G. In certain embodiments, the acetyl-CoA pathway optionally further comprises 2G, 3H, 31, 3, or any combination thereof. In some embodiments, the non-naturally occurring eukaryotic organism comprises exogenous nucleic acids, wherein each of the exogenous nucleic acids encodes a different acetyl-CoA pathway or 1,3-13DO pathway enzyme. 1001491 in other embodiments, (1) the acetyl-CoA pathway comprises 2A, 2B, 2E and 2F-; and (2) the 1,3-BDO pathway comprises (i) 4A, 4E, 4F and 4G; (ii) 4A, 4B and 4D; (iii) 4A, 4E, 4C and 4D; (iv) 4A, 4H and 4J; (v) 4A, 4H, 41 and 4G; (vi) 4A, 4H, 4M, 4N and 4G; (vii) 4A 4K, 40, 4N and 4G; or (viii) 4A, 4K, 4L, 4F and 4G. In some embodiments,. the acetyl-CoA pathway comprises 2A, 2B, 2E. and 2F, and the 1,3-BDO pathway comprises 4A, 4E, 4Fand 4G. In other embodiments, the acetyl-CoA pathway comprises 2A. 213, 2E and 2F, and the 1,3-BDO pathway comprises 4A, 413 and 4D. In one embodiment, the acetyl-CoA pathway comprises 2A, 2B. 2E and 2F, and the 1,3-BDO pathway comprises 4A, 4E, 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises 2A, 213, 2E and 21F, and the 1,3-BDO pathway comprises 4A, 4H and 4J. In other embodiments, the acetyl-CoA pathway comprises 2A, 213, 2E and 2F, and the I,3 -BDO pathway comprises 4A, 41-1, 41 and 4G. In certain embodiments, the acetyl-CoA pathway comprises 2A, 213, 2E and 2F, and the 1,3-13DO pathway comprises 4A, 41-1, 4M, 4N and 4G. In another embodiment. the acetyl-CoA pathway comprises 2A. 213, 2E and 2F, and the 1,3-13DO pathway comprises 4A, 4K, 40, 4N and 4G. In yet another embodiment, the acetyl CoA pathway comprises 2A, 2B, 2E and 2F. and the l,3-BDO pathway comprises 4A. 4K, 4L, 4F and 4G. In certain embodiments, the acetyl-CoA pathway optionally further comprises 2G, 33H, 31, 3J, or any combination thereof In some embodiments, the non-naturally occurring -74eukaryotic organism comprises exogenous nucleic acids, wherein each of the exogenous nucleic acids encodes a different acetyl-CoA pathway or 1,3-3DO pathway enzyme. [00150] In other embodiments, (1) the acetyl-CoA pathway comprises 2A, 2C, 2E and 2F; and (2) the 1,3-BDO pathway comprises (i) 4A, 4E, 4F and 4G; (ii) 4A, 4B and 4D; (iii) 4A, 4E, 4C and 4D; (iv) 4A, 4H and 4J; (v) 4A, 41], 41 and 4G; (vi) 4A, 4H, 4M, 4N and 4G; (vii) 4A, 4K, 40, 4N and 4G; or (viii) 4A, 4K, 4L, 4F and 4G. In some embodiments, the acetyl-CoA pathway comprises 2A 2C, 2E and 2F, and the 1,3-BDO pathway comprises 4A, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises 2A, 2C, 2E and 2F, and the 1 ,3-13DO pathway comprises 4A, 4B and 4D. In one embodiment, the acetyl-CoA pathway comprises 2A. 21C, 2E and 2F, and the 1,3-BDO pathway comprises 4A, 4E, 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises 2A, 2C, 2.E and 2F, and the 1,3-BDO pathway comprises 4A, 41-1 and 4J. In other embodiments, the acetyl-CoA pathway comprises 2A, 2C, 2E and 2F, and the I,3-BDO pathway comprises 4A, 4H, 41 and 4G. In certain embodiments, the acetyl-CoA pathway comprises 2A, 2C, 2E and 21F, and the I,3-BDO pathway comprises 4A, 41-1, 4M, 4N and 4G. In another embodiment, the acetyl-CoA pathway comprises 2A, 2C, 2E and 2F, and the 1,3-BDO pathway comprises 4A, 4K, 40, 4N and 4G. In yet another embodiment, the acetyl CoA pathway comprises 2A, 2C, 21 and 21F, and the 1,3-BDO pathway comprises 4A, 4K, 4L, 4F and 4G. In certain embodiments, the acetyl-CoA pathway optionally further comprises 2G, 3H, 31, 33, or any combination thereof, In some embodiments, the non-naturally occurring eukaryotic organism comprises exogenous nucleic acids, wherein each of the exogenous nucleic acids encodes a different acetyl-CoA pathway or 1,3-BDO pathway enzyme. [00151] In other embodiments, (1) the acetyl-CoA pathway comprises 2A, 2B, 2C, 2E and 2F; and (2) the 1,3-BDO pathway comprises (i) 4A, 4E, 4F and 4G; (ii) 4A, 4B and 4D; (iii) 4A, 4E, 4C and 4D; (iv) 4A, 4H and 4J; (v) 4A, 4H, 4I and 4G; (vi) 4A, 4H, 4M. 4N and 4G; (vii) 4A., 4K, 40, 4N and 4G; or (viii) 4A, 4K, 4L, 41 and 4G. In some embodiments, the acetyl-CoA pathway comprises 2A, 2B, 2C, 2E and 2F, and the 1,3-BDO pathway comprises 4A, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises 2A, 2B, 2C, 21E and 2F, and the 1,31-BDO pathway comprises 4A, 4B and 4D. In one embodiment, the acetyl-CoA pathway comprises 2A, 213, 2C, 2E and 2F, and the 1,3-BDO pathway comprises 4A, 4E, 4C and 4D. In -75some embodiments, the acetyl-CoA pathway comprises 2A, 2B, 2C. 21E and 2F, and the 1,3 13DO pathway comprises 4A, 4H and 4J. In other embodiments, the acetyl-CoA pathway comprises 2A, 213, 2C, 2E and 2F, and the 1,3-13DO pathway comprises 4A, 4H, 41 and 4G. In certain embodiments, the acetyl-CoA pathway comprises 2A, 2B, 2C, 2E and 2F, and the 1,3 BDO pathway comprises 4A, 4H, 4M, 4N and 4G. In another embodiment, the acetyl-CoA pathway comprises 2A, 213, 2C, 2E and 21, and the 1,3-BDO pathway comprises 4A, 4K, 40, 4N and 4G. In yet another embodiment, the acetyl-CoA pathway comprises 2A, 213, 2C, 2E and 2F, and the 1.3-BDO pathway comprises 4A, 4-K, 4L, 4F and 4G. In certain embodiments. the acetyl-CoA pathway optionally further comprises 2G, 31-, 31, 3J, or any combination thereof. In some embodiments, the non-naturally occurring eukaryotic organism comprises exogenous nucleic acids, wherein each of the exogenous nucleic acids encodes a different acetyl-CoA pathway or I,3-BDO pathway enzyme. 1001521 In some embodiments, (1) the acetyl-CoA pathway comprises 2A, 213, 2E, 2K and 2L; and (2) the I .3-BDO pathway comprises (i) 4A, 4E, 4F and 4G; (ii) 4A, 4B and 4D; (iii) 4A, 4E, 4C and 4D; (iv) 4A, 4H and 4J; (v) 4A, 4H, 41 and 4G; (vi) 4A, 4H, 4M, 4N and 4G; (vii) 4A, 4K, 40, 4N and 4G- or (viii) 4A, 4K, 4L, 4F and 4G. In some embodiments, the acetyl-CoA pathway comprises 2A, 2B, 2E, 2K and 21, and the 1,3-BDO pathway comprises 4A, 4E, 411 and 4G. In other embodiments, the acetyl-CoA pathway comprises 2A, 2B, 2E, 2K and 2L, and the 1,3-BDO pathway comprises 4A, 413 and 4D. In one embodiment, the acetyl-CoA pathway comprises 2A, 2B, 2E, 2K and 2L, and the 1,3-BDO pathway comprises 4A, 4E, 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises 2A, 2B, 2E, 2K and 21, and the ],3 BDO pathway comprises 4A, 4H and 4J. In other embodiments, the acetyl-CoA pathway comprises 2A, 213, i2 K and 2L, and the 1,3-EDO pathway comprises 4A, 41, 41 and 4G. In certain embodiments, the acetyl-CoA pathway comprises 2A, 213, 211, 2K and 2L, and the I,3 BDO pathway comprises 4A, 4H, 4M, 4N and 4G. In another embodiment, the acetyl-CoA pathway comprises 2A, 213, 2E, 2K and 21, and the 1,3-BDO pathway comprises 4A, 4K, 40, 4N and 4G. In yet another embodiment, the acetyl-(CoA pathway comprises 2A, 213, 2E, 2K and 2L and the 1,3-BDO pathway comprises 4A, 4K, 4L, 4F and 4G. In certain embodiments, the acetyl-CoA pathway optionally further comprises 2G, 3H, 31, 3J, or any combination thereof. In some embodiments, the non-naturally occurring eukaryotic organism comprises exogenous -76nucleic acids, wherein each of the exogenous nucleic acids encodes a different acetyl-CoA pathway or 1,3-BDO pathway enzyme. [00153] In some embodiments, (1) the acetyi-CoA pathway comprises 2A, 2C, 2E, 2K and 2L; and (2) the 1,3-BDO pathway comprises (i) 4A, 4E, 4F and 4G; (ii) 4A, 4B and 4D; (iii) 4A, 4E, 4C and 4D; (iv) 4A, 4H and 4J; (v) 4A, 4H, 41 and 4G; (vi) 4A, 4H, 4M, 4N and 4G (vii) 4A, 4K, 40, 4N and 4G; or (viii) 4A, 4K, 4L, 41 and 4G. In some embodiments, the acetyl-CoA pathway comprises 2A, 2B, 2E, 2K and 2L, and the 1,3-BDO pathway comprises 4A, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises 2A, 2B, 2E, 2K and 2L, and the 1,3-BDO pathway comprises 4A, 4B and 4D. In one embodiment, the acetyl-CoA pathway comprises 2A, 2C, 2E, 2K and 2L, and the 1,3-13DO pathway comprises 4A, 41, 4C and 41). In some embodiments, the acetyl-CoA pathway comprises 2A, 2C, 2E, 2K and 2L, and the 1,3 BDO pathway comprises 4A, 41-1 and 4J. In other embodiments, the acetyl-CoA pathway comprises 2A, 2C, 2E, 2K and 2L, and the 1,3-BDO pathway comprises 4A, 4H, 41 and 4G. In certain embodiments, the acetyb-Co-A pathway comprises 2A, 2C, 2E, 2K and 2L, and the 1,3 BDO pathway comprises 4A, 4H, 4M, 4N and 4G. In another embodiment, the acetyl-CoA pathway comprises 2A, 2C, 2E, 2K and 2L, and the 1,3-BDO pathway comprises 4A, 4K, 40, 4N and 4G. In yet another embodiment, the acetyl-CoA pathway comprises 2A, 2C, 2E, 2K and 2L and the 1,3-BDO pathway comprises 4A. 4K, IL, IF and 4G. In certain embodiments, the acetyl-CoA pathway optionally further comprises 2G, 31-1, 31, 3J, or any combination thereof. In some embodiments, the acetyl-CoA pathway further comprises 2G, 3H, 31, 3J, or any combination thereof. In certain embodiments, the aceti-CoA pathway further comprises 2G. In some embodiments, the acetyl-CoA pathway further comprises 3H. In other embodiments, the acetyl-CoA pathway further comprises 311. In yet other embodiments, the acetyl-CoA pathway further comprises 3J. In some embodiments, the acetyl-CoA pathway further comprises 2G and 3H. In an embodiment, the acetyl-CoA pathway further comprises 2G and 31. In one embodiment, the acetyl-CoA pathway further comprises 2G and 3.1. In some embodiments, the acetyl-CoA pathway further comprises 3H and 31. In other embodiments, the acetyl-CoA pathway further comprises 311 and 33. In certain embodiments, the acetyi-CoA pathway further comprises 31 and 3J. In another embodiment, the acetyl-CoA pathway further comprises 2G, 3H and 31. In yet another embodiment, the acetyl-CoA pathway further comprises 2G, 3H and 3J. -77- In some embodiments, the acetyl-CoA pathway further comprises 2G, 31 and 3J. In other embodiments, the acetvl-CoA pathway further comprises 31, 31 and 33. In some embodiments, the non-naturally occurring eukaryotic organism comprises exogenous nucleic acids, wherein each of the exogenous nucleic acids encodes a different acetyl-CoA pathway or I,3-BDO pathway enzyme. [001541 In some embodiments, (1) the acetyl-CoA pathway comprises 2A, 2B, 2C, 2E, 2K and 2L; and (2) the 1,3-BDO pathway comprises (i) 4A, 4E, 4F and 4G; (ii) 4A, 4B and 4D; (iii) 4A, 4E, 4C and 4D; (iv) 4A, 41 and 4.; (v) 4A, 41-1, 41 and 4G; (vi) 4A, 4H, 4M, 4N and 4G; (vii) 4A, 4K, 40, 4N and 4G; or (viii) 4A, 4K, 4L, 4F and 4G. In some embodiments, the acetyl-CoA pathway comprises 2A, 213, 2C, 2E, 2K and 2L, and the 1,3-BDO pathway comprises 4A, 4E, 4F and 4G. In other embodiments, the acety-CoA pathway comprises 2A, 2B, 2C, 2E, 2K and 2L, and the I ,3-BDO pathway comprises 4A, 4B and 4D. In one embodinenit, the acetyl-CoA pathway comprises 2A, 2B, 2C, 2E, 2K and 2L, and the 1,3-BDO pathway comprises 4A, 4E, 4C and 4D. In some embodiments, the acetyl-Co-A pathway comprises 2A, 2 B, 2C, 2E, 2K and 2L, and the 1,3-BDO pathway comprises 4A, 4H and 4J. In other embodiments, the acetyl-CoA pathway comprises 2A, 2B, 2C,. 2E, 2K and 2L, and the 1,3-BDO pathway comprises IA, 4H, 41 and 4G, In certain embodiments, [he acetyl-CoA pathway comprises 2A, 213, 2C, 2E, 2K and 2L, and the 1,3-BDO pathway comprises 4A, 4H, 4M, 4N and 4G. In another embodiment, the acetyl-CoA pathway comprises 2A, 213, 2C, 21E, 2K and 2L, and the 1,3-BDO pathway comprises 4A, 4K, 40, 4N and 4G. In yet another embodiment, the acetyl-CoA pathway comprises 2A, 2B, 2C, 2E, 21K and 2L, and the 1,3-BDO pathway comprises 4A, 4K, 4L, 4F and 4G. In certain embodiments, the acetyl-CoA pathway optionally further comprises 2G, 3H, 31, 3J, or any combination thereof. In sonie embodiments, the non-naturally occurring eukaryotic organism comprises exogenous nucleic acids, wherein each of the exogenous nucleic acids encodes a different acetyl-CoA pathway or 1,3-BDO pathway enzyme. [001551 In certain embodiments, (1) the acetyl-CoA pathway comprises 5A, 5B, 5C, SD 5E. SF, 5G, 51H, 51, 5i or any combination of 5A, 5B, 5C, 5D, SE, SF, 5G, 5H, 51 and 5i thereof, wherein 5A is a pyruvate oxidase (acetate forming); 5B is an acetyl-CoA synthetase, ligase or transferase; 5C is an acetate kinase; 5D is a phosphotransacetylase; 5E is a pyruvate -78decarboxylase; 5F is an acetaldehyde dehydrogenase; 5G is a pyruvate oxidase (acetyl-phosphate forming); 5H is a pyruvate dehydrogenase, pyruvate:ferredoxin oxidoreductase or pyruvate formate lyase; 5I acetaldehyde dehydrogenase (acylating); and 5J is a threonine aldolase; and (2) the I,3-BDO path way comprises 4A, 4B, 4C, 4D, 4E, 4F, 4G, 411, 41, 4J, 4K, 4L, 4M, 4N or 40, or any combination of 4A, 4B, 4C, 4D, 4E, 4F, 4G, 4H, 41, 4J, 4K, 4L, 4M, 4N and 40 thereof; wherein 4A is an acetoacetyl-CoA thiolase; wherein 4B is an acetoacetyl-CoA reductase (CoA dependent, alcohol forming); wherein 4C is a 3-oxobutyraldehyde reductase (aldehyde reducing); wherein 4D is a 4-hydroxy,2-butanone reductase; wherein 4E is an acetoacetyl-CoA reductase (CoA-dependent, aldehyde forming); wherein 4F is a 3-oxobutyraldehyde reductase (ketone reducing); wherein 4G is a 3-hydroxybutyraldehyde reductase; wherein 4H is an acetoacetyl-CoA reductase (ketone reducing); wherein 41 is a 3-hydroxybutvryl-CoA reductase aldehydee forming); wherein 4J is a 3-hydroxybutyryl-CoA reductase (alcohol forming); wherein 4K is an acetoacetyl-CoA transferase, an acetoacetyl-CoA hydrolase, an acetoacetyl-CoA synthetase, or a phosphotransacetoacetylase and acetoacetate kinase; wherein 4L is an acetoacetate reductase; wherein 4M1 is a 3-hydroxybutyryl-CoA transferase, hydrolase, or synthetase; wherein 4N is a 3-hydroxybutyrate reductase; and wherein 40 is a 3-hydroxybutyrate dehydrogenase. In certain embodiments, 5B is an acetyl-CoA synthetase. In another embodiment, 513 is an acetvl-CoA ligase. In other embodiments, 5B is an acetyl-CoA transferase. In some embodiments, 5H is a pyruvate dehydrogenase. In other embodiments, 5H is a pyruvate:ferredoxin oxidoreductase. In yet other embodiments, 5-1 is a pyruvate formate lyase. In certain embodiments, 4K is an acetoacetyl-CoA transferase. In other embodiments, 4K is an acetoacetyl-CoA hydrolase. In some embodiments, 4K is an acetoacetyi-CoA synthetase. In other embodiments, 4K is a phosphotransacetoacetylase and acetoacetate kinase. in certain embodiments, 4M is a 3-hydroxybutyryl-CoA transferase. In some embodiments, 4M is a 3 hydroxvbutyryl-CoA, hydrolase. In vet other embodiments, 4M is a 3-hydroxybutyryl-CoA synthetase. [001561 In some embodiments, the acetyl-CoA pathway is an acetyl-CoA pathway depicted in FIG. 5, and the 1,3-13DO pathway is a 1,3-BDO pathway depicted in FIG. 4. Exemplary sets of acetyl-CoA pathway enzynies, according to FIG. 5, are 5A and 5B; 5A, 5C and 5D; 5G and 5D; SE, 5F, SC and 5D; 5J and 5i; 5J, 5F and 5B: and 511. Exemplary sets of 1,3-BDO pathway -79enzymes to convert acetyl-CoA to 1,3-BDO, according to FIG. 4, include 4A, 4E, 4F and 4G; 4A, 413 and 41D; 4A, 4E, 4C and 4D; 4A, 4[I and 4J; 4A, 4H, 41 and 4G; 4A, 4H, 4M/, 4N and 4G; 4A, 4K, 40, 4N and 4G; or 4A, 4K, 4L, 4F and 4G. [001571 In some embodiments, (1) the acetyl-CoA pathway comprises (i) 5A and 5B; (ii) 5A, 5C and 5D; (iii) SE, 5F, SC and 5D; (iv) 5G and 5D; (v) 5J and 5; (vi) 5J, 5F and 5B; or (vii) 5H; and (2) the 1,3-BDO pathway comprises () 4A, 4E, 4F and 4G; (ii) 4A, 4B and 4D; (iii) 4A, 4E, 4C and 4D; (iv) 4A, 4H and 4J; (v) 4A, 4H, 41 and 4G; (vi) 4A, 4H, IM, IN and 4G; (vii) 4A, 4K, 40, 4N and 4G; or (viii) 4A, 4K, 4L, 4F and 4G. [001581 In some embodiments, the acetvl-CoA pathway comprises 5A and 513; and the 1,3 BDO pathway comprises 4A, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises 5A and 5B; and the 1,3-BDO pathway comprises 4A, 413 and 41. In some embodiments, the acetyl-CoA pathway comprises 5A and 5B; and the 1,3-BDO pathway comprises 4A, 4E, 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises 5A and 5B; and the 1,3-BDO pathway comprises 4A, 4H and 4J. In some embodiments, the acetyl CoA pathway comprises 5A and 5B; and the 1,3-BDO pathway comprises 4A, 4H, 41 and 4G. In some embodiments, the acetyl-CoA pathway comprises 5A and 513; and the 1,3-3DO pathway comprises 4A, 4H, 4M, 4-1N and 4G. In some embodiments, the acetyl-CoA pathway comprises 5A and 513; and the 1,3-3DO pathway comprises 4A, 4K, 40, 4N and 4G, In some embodiments, the acetyl-CoA pathway comprises 5A and 5B; and the 1 ,3-BDO pathway comprises 4A, 4K, 4L, 4F and 4G. [001591 In some embodiments, the acetyl-CoA pathway comprises 5A, 5C and 5D; and the 1,3-BDO pathway comprises 4A, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises SA, 5C and 5D; and the 1,3-BDO pathway comprises 4A, 4B and 4D. In some embodiments, the acetvl-CoA pathway comprises 5A, 5C and SD; and the 1,3-BDO pathway comprises 4A, 4E, 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises 5A, SC and 5D; and the 1,3-BDO pathway comprises 4A, 41-1 and 4J. In some embodiments, the acetyl-CoA pathway comprises -A, 5C and 5D; and the 1,3-BDO pathway coniprises 4A, 41-, 41 and 4G. In some embodiments, the acetyl-CoA pathway comprises SA, 5C and 5D; and the 1,3-BDO pathway comprises 4A, 4H, 4N1, 4N and 4G. In some embodiments, -80the acetyl-CoA pathway comprises 5A, 5C and SD; and the 1,3-BDO pathway comprises 4A, 4K, 40, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises 5A, SC and 5D; and the 1,3-BDO pathway comprises 4A, 4K, 4L, 4F and 4G. [001601 In some embodiments, the acetyl-CoA pathway comprises 5E, 5F, 5C and 5D; and the 1,3-BDO pathway comprises 4A, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises 5E, 5F, 5C and 5D; and the 1,3-BDO pathway comprises 4A, 4B and 4D. In some embodiments, the acetyl-CoA pathway comprises 5E, 5F, 5C and SD; and the 1,3-BDO pathway comprises 4A, 4E, 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises 5E, 5F, 5C and 5D; and the 1,3-BDO pathway comprises 4A, 4H and 4J. In some embodiments, the acetyl-CoA pathway comprises 5E, 5F, 5C and 5); and the 1,3-BDO pathway comprises 4A, 4H, 4I and 4G. In some embodiments, the acetyl-CoA pathway comprises 5E, SF, SC and 5D; and the I ,3-BDO pathway comprises 4A, 41-1, 4M, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises 5E, 5F, 5C and 5D; and the 1,3-BDO pathway comprises 4A, 4K, 40, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises 5E, 5F, 5C and 5D; and the 1,3-BDO pathway comprises 4A, 4K, 4L, 4F and 4G. 1001611 In some embodiments, the acetyl-CoA pathway comprises 5G and 5D; and the 1,3 BDO pathway comprises 4A, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises 5G and 5D; and the 1,3-3DO pathway comprises 4A, 4B and 4D. In some embodiments, the acetyl-CoA pathway comprises 5G and 5D- and the 1,3-BDO pathway comprises 4A, 4E, 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises 5G and 5D and the 1,3-BDO pathway comprises 4A, 4H and 4J. In some embodiments, the acetyl CoA pathway comprises 5(3 and 5D; and the 1,3-BDO pathway comprises 4A, 411, 41 and 4G. In some embodiments, the acetyl-CoA pathway comprises 5G and 5D; and the 1,3-BDO pathway comprises 4A, -4H, 4M, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises SG and 5D; and the 1,3-BDO pathway comprises 4A, 4K, 40, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises 5G and SD; and the 1,3-BDO pathway comprises 4A, 4K, 4L, 4F and 4G. [00162] In some embodiments, the acetyl-CoA pathway comprises 5J and 5I; and the 1,3-BDO pathway comprises 4A, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway -81comprises 5J and 51; and the 1,3-BDO pathway comprises 4A, 4-B and 4D. In some embodiments, the acetv-CoA pathway comprises 5J and 51; and the 1,3O31)0 pathway comprises 4A, 4E, 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises 5J and 5I; and the ,3-BDO pathway comprises 4A, 41- and 4J. In some embodiments, the acetyl-CoA pathway comprises 5J and 51; and the 1,3-BDO pathway comprises 4A, 4H, 41 and 4G. In some embodiments, the acetyl-CoA pathway comprises 5J and 5I; and the 1,3-BDO pathway comprises 4A, 4H, 4M, 4N and 4G. In some embodiments, the acetvl-CoA pathway comprises 5J and 5I; and the 1,3-BDO pathway comprises 4A, 4K. 40, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises 5i and 5I; and the I,3-BDO pathway comprises 4A, 4K, 4L, 4F and 4G. [001631 In some embodiments, the acetyl-CoA pathway comprises 5J, 5F and 5B; and the 1,3 BDO pathway comprises 4A, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises 5J, 5F and SB; and the 1,3-BDO pathway comprises 4A, 4B and 4D. In some embodiments, the acetyl-CoA pathway comprises 5, 5F and 5B; and the 1,3-BDO pathway comprises 4A, 4E, 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises 5J, 5F and 5B: and the 1,3-BDO pathway comprises 4A, 4H and 4J. In some embodiments, the acetyl CoA pathway comprises 5J, 5F and 5B; and the 1,3-BDO pathway comprises 4A, 411, 41 and 4G. In some embodiments, the acetyl-CoA pathway comprises 5J, SF and 5B; and the 1,3-BDO pathway comprises 4A, 41-I, 4M\, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises 5J, 5F and 5B; and the I,3-BDO pathway comprises 4A, 4K, 40, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises 5J, 5F and 5B; and the I ,3-BDO pathway comprises 4A, 4K, 4L, 4F and 4G. [001641 In some embodiments, the acetyl-CoA pathway comprises 5H; and the 1,3-BDO pathway comprises 4A, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises 5I-I; and the 1,3-BDO pathway comprises 4A, 413 and 41). In some embodiments, the acetyl-CoA pathway comprises 5H; and the 1 ,3-BDO pathway comprises 4A, 4E, 4C and 41D. In some embodiments, the acetyl-CoA pathway comprises 5-I; and the 1,3-BDO0 pathway comprises 4A, 4H and 4J. In some embodiments, the acetyl-CoA path-way comprises 5H; and the I,3-BDO pathway comprises 4A, 41-1, 41 and 4G. In some embodiments, the acetyl-CoA -82pathway comprises 5H; and the 1,3-BDO pathway comprises 4A, 4-H, 4M, 4-N and 4G. In some embodiments, the acetyl-CoA pathway comprises 51-1; and the I,3-BDO pathway comprises 4A, 4K, 40, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises 5H; and the 1,3 BDO pathway comprises 4A, 4K, 4L, 4F and 4G. [001651 In certain embodiments, (1) the acetyl-CoA pathway comprises 6A, 6B, 6C, 6D or 6E, or any combination of 6A, 6B, 6C, 6D and 6E thereof, wherein 6A is mitochondrial acetylearnitine transferase; 6B is a peroxisomal acetylcamitine transferase; 6C is a cytosolic acetylcarnitine transferase; 61) is a mitochondrial acetylcarnitine translocase; and 6E. is peroxisonial acetylearnitine translocase; and (2) the 1,3-BDO pathway comprises 4A, 4B, 4C, 4[), 4E, 4F, 4G, 41-1, 41, 4J, 4K, 4L, 4M, 4N or 40, or any combination of 4A, 413, 4C, 4[), 4E, 4F, 4G, 4H, 41, 4J, 4K, 4L, 4M, 4N and 40 thereof; wherein 4A is an acetoacetyl-CoA thiolase; wherein 4B is an acetoacetyl-CoA reductase (CoA-dependent, alcohol forming); wherein 4C is a 3-oxobutyraidehyde reductase aldehydee reducing); wherein 4D is a 4-hydroxy,2-butanone reductase; wherein 4E is an acetoacetyl-CoA reductase (CoA-dependent, aldehyde forning); wherein 4F is a 3-oxobutyraldehyde reductase (ketone reducing); wherein 4G is a 3 hydroxybutyraldehyde reductase; wherein 4H is an acetoacetyl-CoA reductase (ketone reducing); wherein 41 is a 3-hydroxybutvryl-CoA reductase (aldehyde forming); wherein 4J is a 3-hydroxybutyryl-CoA reductase (alcohol forming); wherein 4K is an acetoacetyl-CoA transferase, an acetoacetyl-CoA hydrolase, an acetoacetyl-CoA synthetase, or a phosphotransacetoacetylase and acetoacetate kinase; wherein 4L is an acetoacetate reductase; wherein 4M is a 3-hydroxybutyryl-CoA transferase, hydrolase, or synthetase; wherein 4N is a 3 hydroxybutyrate reductase; and wherein 40 is a 3-hydroxybutyrate dehydrogenase. In certain embodiments, 4K is an acetoacetyl-CoA transferase. In other embodiments, 4K is an acetoacetyl-CoA hydrolase. In some embodiments, 4K is an acetoacetyl-CoA synthetase. In other embodiments, 4K is a phosphotransacetoacetylase and acetoacetate kinase. In certain embodiments, 41 is a 3-hydroxybutyryl-CoA transferase. In some embodiments, 41 is a 3 hydroxybutyryl-CoA, hydrolase. In yet other embodiments, 4M is a 3-hydroxybutyryl-CoA synthetase. -83- [001661 In some embodiments, the acetyl-CoA pathway is an acetyl-CoA pathway depicted in FIG. 6, and [he I,3-43DO pathway is a I,3-BDO pathway depicted in FIG 4. Exemplary sets of acetyl-CoA pathway enzymes, according to FIG. 6, are 6A, 6D and 6C; and 6B, 6E and 6C. Exemplary sets of 1,3-BDO pathway enzymes to convert acetyl-CoA to 1,3-BDO, according to FIG. 4. include 4A, 4E, 4F and 4G; 4A, 4B and 4D; 4A, 4E, 4C and 41); 4A 4H and 4J; 4A, 4H, 41 and 4G; 4A, 411, 4M, 4N and 4G; 4A, 4K, 40, 4N and 4G; or 4A, 4K, 4L, 4F and 4G. [001671 In one embodiment, (1) the acetyl-CoA pathway comprises (i) 6A, 6D and 6C; or (ii) 613, 61 and 6C; and (2) the I,3-BDO pathway comprises (i) 4A, 4E, 4F and 4G; (ii) 4A, 413 and 4D; (iii) 4A, 4E, 4C and 4D; (iv) 4A, 4H and 4J; (v) 4A, 4H, 41 and 4G; (vi) 4A, 4H, 4M, 4N and 4G; (vii) 4A, 4K, 40, 4N and 4G; or (viii) 4A, 4K, 4L, 4F and 4. 1001681 In some embodiments, the acetyl-CoA pathway comprises 6A, 61) and 6(7 and the 1,3-BDO pathway comprises 4A, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises 6A, 6D and 6C; and the 1,3-BDO pathway comprises 4A, 4B and 4D. In some embodiments, the acetyl-CoA pathway comprises 6A, 6D and 6C; and the 1,3-BDO pathway comprises 4A, 4E, 4C and 4D, In some embodiments, the acetyl-CoA pathway comprises 6A, 6D and 6C; and the 1,3-3DO pathway comprises 4A, 41-1 and 4J. In some embodiments, the acetyl-CoA pathway comprises 6A, 6D and 6C; and the 1,3-BDO pathway comprises 4A, 41, 41 and 4G. In some embodiments, the acetyl-CoA pathway comprises 6A, 6D and 6C; and the 1,3-BDO pathway comprises 4A, 4H, 4M, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises 6A, 6D and 6C; and the 1,3-BDO pathway comprises 4A, 4K, 40, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises 6A, 6D and 6C; and the 1,3-BDO pathway comprises 4A, 4K, 4L, 4F and 4G. [00169] In some embodiments, the acetyl-CoA pathway comprises 6B, 6E and 6C; and the 1,3 13D) pathway comprises 4A, 41E, 4F and 4G1. In other embodiments, the acetyl-CoA pathway comprises 6B, 6E and 6C; and the 1,3-BDO pathway comprises 4A. 413 and 4D. In some embodiments, the acetyl-CoA pathway comprises 61, 6E and 6(; and the 1,3-3DO pathway comprises 4A, 4E, 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises 6B. 6E and 6C; and the 1,3-BDO pathway comprises 4A, 4H and 4J. In some embodiments, the acetyl-CoA pathway comprises 6B, 6E and 6C; and the 1,3-BDO pathway comprises 4A, 4H, 41 -84and 4G. In some embodiments, the acetyl-CoA pathway comprises 6B, 6E and 6C; and the 1,3 BDO pathway comprises 4A, 4Hf, 4M, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises 6B, 6E and 6C; and the 1,3-BDO pathway comprises 4A, 4K, 40, 4N and 4G, In some embodiments, the acetyl-CoA pathway comprises 613, 6E and 6C; and the 1,3-BDO pathway comprises 4A, 4K, 4L, 4F and 4G. 1001701 In certain embodiments, (1) the acetyl-CoA pathway comprises 0A, I B, 10C, 1OD, JOF, JOG, 10H. 10J, 10K, 1OL, 1GM, JON, or any combination of 10A, JOB, 10C, 1OD, OF, 10(I, 101H. 10.1, 10K, IOL, 10M, ION thereof; and (2) the 1,3-BDO pathway comprises 4A (see also FIG. 10, step 1), 4B, 4C, 4D, IE, IF, 4G, 4H, 41, 4J, 4K IL. 4M, 4N or 40, or any combination of 4A, 413, 4C, 41), 4E, 4F, 4G, 4Hf, 41, 4J, 4K, 4L, 4M, 4N and 40 thereof. In one embodiment. 1OA is a PEP carboxylase. In another embodiment, I0A is a PEP carboxykinase. In an embodiment, I OF is an oxaloacetate dehydrogenase. In other embodiments, JOF is an oxaloacetate oxidoreductase. In one embodiment, 10K is a malonyl-CoA synthetase. In another embodiment, I OK is a malonyl-CoA transferase. In one embodiment, 1GM is a malate dehydrogenase. In another embodiment, 10M is a malate oxidoreductase. In other embodiments, JON is a pyruvate kinase. In some embodiments, JON is a PEP phosphatase. In certain embodiments, 4K is an acetoacetyl-(oA transferase. In other embodiments, 4K is an acetoacetvl-CoA hydrolase. In some embodiments. 4K is an acetoacetyl-CoA synthetase. In other embodiments, 4K is a phosphotransacetoacetylase and acetoacetate kinase. In certain embodiments, 4M is a 3-hydroxybutyryl-CoA transferase. In some embodiments, 4M is a hydroxybutryl.-CoA, hydrolase. In yet other embodiments, 4M is a 3-hydroxybutyryl-CoA synthetase. [001711 In some embodiments, the acetyl-CoA pathway is an acetyl-CoA pathway depicted in FIG. JO, and the 1,3-BDO pathway is a 1,3-BDO pathway depicted in FIG. 4. Exemplary sets of acetyl-CoA pathway enzymes, according to FIG. 10, are I GA, 10B and 10C; JON, 10H, 10B and JOC; ON 0L, 1GM, JOB and 10(C; JOA, 10B, JOG and bOD; ON, 101H, JOB, JOG and JOD; ION, IOL, IN, 10B, 10G and 101D; 10A, 10B, I0J, 10K and 101); ION, bOH, 1013, 10.1, 10K and ID; ION, 1OL, 10M, 1GB, bOJ, 10K and 1OED; 1OA, JOF and 10D; ION, 10,IH, 1OF and 1OD; and ION, 1OL, IOM, 1 OF and 10 D. Exemplary sets of 1,3-BDO pathway enzymes to convert -85acetyl-CoA to 1,3-BDO, according to FIG. 4, include 4A, 4E, 4F and 4G; 4A, 4B and 4D; 4A, 4E, 4C and 4D; 4A, 4H and 4J; 4A, 41], 41 and 4G; 4A, 4H, 4M, 4N and 4G; 4A, 4K, 40, 4N and 4G; or 4A, 4K, 4L, 4F and 4G. [001721 In one embodiment, (1) the acetyl-CoA pathway comprises (i) 10 A, 1GB and 10C; (ii) ION, 10H, 10B and 10C; (iii) ION, IOL, 10M, 10B and 10C; (iv) 10A, 1013, 1OG and 1OD; (v) ION, lOH, 1OB, 1OG and 1OD; (vi) ION, IOL, 10M, 1OB, 1OG and 1OD; (vii) I0A, 1OB, 10J, 10K and 1OD; (viii) IN, 10, OB, 1OJ, 10K and IOD; (ix) ION, 1OL, 1GM, 1OB, 1OJ, 10K and IOD; (x) I0A, 10F and 10D; (xi) ION, 10kH, 1OF and 101); or (xii) ION, 1 OL, 10M, lOF and 101); and (2) the 1,3-BDO pathway comprises (i) 4A, 4E, 4F and 4G; (ii) 4A, 4B and ID (iii) 4A, 4E, 4C and 41); (iv) 4A, 4H and 4J; (v) 4A, 41], 41 and 4G; (vi) 4A, 41-1, 4M, 4N and 4G; (vii) 4A, 4K, 40, 4N and 4G; or (viii) 4A, 4K, 4L, 4F and 4G. [001731 In some embodiments, the acetyl-CoA pathway comprises I0A, lOB and 10C; and the 1,3-BDO pathway comprises 4A, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises 10A, lOB and 10C; and the 1,3-BDO pathway comprises 4A, 4B and 4D. In some embodiments, the acetyl-CoA pathway comprises iA, 10B and 10C; and the 1,3-BDO pathway comprises 4A, 4E, 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises lOA, lOB and 10C and the 1,3-BDO pathway comprises 4A, 4H and 4J. In some embodiments, the acetyl-CoA pathway comprises I GA, 1013 and 10(C; and the 1,3-BO)( pathway comprises 4A, 4H, 41 and 4G. In some embodiments, the acetyl-CoA pathway comprises 10A, lOB and 10C; and the 1,3-BDO pathway comprises 4A, 41], 4M, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises 10 A, 1GB and 10C; and the 1,3-BDO pathway comprises 4A, 4K, 40, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises IA, lOB and 10C; and the 1,3-BDO pathway comprises 4A, 4K, 4L, 4F and 4G. [001741 In some embodiments, the acetvl-CoA pathway comprises ION, 10H, 1013 and 10C; and the 1,3-BDO pathway comprises 4A, 4E. 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises ION, 10H, 1013 and 10C; and the 1,3-BDO pathway comprises 4A, 413 and 4D. In some embodiments, the acetyl-CoA pathway comprises ION, I0H, 1GB and 10C; and the 1,3-BDO pathway comprises 4A, 4E, 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises ION, 1OH, lOB and 10C; and the 1 .3-BDO pathway comprises 4A, 4H and -86- 4J. In some embodiments, the acetyl-CoA pathway comprises IN, I0H, 10B and 1OC; and the 1,3-BDO pathway comprises 4A, 4[H, 41 and 4G. In some embodiments, the acetyl-CoA pathway comprises ION, 10H, 1013 and 10C; and the 1,3-BDO pathway comprises 4A, 4H, 4M, 4N and 4G. In some embodiments, the acetvl-CoA pathway comprises 10IN, 101-, 1 0B and I 0C and the 1,3-BDO pathway comprises 4A, 4K, 40, 4N and 4G. In some embodiments, the acetyl CoA pathway comprises ION, 101H, 101B and 10C; and the I,3-BDO pathway comprises 4A, 4K, 4L, 4F and 4G. [00175] In some embodiments, the acetyl-CoA pathway comprises 1 ON, I OL, 10M, 1013 and 10C; and the 1.3-BDO pathway comprises IA, 44E. 4F and 4G. In other embodiments,. the acetvl-CoA pathway comprises ION, 10L, 1M., 1013 and 10C; and the 1,3-BD) pathway comprises 4A, 4B and 4D. In some embodiments, the acetyl-CoA pathway comprises ION, 1OL, 1GM, 10B and 10C; and the 1,3-BDO pathway comprises 4A, 4E, 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises 10N, 10L, 10N', 10B and 10C; and the 1,3 BDO pathway comprises 4A, 41 and 4J. In sone embodiments, the acetyl-CoA pathway comprises ION, IOL, 1GM, 1013 and 10C; and the 1,3-BDO pathway comprises 4A, 4H, 41 and 4G. In some embodiments, the acetyl-CoA pathway comprises ION, IOL, 1GM, 10B and 100; and the I,3-BDO pathway comprises 4A, 41-, 4M, 4N and 4G. In some embodiments, the acetvl-CoA pathway comprises ION, IOL, 1M, 10B and 10C; and the 1,3-BDO pathway comprises 4A, 4K, 40, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises ION, IOL, 1GM, 10B and 10C; and the 1,3-BDO pathway comprises 4A, 4K, 4L, 4F and 4G. 1001761 In some embodiments, the acetyl-CoA pathway comprises I0A, 1GB, lOG and IOD; and the I ,3-BDO pathway comprises 4A, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises I OA, 10B, lOG and 1OD; and the 1,31-BDO pathway comprises 4A, 4B and 4D. In some embodiments, the acetyl-CoA pathway comprises 10A, 1013, lOG and IOD; and the 1,3-BDO pathway comprises 4A, 4E, 4C and 41). In some embodiments, the acetyl-CoA pathway comprises 10A, 10B, 10G and IOD; and the 1,3-BDO pathway comprises 4A, 4H and 4J. In some embodiments, the acetvl-CoA pathway comprises 10A, 1013, 10G and 101); and the I,31-BDO pathway comprises 4A, 4H, 41 and 4G. In some embodiments, the acetyl-CoA pathway comprises lOA, 1013, 10G and IOD; and the 1,3-BDO pathway comprises 4A, 4H, 4M, -87- 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises I0A, 10B, 1OG and 1OD; and the 1,3-BDO pathway comprises 4A, 4K, 40, 4N and 4G. In some embodiments, the acetyl CoA pathway comprises 10A, 10B, 1OG and IOD; and the 1,3-BDO pathway comprises 4A, 4K, 4L, 4F and 4G. [001771 In some embodiments, the acetyl-CoA pathway comprises ION, 101-, 101B, 10G and IOD; and the 1,3-BDO pathway comprises 4A, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises ION, IOH, 10B, 10G and IOD; and the 1.3-BDO pathway comprises 4A, 413 and 4D. In some embodiments, the acetyl-CoA pathway comprises ION, 10H-I, 10B, 10G and IOD; and the 1,3-BDO pathway comprises 4A, 4E, 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises ION, 10H, lOB, I 0G and 101); and the 1,3 BDO pathway comprises 4A, 4H and 4J. In some embodiments, the acetyl-CoA pathway comprises ION, 101-1, 101B, 10G and 10D; and the 1,3-BDO pathway comprises 4A, 41-1, 41 and 4G. In some embodiments, the acetyl-CoA pathway comprises ION, 10H, 10B, lOG and 10D; and the 1,3-BDO pathway comprises 4A, 4H, 4M, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises ION, 10, 1013, 10G and IOD; and the 1,3-BDO pathway comprises 4A, 4K, 40, IN and 4G. In some embodiments, the acetyl-CoA pathway comprises ION, 10H, 1013, lOG and 10D; and the 1,3-3DO pathway comprises 4A, 41K, 4L, 4F7 and 4G. [001781 In some embodiments, the acetvl-CoA pathway comprises ION, 10L, 1 OM, 1013, lOG and 1OD; and the 1,3-13DO pathway comprises 4A, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises ION, IOL, 10M, 101B, lOG and 1 OD; and the 1,3-BDO pathway comprises 4A, 4B and 4D. In some embodiments, the acetyl-CoA pathway comprises ION, IOL, 1 OM, 10B, 10G and IOD; and the 1,3-BDO pathway comprises 4A, 4E, 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises ION, lOL, 10N, 10B, lOG and IOD; and the 1,3-BDO pathway comprises 4A, 4H and 4J. In some embodiments, the acetyl-CoA pathway comprises ION, IOL, IOM, 1013, 10G and 101); and the 1,3-3DO pathway comprises 4A, 41-I, 41 and 4G. In some embodiments, the acetyl-CoA pathway comprises ION. IOL, IOM. 10B, 10G and 101); and the 1,3-131) pathway comprises 4A, 4H, 4M, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises ION, IOL, 1DM, 1013, 1OG and IOD; and the 1,3-BDO pathway comprises 4A, 4K, 40, 4N and 4G. In some embodiments, the acetyl-CoA pathway -88comprises ION, IOL, 1OM, 1013, 10G and 10D; and the 1,3-BDO pathway comprises 4A, 4K, 4L, 4F7 and 4G. [00179] In some embodiments, the acetyl-CoA pathway comprises I0A, 10B, 10J, 10K and 1OD; and the 1,3-13DO pathway comprises 4A, 4E, 4F and 4G. in other embodiments, the acetyl-CoA pathway comprises 10A, 1013, 10J, 10K and 10D; and the 1,3-BDO pathway comprises 4A, 4B and 4D. In some embodiments, the acetyl-CoA pathway comprises l0A, 1013 1OJ, 10K and IOD; and the 1,3-BD0 pathway comprises 4A, 4E, 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises I0A, 1013, 103, 101K and 10D; and the 1,3 BDO pathway comprises 4A, 4H and 4-J. In some embodiments, the acetyl-CoA pathway comprises iOA, 10B, 10J, 10K and 10D; and the 1,3-BDO pathway comprises 4A, 4H, 41 and 4G. In some embodiments, the acetyl-CoA pathway comprises I0A, 10B, 101 10K and IOD; and the 1 ,3-BDO pathway comprises 4A, 41-1, 4M, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises 10A, 10B, 10J, 10K and 10D; and the 1,31-BDO pathway comprises 4A, 4K, 40, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises I0A, 1013, 10J, 10K and 1OD; and the 1,3-BDO pathway comprises 4A, 4K, 4L, 4F and 4G. 1001801 In some embodiments, the acetyl-CoA pathway comprises ION, 101, 1013, 10.1, 10K and 10D; and the 1,3-BDO pathway comprises 4A, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises 1 ON, 10-I, 1013, 103, 101K and 101D; and the 1,3-O13) pathway comprises 4A, 4B and 4D. In some embodiments, the acetyl-CoA pathway comprises 10N, 1 OH. 1013, 1 0J, 10K and 10 D; and the 1,3-BDO pathway comprises 4A, 4E, 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises ION, 10H, 1013, 10J, 10K and IOD; and the 1,3-BDO pathway comprises 4A, 41-1 and 4J. In some embodiments, the acetyl-CoA pathway comprises 10N, 101H, 1013, 10J, 10K and 1OD; and the 1,3-BD0 pathway comprises 4A, 4H, 41 and 4G. In some embodiments, the acetyl-CoA pathway comprises ION, IH, 1013, 10J, 10K and 101D; and the ],3-O13) pathway comprises 4A, 41-1, 4M\, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises ION, 1 10B, 1OJ, 10K and 10D; and the 1.3-BDO pathway comprises 4A, 4K, 40, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises 10N, 10H, 1013, 10J, 10K and 1OD; and the 1,3-BDO pathway comprises 4A, 4K, 4L, 4F and 4G. -89- [001811 In some embodiments, the acetyl-CoA pathway comprises iON, OL , 1M lOB, I0J, 10K and 101); and the 1,3-BDO pathway comprises 4A, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises ION, 1OL, 1GM, 10B, 10J, 10K and 1OD; and the 1,3-BDO pathway comprises 4A, 4B and 4D. In some embodiments, the acetyl-CoA pathway comprises ION, IOL, 10M, 10B, 10J, 10K and 1OD; and the 1,3-BDO pathway comprises 4A, 4E, 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises ION, IGL, 10M, 1GB, 103, 10K and 101); and the 1,3-BDO pathway comprises 4A, 41-1 and 4J. In some embodiments, the acetyl-CoA pathway comprises ION, 10L, 1M, 1OB, I0J, 10K and 1OD; and the 1,3-BDO pathway comprises 4A, 4Ff, 41 and 4G. In some embodiments, the acetvl-CoA pathway comprises ION, IOL, 10M, 1GB, 10J. 10K and IOD; and the 1,3-BDO pathway comprises IA, 41-1, 4M, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises ION, 1OL, 1GM, 10B, 10J, 10K and IOD; and the 1,3-BDO pathway comprises 4A, 4K, 40, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises ION, 1OL, 10M, lOB, 10 J, 10K and 1 D; and the 1,3-BDO pathway comprises 4A, 4K, 4L, 4F and 4G. 1001821 In some embodiments, the acetyl-CoA pathway comprises IA, IOF and 10D; and the 1,3-BDO pathway comprises 4A, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises 10A, 10F and 101) and the 1,3-13DO pathway comprises 4A, 4B and 41). In some embodiments, the acetyl-CoA pathway comprises 10A, 10F and IOD; and the 1,3-BDO pathway comprises 4A, 4E, 4C and 41). In some embodiments, the acetyl-CoA pathway comprises IGA, IOF and IGD; and the 1,3-BDO pathway comprises 4A, 4H and 4J. In some embodiments, the acetyl-CoA pathway comprises I GA, 1 OF and 10 D; and the 1,3-BDO pathway comprises 4A, 4H, 41 and 4G. In some embodiments, the acetyl-CoA pathway comprises 10 A, lOF and IOD; and the 1,3-BDO pathway comprises 4A, 4H, 4M, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises iA, 10 and 101); and the I,3-3D) pathway comprises 4A, 4K. 40, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises I0A, 10 and 101); and the 1,3-BD) pathway comprises 4A, 4K, 4L, 4F and 4G. [001831 In some embodiments, the acetyl-CoA pathway comprises ION, 101-, 1 OF and 1OD; and the 1,3-BDO pathway comprises 4A, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises 10N, 10H, 1 F and I GD; and the 1,3-BDO pathway comprises 4A, 4B and -90- 4D. In some embodiments, the acetyl-CoA pathway comprises ION, I0H, 1OF and 1OD; and the 1,3-BO)( pathway comprises 4A, 41E, 4C and 41). In some embodiments, the acetyl-CoA pathway comprises ION, IOH, 1OF and 10D; and the 1,3-1BDO pathway comprises 4A, 4H and 41 In some embodiments, the acetyl-CoA pathway comprises ION, 101-, 1 OF and I GD; and the 1,3-BDO pathway comprises 4A, 4H, 41 and 4G. In some embodiments, the acetyl-CoA pathway comprises ION, 10H, 1OF and lOD; and the 1,3-BDO pathway comprises 4A, 411, 4M, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises ION, 101-1, iOF and 101) and the 1,3-BDO pathway comprises 4A. 4K, 40, 4-N and 4G. In some embodiments,. the acetyl CoA pathway comprises ION, 101-, IOF and 10D; and the 1,3-43DO pathway comprises 4A, 4K, 4L, 4F and 4G. [001841 In some embodiments, the acetyl-CoA pathway comprises 10N, 10L 10M, IOF and I GD; and the I,3-BDO pathway comprises 4A, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises 10N, 10L. 1GM, LOF and 1OD; and the 1,3-BDO pathway comprises 4A, 4B and 4D. In some embodiments, the acetyl-CoA pathway comprises ION, 10L. 10M, IOF and IOD; and the 1,3-1BDO pathway comprises 4A, 4E, 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises ION, 1OL 1GM, 1OF and 1OD; and the 1,3 13DO pathway comprises 4A, 4[H and 4J. In some embodiments, the acetyl-CoA pathway comprises ION, IOL. 1GM, IOF and IOD; and the 1.3-BDO pathway comprises 4A, 4H, 41 and 4G, In some embodiments, the acetyl-CoA pathway comprises ION, 10L- 10M, iOF and 101); and the 1,3-BDO pathway comprises 4A, 4H, 4M/1, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises ION, I OL. IOM, I OF and I GD; and the I ,3-BDO pathway comprises 4A, 4K, 40, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises ION, 10L. 10M. 1F and IOD; and the 1,3-BDO pathway comprises 4A, 4K, 4L, 4F and 4G. [001851 In an additional embodiment, provided herein is a non-naturally occurring eukaryotic organism having a 1,3-43DO pathway, wherein the non-naturally occurring eukaryotic organism comprises at least one exogenous nucleic acid encoding an enzyme or protein that converts a substrate to a product selected from the group consisting of acetyl-CoA to acetoacetyl-CoA (e.g., 4A); acetoacetyl-CoA to 4-hydroxy-2-butanone (e.g., 4B); 3-oxobutyraldehyde to 4-hydroxy-2 butanone (e.g., 4C); 4-hydroxy-2-butanone to 1,3-BDO (e.g., 4D); acetoacetyl-CoA to 3 -91oxobutyraldehyde (e.g., 4E); 3-oxobutyraldehyde to 3-hydroxybutyridehyde (e.g., 4F); 3 hydroxvbutyrldehyde to 1,3-BD0 (e.g., 4G); acetoacetyl-CoA to 3-hydroxybutyryl-CoA (e.g. 4H); 3-hydroxybutyryl-CoA to 3-hydroxybutyraldehyde (e.g.. 41), 3-hydroxybutyryl-CoA to 1,3 BDO (e.g., 4J); acetoacetyl-CoA to acetoacetate (e.g., 4K); acetoacetate to 3-oxobutyraldehyde (e.g., 4L); 3-hydroxybutyrl-CoA to 3-.hydroxybutyrate (e.g., 4M); 3-hydroxybutyrate to 3 hydroxybutyraldehyde (e.g., 4N); and acetoacetate to 3-hydroxybutyrate (e.g., 40). One skilled in the art will understand that these are merely exemplary and that any of the substrate-product pairs disclosed herein suitable to produce a desired product and for which an appropriate activity is available for the conversion of the substrate to the product can be readily determined by one skilled in the art based on the teachings herein. Thus, provided herein are non-naturally occurring eukaryotic organisms comprising at least one exogenous nucleic acid encoding an enzyme or protein, where the enzyme or protein converts the substrates and products of a 1,3 BDO pathway, such as that shown in FIG. 4. [001861 Also provided herein are non-naturally occurring eukaryotic organisms comprising at least one exogenous nucleic acid encoding an acetyl-CoA carboxylase (7E), an acetoacetyl-CoA synthase (7B) or a combination thereof In certain embodiments of the 1,3-BDO pathways provided herein, including those exemplified in FIG. 4, acetyl-CoA is converted to malonyl-CoA by acetyl-CoA carboxylase, and acetoacetyl-CoA is synthesized from acetyl-CoA and malonyl CoA by acetoacetvl-CoA synthetase (see FIGS. 7 (steps E and F) and FIG. 9). Also provided herein are non-naturally occurring eukaryotic organisms comprising at least one exogenous nucleic acid encoding an enzyme or protein, wherein the enzyme or protein converts the substrates and products of a 1 ,3-BDO pathway, such as shown in FIG. 7. [001871 In certain embodiments, (1) the acetyl-CoA pathway comprises: 2A, 2B, 2C, 2D, 2E, 2F, 2G, 2K, 2L, 3H, 31 or 3J, or any combination of 2A, 2B, 2C, 2D, 2E, 2F, 2G, 3H. 3I and 3J, thereof; and (2) the 1,3-13DO pathway comprises 7E, 7F, 413, 4C, 4D, 4E, 4F, 4G, 4H, 41, 4J, 4K, 4L, 4M, 4N or 40, or any combination of 7E, 7F, 4B, 4C, 4D, 4E, 4F, 4G, 414. 4I, 4J. 4K, 4L, 4M, 4N and 40 thereof; wherein 7E is acetvl-CoA carboxylase; wherein 7 is an acetoacetyl CoA synthase. In one embodiment, the 1,3-BDO pathway comprises 7E. In one embodiment, the 1,3-13DO pathway comprises 7B. -92- [001881 Exemplary sets of 1,3-BDO pathway enzymes to convert acetyl-CoA to 1,3-BDO, according to FIGS, 4 and 7, include YE, 7E, 4E, 4F and 4G; 7E, 7F, 413 and 4D; 7E, 7F, 4E, 4C and 4D; 7E, 7F, 4H and 4J; 7E, 7F, 4H, 41 and 4G; 7E, 7F, 4H, 4M, 4N and 4G; 7E, 7F, 4K, 40, 4N and 4G; or 7E, 7F, 4K, 4L, 4F and 4G. [001891 In one embodiment., the 1,3-13DO pathway comprises 7E, 7F, 4E, 4F and 4G. In another embodiment, the 1 ,3-BDO pathway comprises 7E, 7F, 4B and 4D. In other embodiments, the 1,3-BDO pathway comprises 7E. 7F, 4E, 4C and 4D. In some embodiments,. the 1,343DO pathway comprises 7E, 7F, 4H and 4J. In other embodiments, the 1,3-BDO pathway comprises 7E, 7F, 4H, 41 and 4G. In certain embodiments, the 1,3-BDO pathway comprises 7E, 7F, 4H, 4M, 4N and 4G. In another embodiment, the 1,3-13DO pathway comprises 7E, 7F, 4K. 40,.' 4N and 4G. In yet another embodiment, the 1.3-BDO pathway comprises 7E, 7F, 4K, 4L, 4F and 4G. [00190] In certain embodiments, (1) the acetyl-CoA pathway comprises (i) 2A, 2B and 2D; (ii) 2A, 2C and 2D; (iii) 2A, 213, 2C and 2D; (iv) 2A, 21B, 2E and 2F; (v) 2A, 2C, 2E and 2F; (vi) 2A, 213, 2C, 2E and 2F; (vii) 2A, 213, 2E, 2K and 2L; (viii) 2A, 2C, 2E, 2K and 2L or (ix) 2A, 213, 2C, 2E, 2K and 2L, and wherein the acetyl-CoA pathway optionally further comprises 2G, 3H-, 31, 3J, or any combination thereof; and (2) the 1,3-BDO pathway comprises (i) 7E, 7F. 4E. 4F and 4G; (ii) 7E, 7F, 413 and 41); (iii) 7E, YE, 4E, 4C and 4D; (iv) 7E, 7F, 41H and 4J; (v) 7E, 7, 41H 4-I and 4G; (vi) 7E, 7F, 4H, 4M, 4N and IG; (vii) 7E, 7F, 4K, 40, 4N and 4G; or (viii) YE, 7F, 4K, 4L, 4F and 4G. [001911 In some embodiments, (1) the acetyi-CoA pathway comprises 2A, 2B and 2D; and (2) the 1,3-BDO pathway comprises (i) 7E, 7F, 4E, 4F and 4G; (ii) 7E, 7F, 4B and 4D; (iii) 7E, 7F, 4E, 4C and 4D; (iv) 7E, YF, 414 and 4J; (v) 7E, 7, 411, 41 and 4G; (vi) 7E, 7F, 4H, 4M, 4N and 4G; (vii) 7E, 7F, 4K, 40, 4N and 4G; or (viii) 7E, 7F, 4K, 4L, 4F and 4G. In some embodiments, the acetyl-CoA pathway comprises 2A, 213 and 2D. and the 1,3-BDO pathway comprises 7E, 7F, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises 2A, 2B and 2D, and the 1,3-BDO pathway comprises 7E, 7F, 413 and 4D. In one embodiment, the acetyl-CoA pathway comprises 2A, 213 and 2D, and the 1,3-BDO pathway comprises 7E, 7F, 4E, 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises 2A, 213 and 2D, and -93the 1.3-BDO pathway comprises 7E, 7F, 4H and 4J. In other embodiments, the acetyl-CoA pathway comprises2A, 2B and 21), and the 1,3-BDO pathway comprises E, 7F, 4H, 41 and 4(i. In certain embodiments, the acetyl-CoA pathway comprises 2A, 2E and 2D, and the 1,3-EDO pathway comprises 7 E, 7 F, 41-, 4M, 4N and 4G. In another embodiment, the acetyl-CoA pathway comprises 2A, 2B and 2D, and the 1 ,3-BDO pathway comprises 7E, 7F, 4K, 40, 4N and 4G, In vet another embodiment, the acetyl-CoA pathway comprises 2A, 2B and 2D, and the 1,3-BDO pathway comprises 7E, 7F, 4K, 4L, 4F and 4(i. In certain embodiments, the acetyl CoA pathway optionally further comprises 2G, 3H, 31, 3J, or any combination thereof In some embodi rents, the non-natural ly occurring eukaryotic organism comprises exogenous nucleic acids, wherein each of the exogenous nucleic acids encodes a different acetyl-CoA pathway or 1,3-BDO pathway enzyme. [00192] In other embodiments, (1) the acetyl-CoA pathway comprises 2A, 2( and 2D; and (2) the 1,3-EDO pathway comprises (i) 7E, 7F, 4E, 4F and 4G; (ii) 7E, 7F, 4B and 4D; (iii) 7E, YE, 4E, 4C and 4D; (iv) 7E, 7F, 4H and 4J; (v) 7E, 7F, 4H, 41 and 4G; (vi) 7E, 7F, 4H, 41, 4N and 4G; (vii) 7E, 7F, 4K, 40, 4N and 4G; or (viii) 7E, 7F, 4K, 4L, 4F and 4G. In some embodiments, the acetyl-CoA pathway comprises 2A, 2C and 2D, and the 1,3-BDO pathway comprises 7E, 7, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises 2A. 2C and 2D. and the 1,3-BDO pathway comprises 7E, 7F. 413 and 4D. In one embodiment, the acetyl-CoA pathway comprises 2A, 2C and 2D, and the 1,3-131) pathway comprises 7E, 7F, 4E, 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises 2A, 2C and 2D, and the 1,3-BDO pathway comprises 7E, 7F, 41-1 and 4J. In other embodiments, the acetyl-CoA pathway comprises 2A, 2C and 2D, and the I,3-BDO pathway comprises 7E, 7, 4H, 41 and 4G. In certain embodiments, the acetyl-CoA pathway comprises 2A, 2C and 2D, and the 1,3-BDO pathway comprises 7E, 7, 41-1, 4M, 4N and 4G. In another embodiment, the acetyl-CoA pathway comprises 2A. 2C and 2D, and the 1,3-BDO pathway comprises 7E, 7F, 4K, 40, 4N and 4. In vet another embodiment, the acetvl-CoA pathway comprises 2A, 2C and 2D, and the 1,3-BDO pathway comprises 7E, 7F, 4K. 4L. 4F and 4G. In certain embodiments, the acetyl CoA pathway optionally further comprises 2G, 31-1, 31, 3J, or any combination thereof. In some embodiments, the non-naturally occurring eukaryotic organism comprises exogenous nucleic -94acids, wherein each of the exogenous nucleic acids encodes a different acetyl-CoA pathway or 1,3-13DO pathway enzyme. [00193] In other embodiments, (1) the acetyl-CoA pathway comprises 2A, 213, 2C and 2D; and (2) the 1,3-BDO pathway comprises (i) 7E, 7F, 4E, 4F and 4G; (ii) 71E, 7F, 4B and 4D; (iii) 7E, 7F, 4E, 4C and 4D; (iv) 7E, 7E, 4H and 4J; (v) 7E, 7F, 411, 41 and 4G; (vi) 7E, 7E, 41, 4M, 4N and 4G; (vii) 7E, 7F, 4K, 40, 4N and 4G; or (viii) 71E, 7F, 4K, 4L, 41 and 4G. In some embodiments, the acetyl-CoA pathway comprises 2A, 213, 2C and 2D, and the 1.3-BDO pathway comprises 7E, 7E, 4E, 4E and 4G. In other embodiments, the acetyl-CoA pathway comprises 2A, 2B, 2C and 2D, and the 1,3-BDO pathway comprises 71E, 7, 4B and 4D. In one embodiment, the acetyl-CoA pathway comprises 2A, 213, 2C and 2), and the 1,3-43DO pathway comprises 7E, 7F, 4E, 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises 2A, 213, 2C and 2D, and the 1,3-BDO pathway comprises 7E, 7F, 411 and 4J. In other embodiments, the acetyl-CoA pathway comprises 2A, 2B, 2C and 2D, and the 1,3-13DO pathway comprises 7E, 7, 41-1, 41 and 4G. In certain embodiments, the acetyl-CoA pathway comprises 2A, 2B, 2C and 2D, and the 1,3-BDO pathway comprises 7E, 7F, 4H, 4M, 4N and 4G. In another embodiment, the acetyl-CoA pathway comprises 2A, 213, 2C and 2D. and the 1.3-EDO pathway comprises 7E, 7F, 4K, 40, 4N and 4(i. In yet another embodiment, the acetyl-CoA pathway comprises 2A, 2B. 2C and 2D, and the 1,3-BDO pathway comprises 7E, 7F, 4K, 4L, 4F and 4G. In certain embodiments, the acetyl-CoA pathway optionally further comprises 2G, 31-1, 31, 3], or any combination thereof. In some embodiments, the non-naturally occurring eukaryotic organism comprises exogenous nucleic acids, wherein each of the exogenous nucleic acids encodes a different acetyl-CoA pathway or 1,3-BDO pathway enzyme. [001941 In other embodiments, (1) the acetyl-CoA pathway comprises 2A, 2B, 2E and 2F; and (2) the 1,3-BDO pathway comprises (i) 7E, 7E, 4E, 4F and 4G; (ii) 7E, 7F, 4B and ID (iii) 7E, YE, 41E, 4C and 41); (iv) 7E, 7F, 41-1 and 4.; (v) 7E, 7F, 41-, 41 and 4G; (vi) 7E, 7F, 41, 4M, 4N and 4G; (vii) 7E, 7F, 4K. 40. 4N and 4G; or (viii) YE, 7F, 4K, 4L. 4F and 4G. In some embodiments, the acetyl-CoA pathway comprises 2A, 213, 2E and 21F, and the 1,3-BDO pathway comprises 7E, 7E, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises 2A, 2B 21E and 2F, and the 1,3-EDO pathway comprises 7E, 7F, 4B and 4D. In one -95embodiment, the acetyl-CoA pathway comprises 2A, 2B, 2E and 2F, and the 1,3-BDO pathway comprises 7E, 7, 4E, 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises 2A, 2B, 2E and 2F, and the I,3-BDO pathway comprises 7E, 7F, 4H and 4i. In other embodiments, the acetyl-CoA pathway comprises 2A, 2B, 2E and 2F, and the 1,3-BDO pathway comprises 7E, 7F, 4H, 41 and 4G. In certain embodiments, the acetyl-CoA pathway comprises 2A,2B, 2E and 2F, and the I,3-BDO pathway comprises 7E, YF, 41, 4M, 4N and 4G. In another embodiment, the acetyl-CoA pathway comprises 2A, 2, 2E and 2F, and the I,3-BDO pathway comprises 7E, 7F, 4K, 40, 4N and 4G. In yet another embodiment, the acetyl-CoA pathway comprises 2A, 2B, 2E and 2F, and the ],3-D() pathway comprises 7E, 7, 4K, 4L., 4F and 4G. In certain embodiments, the acetyl-CoA pathway optionally further comprises 2G, 3H, 31, 3J, or any combination thereof. In some embodiments, the non-naturally occurring eukaryotic organism comprises exogenous nucleic acids, wherein each of the exogenous nucleic acids encodes a different acetyl-CoA pathway or 1,3-BDO pathway enzyme. [001951 In other embodiments, (1) the acetyl-CoA pathway comprises 2A, 2C, 2E and 2F; and (2) the 1,3-BDO pathway comprises (i) 7E, 7F, 4E, 4F and 4G; (ii) 7E, YF, 4B and 4D; (iii) 7E, YE, 4E, 4C and 4D- (iv) 7E, 7F, 4H and 4J- (v) 7E, 7F, 4H, 41 and 4G; (vi) 7E, 7F, 4H, 4M, 4N and 4G; (vii) 7E, YE, 4K, 40, 4N and 4G; or (viii) 7E, YE, 4K, 4L, 4F and 4G. In some embodiments, the acetyl-CoA pathway comprises 2A, 2C, 2E and 2F. and the 1,3-BDO pathway comprises 7E, 7, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises 2A, 2C, 2E and 2F, and the 1,3-BDO pathway comprises 7E, 7F, 4B and 4D. In one embodiment, the acetyl-CoA pathway comprises 2A, 2C, 2E and 2E, and the 1,3-BDO pathway comprises 7E, 7F, 4E, 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises 2A, 2C, 2E and 2, and the 1,3-EDO pathway comprises 7E, 7F, 411 and 4J. In other embodiments, the acetyl-CoA pathway comprises 2A, 2C, 2E and 2E, and the 1,3-13DO pathway comprises 7E, 7F, 4H. 4I and 4G. In certain embodiments, the acetyl-CoA pathway comprises 2A, 2C, 2E and 2F, and the I,3-BDO pathway comprises 7E, YF, 411, 4M, 4N and 4G. In another embodiment, the acetyl-CoA pathway comprises 2A, 2C, 2E and 2F. and the 1,3-EDO pathway comprises YE, F, 4K, 40, 4N4 and 4G. In yet another embodiment, the acetyl-CoA pathway comprises 2A, 2C, 2E and 2F, and the 1,3-BDO pathway comprises 7E, 7F, 4K, 4L, 4F and 4G. In certain embodiments, the acetyl-CoA pathway optionally further comprises 2G, 3H, -96- 31, 3J, or any combination thereof. In some embodiments, the non-naturally occurring eukaryotic organism comprises exogenous nucleic acids, wherein each of the exogenous nucleic acids encodes a different acetyl-CoA pathway or 1,3-BDO pathway enzyme. [001961 In other embodiments, (1) the acetyl-CoA pathway comprises 2A, 2B, 2C, 2E and 2F; and (2) the I ,3-BDO pathway comprises (i) 7E, 7F, 4E, 4F and 4G; (ii) 7E, 7F, 4B and 4D; (iii) 7E, 7F, 4E, 4C and 4D; (iv) 7E, 7F, 4H and 4J; (v) 7E, 7F, 4H, 41 and 4G; (vi) 7E, 7F, 4H, 4M, 4N and 4G; (vii) 7E, 7F, 4K, 40, 4N and 4G or (viii) 7E, 7F, 4K, 4L, 4F and 4G. In some embodiments, the acetyl-CoA pathway comprises 2A, 213, 2C, 2E and 2, and the 1,3-13DO pathway comprises 7E, 7F, 4E, 411 and 4G. In other embodiments, the acetyl-CoA pathway comprises 2A, 213, 2C, 2E and 2F, and the 1,3-BDO pathway comprises 7E, 7F, 413 and 41). In one embodiment, the acetyl-CoA pathway comprises 2A, 2B. 2C, 2E and 2F, and the 1,3-BDO pathway comprises 7E, 7F, 4E, 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises 2A, 2B, 2C, 2E and 2F, and the 1,3-BDO pathway comprises 7E, 7F, 4H and 4J. In other embodiments, the acetyl-CoA pathway comprises 2A, 2B, 2C, 2E and 2F, and the 1,3-BDO pathway comprises 7E, 711, 4H, 41 and 4G. In certain embodiments, the acetyl-CoA pathway comprises 2A, 213, 2C, 21E and 2F, and the 1.3-BDO pathway comprises 7E, 7F, 4-1, 44M, 4N and 4G. In another embodiment, the acetyl-CoA pathway comprises 2A, 213, 2C, 21E and 21, and the 1,3-BDO pathway comprises 7E, 7F, 4K. 40, 4N and 4G. In yet another embodiment, the acetyl-CoA pathway comprises 2A, 2132C, 2E and 2F, and the I,3-[3DO pathway comprises 7E, 7F, 4K, 4L, 4F and 4G. In certain embodiments, the acetyl-CoA pathway optionally further comprises 2G, 3H, 31, 3J, or any combination thereof. In some embodiments, the non-naturally occurring eukaryotic organism comprises exogenous nucleic acids, wherein each of the exogenous nucleic acids encodes a different acetyl-CoA pathway or I,3-BDO pathway enzyme. [001971 In some embodiments, (1) the acetyl-CoA pathway comprises 2A, 213, 2E. 2K and 2L; and (2) the 1,3-3DO pathway comprises (i) 7E, 7, 4E, 41 and 4G; (ii) 7E, 71, 4B and 41); (iii) 71, 7F, 4E, 4C and 4D; (iv) 7E, 7F, 4H and 4J; (v) 7E, 7F, 4H, 41 and 4G: (vi) 7E, 7F, 4H, 4M, 4N and 46; (vii) 7E, 7F, 4K, 40, 4N and 4G; or (vii) 7E, 7F, 4K, 4L, 4F and 4G. In some embodiments, the acetyl-CoA pathway comprises 2A, 213, 2E, 2K and 2L, and the I,3-BDO pathway comprises 7E, 71, 4E, 4F and 4G. In other embodiments, the acetyi-CoA pathway -97comprises 2A, 2B, 2E, 2K and 2L, and the 1,3-BDO pathway comprises 7E, 7F, 4B and 4D. In one embodimen[, the acetyl-CoA pathway comprises 2A, 21,.2E, 2K and 2L, and the 1,3-3DO pathway comprises 7E, 7F, 4E, 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises 2A, 213, i2 K and 2L, and the 1,3-BDO pathway comprises 7E, 7F, 41 and 4J. In other embodiments, the acetyl-CoA pathway comprises 2A, 2B, 2E, 2K and 2L, and the 1,3 BDO pathway comprises 7E, 7, 41-1, 41 and 4G. In certain embodiments, the acetyl-CoA pathway comprises 2A, 23, 2E, 2K and 2L, and the 1,3-BDO pathway comprises 7E, 7, 4H, 4M. 4N and 4G. In another embodiment, the acetyl-CoA pathway comprises 2A, 213, 2E, 2K and 2L, and the 1,3-BDO pathway comprises 7E, 7, 4K, 40, 4N and 4G. In yet another embodiment. the acetyl-CoA pathway comprises 2A, 213, 2E, 2K and 2L and the 1,3-BDO pathway comprises 7E, 7F, 4K, 4L, 4F and 4G. In certain embodiments, the acetyl-CoA pathway optionally further comprises 2G, 3H, 31, 3J, or any combination thereof. In some embodiments, the non-naturally occurring eukaryotic organism comprises exogenous nucleic acids, wherein each of the exogenous nucleic acids encodes a different acetyl-CoA pathway or 1,3-BDO pathway enzyme. [001981 In some embodiments, (1) the acetyl-CoA pathway comprises 2A, 2C, 2E, 2K and 2L; and (2) the 1,3-BDO pathway comprises (i) 7E, 7F, 4E, 4F and 4G; (ii) YE, F, 413 and 4D; (iii) 7E, 7F, 4E, 4C and 4D; (iv) 7E. 7F, 4H and 4J; (v) 7E, 7F, 41H, 41 and 4G; (vi) 7E, 7, 4H, 4M, 4N and 4G; (vii) 7E, 7F, 4K, 40, 4N and 4G; or (viii) 7E, 7F, 4K, 4L, 4F and 4G. In some embodiments, the acetyl-CoA pathway comprises 2A, 2B, 2E, 2K and 2L, and the 1,3-BDO pathway comprises 7E, 7F, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises 2A, 213, 2E, 2K and 2L, and the 1,3-BDO pathway comprises 7E, 7F, 4B and 4D. In one embodiment, the acetyl-CoA pathway comprises 2A, 2C, 2E, 2K and 2L, and the 1,3-BDO pathway comprises 7E, 7, 4E, 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises 2A, 2C, 2E, 2K and 2L, and the 1,3-BDO pathway comprises 7E. 7F, 4H and 4J. In other embodiments, the acetyl-CoA pathway comprises 2A, 2C, 2E, 2K and 2L, and the 1,3 BDO pathway comprises 7E, 7F, 4H. 4I1 and 4G. In certain embodiments, the acetyl-CoA pathway comprises 2A, 2C, 21E, 2K and 21L, and the 1,3-BDO pathway comprises 7E, 7F, 41-, 4M, 4N and 4G. In another embodiment, the acetyl-CoA pathway comprises 2A, 2C, 2E, 2K and 2L, and the 1,3-BDO pathway comprises 7E, 7F, 4K, 40, 4N and 4G. In yet another -98embodiment. the acetyl-CoA pathway comprises 2A, 2C, 2E, 2K and 2L and the 1,3-BDO pathway comprises 7E, 7F, 4K, 4L, 4F and 4G. In certain embodiments, the acetyl-CoA pathway optionally further comprises 2G, 3H, 3I, 3J, or any combination thereof. In some embodiments, the non-naturally occurring eukaryotic organism comprises exogenous nucleic acids, wherein each of the exogenous nucleic acids encodes a different acetyl-CoA pathway or 1,3-BDO pathway enzyme. [001991 In some embodiments, (1) the acetyl-CoA pathway comprises 2A, 213, 2C, 2E, 2K and 2L; and (2) the ],3-BD() pathway comprises (i) 7E, 7F, 4E, 4F and 4G; (ii) 7E, 7F, 413 and 41); (iii) 7E, 7F, 4E, 4C and 4D; (iv) 7E, 7F, 4H and 4J; (v) 7E, 7F, 41, 41 and 4G; (vi) 7E, 7F, 4H, 4M, 4N and 4G; (vii) 7E, 7F, 4K, 40, 4N and 4G; or (viii) 7E-, 7F, 4K, 4L, 4F and 4G. In some embodiments, the acetyl-CoA pathway comprises 2A, 2B, 2C, 2E, 2K and 2L and the 1,3-BDO pathway comprises 7E, 7F, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises 2A, 213, 2C, 2E, 2K and 2L, and the 1,3-BDO pathway comprises 7E, 7F, 4B and 4D. In one embodiment, the acetyl-CoA pathway comprises 2A, 2B 2C, 2E, 2K and 2L, and the 1,3 BDO pathway comprises 71E, 7F, 4E, 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises 2A, 2B, 2C, 2E, 2K and 2L, and the 1,3-BDO pathway comprises 7E, 7F, 4H and 4J. In other embodiments, the acetyl-CoA pathway comprises 2A, 213, 2C, 21E, 2K and 2L, and the 1,3-13DO pathway comprises 7E, 7F, 41H, 41 and 4G. In certain embodiments, the acetyl CoA pathway comprises A, 213, 2C, 2E, 2K and 2L, and the 1,3-BD() pathway comprises 7E, 7F, 41H, 4M 4N and 4G. In another embodiment, the acetyl-CoA pathway comprises 2A, 213, 2C 2E, 21K and 2L, and the 1,3-BDO pathway comprises 7E, 7F, 4K, 40, 4N and 4G. In vet another embodiment, the acetyl-CoA pathway comprises 2A, 213, 2C, 2E, 2K and 2L, and the 1,3-BDO pathway comprises 7E, 7F, 4K, 41, 4F and 4G. In certain embodiments, the acetyl CoA pathway optionally further comprises 2G, 3H, 3I, 3J, or any combination thereof. In sone embodiments, the non-naturally occurring eukaryotic organism comprises exogenous nucleic acids, wherein each of the exogenous nucleic acids encodes a different acetyl-CoA pathway or 1,3-BDO pathway enzyme. [002001 In certain embodiments, (1) the acetyl-CoA pathway comprises 5A, 51B, 5C, 5D 5E, 5F, 5G, 51, 51, 5J or any combination of 5A, 5B, 5C, 5D, 5E, 5F, 5G, 51H, 51 and 5J thereof, -99wherein 5A is a pyruvate oxidase (acetate forming); 5B is an acetyl-CoA synthetase, ligase or transferase; 5C is an acetate kinase; 51) is a phosphotransacetylase; 5E is a pyruvate decarboxylase; 5F is an acetaldehyde dehydrogenase; 5G is a pyruvate oxidase (acetvl-phosphate forming); 51-1 is a pyruvate dehydrogenase, pyruvate:ferredoxin oxidoreductase or pyruvate formate lyase; 5I acetaldehyde dehydrogenase (acylating); and 5J is a threonine aldolase; and (2) the 1,3-BDO pathway comprises 7E, 7F, 4B, 4C, 4D, 4E, 4F, 4G, 4H, 41, 43, 4K, 4L, 4M, 4N or 40, or any combination of 7E, 71, 43, 4C, 4D, 41E, 4F, 4G, 41-1, 41, 4., 4K, 4L, 4M, 4N and 40 thereof; wherein 7E, 7F is an acetoacetyl-CoA thiolase; wherein 4B is an acetoacetyl-CoA reductase (CoA-dependent, alcohol forming); wherein 4C is a 3-oxobutyraldehyde reductase (aldehyde reducing); wherein 4D is a 4-hydroxy,2-butanone reductase; wherein 4E is an acetoacetyl-CoA reductase (CoA-dependent, aldehyde forming); wherein 4F is a 3 oxobutyraldehyde reductase (ketone reducing); wherein 4G is a 3-hydroxybutyraldehyde reductase; wherein 41-1 is an acetoacetyl-CoA reductase (ketone reducing); wherein 41 is a 3 hydroxybutyryl-CoA reductase aldehydee forming); wherein 4J is a 3-hvdroxybutyryl-CoA reductase (alcohol forming); wherein 4K is an acetoacetyl-Co-A transferase, an acetoacetyl-CoA hydrolase, an acetoacetyl-CoA synthetase, or a phosphotransacetoacetylase and acetoacetate kinase; wherein 41L is an acetoacetate reductase; wherein 4M is a 3-hydroxybutyryl-CoA transferase, hydrolase, or synthetase; wherein 4N is a 3-hydroxybutyrate reductase; and wherein 40 is a 3-hydroxybutyrate dehydrogenase. In certain embodiments, 5B is an acetyl-CoA synthetase. In another embodiment, 5B is an acetyl-CoA ligase. In other embodiments, 5B is an acetyl-CoA transferase. In some embodiments, 5H is a pyruvate dehydrogenase. In other embodiments, 511 is a pyruvate:ferredoxin oxidoreductase. In yet other embodiments, 5H is a pyruvate formate lyase. In certain embodiments, 4K is an acetoacetyl-CoA transferase. In other embodiments, 4K is an acetoacetyl-CoA hydrolase. In some embodiments, 4K is an acetoacetyl CoA synthetase. In other embodiments, 4K is a phosphotransacetoacetylase and acetoacetate kinase. In certain embodiments, 4M is a 3-hydroxybutyryl-CoA transferase. In some embodiments, 4M is a 3-hydroxybutyryl-CoA, hydrolase. In yet other embodiments, 4M is a 3 hydroxybutyryl-CoA synthetase. 1002011 In some embodiments, the acetyl-CoA pathway is an acetyl-CoA pathway depicted in FIG. 5, and the 1,3-BDO pathway is a i,3-BDO path way depicted in FIGS. 4 and/or 7. -100- Exemplary sets of acetyl-CoA pathway enzymes, according to FIG. 5, are 5A and 5B; 5A, 5C and 5D; 5G and 5D; 5E, 5F, SC and 5); 5J and 51; 5., 5F and 5B; and 51-I. Exemplary sets of 1 ,3-BDO pathway enzymes to convert acetyl-CoA to 1,3-BDO, according to FIGS. 4 and 7, include 7E, 7F, 4E, 4F and 4G; 7E, 7F, 4B and 4D; 7E YF, 4E, 4C and 4D; 7E, 7F, 411 and 4J; 7T, 7F, 4H, 41 and 4G; 7E, 7F, 4H, 4M, 4N and 4G; 7E, 7F, 4K, 40, 4N and 4G; or 7E, 7F, 4K, 4L, 4F and 4G. [002021 In some embodiments, (1) the acetyl-CoA pathway comprises (i) 5A and 5B; (ii) 5A, 5C and 5D; (iii) 5E, 5F, 5C and 5); (iv) 5G and 5); (v) 5i and 5I; (vi) 5J, 5F and 5B; or (vii) 5H; and (2) the 1.,3-BDO pathway comprises (i) 7E, 7F, 4E, 4F and 4G; (ii) 7E, 7F. 4B and 4D; (iii) 7E, YF, 4E, 4C and 4D; (iv) 7E, 7F, 41-1 and 4.; (v) 7E, 7F, 41-, 41 and 4G; (vi) 7E, 7, 41-, 4M, 4N and 4G; (vii) 7E, 7F, 4K. 40, IN and 4G; or (viii) 7E, 7F, 4K, 4L, 4F and 4G. 1002031 In some embodiments, the acetyl-CoA pathway comprises 5A and 5B; and the 1,3 BDO pathway comprises 7E, 7F, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises 5A and 5B; and the 1,3-BDO pathway comprises 7E, 7F, 4B and 4D. In sonic embodiments, the acetyl-CoA pathway comprises 5A and 5B; and the 1,3-BDO pathway comprises 7E, 7F, 4E, 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises 5A and 5B: and the 1,3-BDO pathway comprises 7E. 7F7, 4-H and 4J. In some embodiments, the acety-CoA pathway comprises SA and 5B; and the 1,3-3DO pathway comprises YE, 7F, 4H1-, 41 and 4G. In some embodiments, the acetyl-CoA pathway comprises 5A and 5B; and the 1.3-BDO pathway comprises 7 E, 7 F, 41-, 4M, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises 5A and 5B; and the 1,3-BDO pathway comprises 7E, 71, 4K, 40, 4-N and 4G. In some embodiments, the acetyl-CoA pathway comprises 5A and 5B; and the 1,3-BDO pathway comprises 7E, 7F, 4K, 4L, 4F and 4G. [002041 In some embodiments, the acetyl-CoA pathway comprises 5A, 5C and SD; and the 1,3-BDO pathway comprises 7E, 7F, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises 5A, 5C and 5D; and the 1,3-BDO pathway comprises 7E, F, 413 and 4D. In some embodiments, the acetyl-CoA pathway comprises 5A, 5C and SD; and the 1,3-BDO pathway comprises 7E, 7F, 4E, 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises 5A, 5C and 5D; and the 1,3-BDO pathway comprises 7E, 7F, 4H and 4J. In some -101embodiments, the acetyl-CoA pathway comprises 5A, SC and 5D; and the 1,3-BDO pathway comprises 7E, 7, 4H, 41 and 4G. In some embodiments, the acetyl-CoA pathway comprises 5A, 5C and 5D; and the 1,3-BDO pathway comprises 7E, 7F, 4H, 4M, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises 5A, 5C and 5D; and the 1,3-BDO pathway comprises 7E, 7F, 4K, 40, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises 5A, SC and 5D; and the I ,3-BDO pathway comprises 7 E, 7F, 4K, 41, 4F and 4G, [002051 In some embodiments, the acetyl-CoA pathway comprises 5E, 5F, 5C and SD; and the I,3-13D pathway comprises 7E, 7F, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises 5E, 5F, 5C and SD: and the 1,3-BDO pathway comprises 47 7F, IB and 4D. In some embodiments, the acetVl-CoA pathway comprises 5E, 5F, 5C and 5D; and the 1,3-BD) pathway comprises 7E, 7F. 4E, 4C and 41D. In some embodiments, the acetyl-CoA pathway comprises 5E, 5F, SC and 5D; and the I ,3-BDO pathway comprises YE, 7F, 41-1 and 4J. In some embodiments, the acetyl-CoA pathway comprises 5E, 5F, 5C and 5D; and the 1,3-BDO pathway comprises 7E, 7F, 41-1, 41 and 4G. In some embodiments, the acetyl-CoA pathway comprises 5E, 5F, 5C and 5D; and the 1,3-BDO pathway comprises 7E, 7F, 4H, 4M, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises 5E, 5F, SC and 5D; and the 1.3-BDO pathway comprises 7E, 7F, 4K, 40, 4N and 4G. In some embodiments, the acetvl-CoA pathway comprises 5E, 5F, 5C and 5D; and the 1,3-BDO pathway comprises 7E, 7F, 4K., 4L., 4F and 4G. [002061 In some embodiments, the acetyi-CoA pathway comprises 5G and SD; and the 1,3 BDO pathway comprises 7E, 7F, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises 5G and 5D; and the 1,3-BDO pathway comprises 7E, 7F, 4B and 4D. In some embodiments, the acetyl-CoA pathway comprises 5G and 5D; and the 1,3-BDO pathway comprises 7E, 7F, 4E, 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises 5G and 5D and the 1.,3-BDO pathway comprises -7E. 7F, 4H and 4J. In some embodiments, the acetyl-CoA pathway comprises 5G and 5D; and the I,3-BD) pathway comprises 7E, 7F, 4[H, 41 and 4G. In some embodiments,. the acetyl-CoA pathway comprises 5G and 5D; and the 1,3 BDO pathway comprises 7E, 7F, 4[H, 4M, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises 5G and 5D; and the 1,3-BDO pathway comprises 7E, YF, 4K, 40, 4N and -102- 4G. In some embodiments, the acetyl-CoA pathway comprises SG and 5D; and the 1,3-BDO pathway comprises 7E, 7F, 4K, 4L, 4F and 4G. [00207] In some embodiments, the acetyl-CoA pathway comprises 5J and 51; and the I ,3-BDO pathway comprises 7E, 7F, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises 5J and 51; and the 1,3-BDO pathway comprises 7E, 7F, 413 and 4D. In some embodiments, the acetyl-CoA pathway comprises 5J and 5I; and the 1,3-BDO pathway comprises 7E, 7F, 4E, 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises 5J and 5I; and the I,3-BDO pathway comprises YE, 7, 41-i and 4.1. 1n some embodiments, the acetyl-CoA pathway comprises 5J and 5I; and the 1,3-BDO pathway comprises 7E, 7F, 4H, 4I and 4G. In some embodiments, the acetyl-CoA pathway comprises 5. and 5I; and the 1,3-BDO pathway comprises 7E, 7F. 4-H, 4M, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises 5J and 5I; and the I,3-BDO pathway comprises 7E, 7F, 4K, 40, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises 5J and 5I; and the 1 ,3-BDO pathway comprises 7E, 7F, 4K, 4L, 4F and 4G. [00208] In some embodiments, the acetyl-CoA pathway comprises 5J, 5F and 5B; and the 1,3 BDO pathway comprises 7E, 7F, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises 5J, 5F and 5B; and the 1,3-BDO pathway comprises 7E, 7, 4B and 4D. In some embodiments, the acetyl-CoA pathway comprises 5.J, 5F and 5B; and the I,3-BDO pathway comprises 7E, 7F, 4E, 4C and 44D. In some embodiments, the acetyl-CoA pathway comprises 5J, 5F and 5B; and the 1,3-BDO pathway comprises 7E, 7F, 41 and 4J. In some embodiments, the acetyl-CoA pathway comprises 5J, 5F and 5B; and the 1,3-BDO pathway comprises 7E, 7F, 41, 41 and 4G. In some embodiments, the acetyl-CoA pathway comprises 5, 5F and 5B; and the 1,3-BDO pathway comprises 7E, 7F, 4H, 4M, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises 5J, 5F and 5B; and the 1,3-BDO pathway comprises 7E, 7F, 4K, 40, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises 5J, 5F and 5B; and the 1 ,3-BDO pathway comprises 7E, 7F, 4K, 4L, 4F and 4G. [00209] In some embodiments, the acetyl-CoA pathway comprises SH; and the 1,3-BDO pathway comprises 7E, 7F, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises 5H; and the 1 3-BDO pathway comprises 7E, 7F, 4B and 4D. In some embodiments, -103the acetyl-CoA pathway comprises 5H; and the 1,3-BDO pathway comprises 7E, 7F, 4E, 4C and 4D. In some embodiments, the acetvl-CoA pathway comprises 51-; and the 1,3-BDO pathway comprises 7E, 7F, 4H and 4J. In some embodiments, the acetyl-CoA pathway comprises 5H; and the 1,3-13DO pathway comprises 7E, 7F, 4H, 41 and 4G, In some embodiments, the acetyl CoA pathway comprises 5H; and the I,3-BDO pathway comprises 7E, 7F, 4H, 4NI, 4N and 4G. In some embodiments, the acetyi-CoA pathway comprises 5H; and the 1,3-BDO pathway comprises 7E, 71, 4K, 40, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises 5H; and the 1.3-BDO pathway comprises 7E, 7F, 4K, 4L, 4F and 4G. [002101 In certain embodiments, (1) the acetyl-CoA pathway comprises 6A, 6B, 6C, 6D or 6E, or any combination of 6A, 613, 6C, 6D and 6E thereof, wherein 6A is mitochondrial acetylearnitine transferase; 6B is a peroxisomal acetylcamitine transferase; 6C is a cytosolic acetyicarnitine transferase; 6D is a mitochondrial acetylcarnitine translocase; and 6E. is peroxisonal acetylcarnitine translocase; and (2) the 1,3-BDO pathway comprises 7E, 71, 413, 4C, 4D, 4E, 4F, 4G, 4H, 41, 4J, 4K, 4L, 4M, 4N or 40, or any combination of 71E, 71F, 413, 4C, 4D, 4E, 4F, 4G, 4H, 41, 4J, 4K, 4L, 4M, 4N and 40 thereof; wherein 71E, 7F is an acetoacetyl CoA thiolase; wherein 4B is an acetoacetyl-CoA reductase (CoA-dependent. alcohol forming); wherein 4C is a 3-oxobutyraldehyde reductase (aldehyde reducing); wherein 41) is a 4 hydroxy.2-butanone reductase; wherein 4E is an acetoacetyl-CoA reductase (CoA-dependent., aldehyde forming); wherein 4F is a 3-oxobutyraldehyde reductase (ketone reducing): wherein 4G is a 3-hydroxybutyraldehyde reductase: wherein 4H is an acetoacetyl-CoA reductase (ketone reducing); wherein 41 is a. 3-hydroxybutyryl-CoA reductase (adehyde foring); wherein 4J is a 3-hydroxybutyryl-CoA reductase (alcohol forming); wherein 4K is an acetoacetyl-CoA transferase, an acetoacetyl-CoA hydrolase, an acetoacetyl-CoA synthetase, or a phosphotransacetoacetylase and acetoacetate kinase; wherein 4L is an acetoacetate reductase; wherein 4M is a 3-hydroxybutyryl-CoA transferase, hydrolase, or synthetase; wherein 4N is a 3 hydroxybutyrate reductase; and wherein 40 is a 3-hydroxybutyrate dehydrogenase. In certain embodiments., 4K is an acetoacetyl-CoA transferase. In other embodiments, 4K is an acetoacetyl-CoA hydrolase. In some embodiments, 4K is an acetoacetyl-CoA synthetase. In other embodiments, 4K is a phosphotransacetoacetylase and acetoacetate kinase. In certain embodiments, 4M is a 3-hydroxybutyryl-CoA transferase. fn some embodiments, 4M is a 3 -104hydroxybutyryl-CoA, hydrolase. In yet other embodiments, 4M is a 3-hydroxybutyryl-CoA synthetase. [00211] In some embodiments, the acetyl-CoA pathway is an acetyl-CoA pathway depicted in FIG. 6, and the I,3-BDO pathway is a 1,3-BDO pathway depicted in FIG. 4 and/or 7. Exemplary sets of acetyl-CoA pathway enzymes, according to FIG. 6, are 6A, 6D and 6C; and 6B. 6E and 6C. Exemplary sets of 1,3-BDO pathway enzymes to convert acetyl-CoA to 1,3 BDO,. according to FIGS. 4 and 7., include 7E, 7F, 4E, 4F and 4G; 7E, 7F. 4B and 4D; 7E, 7F, 4E, 4C and 4D; 7E, 7F, 41-1 and 4J; 7E, 7F, 41], 41 and 4G; 71, 7F, 4H, 4M, 4N and 4G; 7E, 7F, 4K, 40, 4N and 4G; or 7E, 7, 41K, 4L, 4F and 4G. [002121 In one embodiment, (1) the acetyl-CoA pathway comprises (i) 6A, 6D and 6C; or (ii) 6B, 6E and 6(; and (2) the 1,3-3DO pathway comprises (i) 7E, 77, 4E, 4F and 4G; (ii) 7E, 7F, 4B and 4D; (iii) 7E, 7F, 4E, 4C and 4D; (iv) 7E, 7F, 4H and 4J; (v) 7E, 7F, 4H, 41 and 4G; (vi) 7E, 7F, 41, 4M, 4N and 4G; (vii) 7E, 7 4K, 40, 4N and 4G; or (viii) 7E. 7F, 4K, 4L, 4F and 4G. [002131 In some embodiments, the acetyl-CoA pathway comprises 6A, 6D and 6C; and the 1,3-BDO pathway comprises 7E, 7F, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises 6A, 6D and 6C; and the 1,3-3DO pathway comprises 7E, 7F, 413 and 41). In some embodiments, the acetyl-CoA pathway comprises 6A, 6D and 6C; and the 1,3-BDO pathway comprises 7E, 7F, 4E, 4C and 41). In some embodiments, the acetyl-CoA pathway comprises 6A, 6D and 6C; and the 1,3-BDO pathway comprises 7E, 7F, 4H and 4J. In some embodiments, the acetyl-CoA pathway comprises 6A, 6D and 6C; and the 1,3-BDO pathway comprises 7E, 7F, 4H, 41 and 4G. In some embodiments, the acetyl-CoA pathway comprises 6A, 6D and 6C; and the 1,3-BDO pathway comprises 7E, 7, 41-1, 4M, 4N and 4G. In sonie embodiments, the acetyl-CoA pathway comprises 6A, 61) and 6C; and the I,3-BDO pathway comprises 7E, TF, 4K, 40, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises 6A, 61) and 6C; and the 1,3-3DO pathway comprises 7E, 7F, 4K, 4L, 4F and 4G. 1002141 In some embodiments, the acetyl-CoA pathway comprises 6B, 6E and 6C; and the 1,3 BDO pathway comprises 7E, 7F, 4E, 4F and 4G. In other embodiments, the acetyl-CoA -105pathway comprises 6B, 6E and 6C; and the 1,3-BD0 pathway comprises 7E, 7F, 4B and 4D. In some embodiments, the acetyl-CoA pathway comprises 613, 6E and 6C; and the 1,3-BDO pathway comprises 7E, 7F, 4E, 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises 6B, 6E and 6C; and the 1,3-13DO pathway comprises 7E, 7F, 411 and 4J. In some embodiments, the acetyl-CoA pathway comprises 6B, 6E and 6C; and the 1,3-BDO pathway comprises 7E, 7F, 4H, 41 and 4G. In some embodiments, the acetyl-CoA pathway comprises 6B 6E and 6C; and the 1,3-BDO pathway comprises 7E, 71, 411, 4M, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises 6B, 6E and 6C; and the 1,3-BDO pathway comprises 7E, 7F, 4K, 40, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises 6B, 6E and 6C; and the 1,3-BDO pathway comprises 7E, 7F, 4K, 4L, 4F and 4G. [002151 In certain embodiments, (1) the acetyl-CoA pathway comprises IA, 10B 10C, 1OD, 10F, 10G, 101. 10J, 10K, IOL, 1GM, ION, oranycombinationof I0A, lOB, 10C, 10D, loF, lOG. 10H. 10J, 10K, IOL, 10M, ION thereof; and (2) the 1,3-BDO pathway comprises 71E (see also FIG 10, step D), 7F (see also FIG. 10, step E), 4B, 4C, 4D, 4E, 4F, 4G, 411, 41, 4J, 4K, 4L, 4M, 4N or 40, or any combination of 7E, 7F, 41, 4C, 4D, 4E, 4F, 4G, 4H, 41, 4J, 4K, 4L, 4M, 4N and 40 thereof In certain embodiments, 4K is an acetoacetyl-CoA transferase. In one embodiment, IA is a PEP carboxylase. In another embodiment, IA is a PEP carboxykinase. In an embodiment, IOF is an oxaloacetate dehydrogenase. In other embodiments, 10F is an oxaloacetate oxidoreductase. In one embodiment, 1 OK is a malonvl-CoA synthetase. In another embodiment, 10K is a malonyl-CoA transferase. In one embodiment, 10 M is a malate dehydrogenase. In another embodiment, 10M is a malate oxidoreductase, In other embodiments, ION is a pyruvate kinase. In some embodiments, I ON is a PEP phosphatase. In other embodiments, 4K is an acetoacetyl-CoA hydrolase. In sonic embodiments, 4K is an acetoacetyl-CoA synthetase. In other embodiments, 4K is a phosphotransacetoacetylase and acetoacetate kinase. In certain embodiments, 4M is a 3-hydroxybutyryl-CoA transferase. In some embodiments, 4M is a 3-hydroxybutvryl- .oA, hydrolase. In yet other embodiments, 4M is a 3-hydroxybutyryl-CoA synthetase. [002161 In some embodiments, the acetyl-CoA pathway is an acetyl-CoA pathway depicted in FIG. 10, and the 1,3-BDO pathway is a 1,3-BDO pathway depicted in FIG. 4 and/or 7. -106- Exemplary sets of acetyl-CoA pathway enzymes, according to FIG. 10, are I0A, 10B and 10C; ION, 10Ff, 1013 and 10C; 10 N, 10 L, 10M, 1013 and I C; I0A, 101B, 10G and 101); 1ON, 10H, 10B, lOG and IOD; ION, IOL, 10M, 10B, 1OG and 1OD; IDA, 1OB, 10J, 10K and 1OD; ION, 10H, 10B, IGJ, 10K and IOD; ION, 10L, 10M, 1GB, TDJ, 10K and IOD; IDA, ]DF and IOD; ION, IO, I0F and 10D; and 10N, 1OL, 10M, 1OF and I GD. Exemplary sets of 1,3-BDO pathway enzxines to convert acetyl-CoA to 1 ,3-BDO, according to FIGS. 4 and 7, include 7E, TF, 4E, 4F and 4G; TE, 7F, 4B and 41); 7E, 7F, 4E, 4C and 4D; 7E, 7, 41-1 and 43: 7E, 7F, 4Ff, 41 and 4G; 7E, 7F, 4H, 4M, 4N and 4G; 7E, 7F. 4K, 40, 4N and 4G; or 7E, 7F, 4K, 4L, 4F and 4G. [002171 In one embodiment, (1) the acetyl-CoA pathway comprises (i) IDA, 10B and 10C; (ii) ION, 10H, 10B and 10C; (iii) ION, I0L, 1DM, 10B and 10C; (iv) 10A, 10B, 10G and 101); (v) ION, 10H, 10B, lOG and IOD; (vi) ION, IOL, 10M, 10B, 1OG and IOD; (vii) IDA, 10B, iDJ, 10K and IOD; (viii) 10N, 10Ff, 101, 103, 10K and 1OD; (ix) ION, IOL, 1DM, 1DB, 10J, 10K and IOD; (x) IA, 1 OF and 10D; (xi) 10N, 10H, 1OF and iD; or (xii) ION, 1OL, 1DM, IDF and 1OD; and (2) the 1,3-BDO pathway comprises () 7E, 7F, 4E, 4F and 4G; (ii) 7E, 7F, 4B and 4D; (iii) 7E, TF, 4E, 4C and 4D; (iv) 7E, TF, F4H and 4J; (v) TE, 7F, 4H, 41 and 4G; (vi) 7E, 7F, 4H, 4M, 4N and 4G; (vii) TE, 7F, 4K. 40. 4N and 4G; or (viii) 7E, 7F, 4K, 4L. 4F and 4G. [002181 In some embodiments, the acetyl-CoA pathway comprises IDA, lOB and 10C; and the 1,3-BDO pathway comprises 7E, 7, 4E, 41 and 4G. In other embodiments, the acetyl-CoA pathway comprises IDA, 10B and 10C; and the 1.3-BDO pathway comprises 7E, 7F, 4B and 4D. in some embodiments, the acetyl-Co-A pathway comprises I0A, 1GB and 10C; and the 1,3-BDO pathway comprises 7E, 7F, 4E, 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises I GA, 1GB and 10C; and the I,3-BDO pathway comprises TE, 7F, 41-1 and 4J. In some embodiments, the acetyl-CoA pathway comprises I0A, lOB and 10C; and the 1,3-BDO pathway comprises 7E, 7F, 4H, 41 and 4G. In some embodiments, the acetyl-CoA pathway comprises IDA, 10B and 10C;: and the 1,3-3DO pathway comprises 7, TV, 4H, 4M, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises I0A, 10B and 10C: and the I.,3-BDO pathway comprises 7E, 7T, 4K, 40, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises iDA, 10B and 10C; and the i,3-BDO pathway comprises 7E, 7F, 4K, 4L, 4F and 4G. -107- [002191 In some embodiments, the acetyl-CoA pathway comprises ION, IH, lOB and IOC; and the I,3-BDO pathway comprises 71, 7F, 41E, 4F and 4G. In other embodiments, the acetyl CoA pathway comprises ION, 10H, 10B and 10C; and the 1,3-BDO pathway comprises 7E, 7F, 4B and 4D. In some embodiments, the acetyl-CoA pathway comprises ION, 101-1, 1OB and 10C; and the 1,3-BDO pathway comprises 7E, 7F, 4E, 4C and 4D. In some embodiments, the acetyl CoA pathway comprises ION, 101-1, 1GB and 10C; and the I,3-BDO pathway comprises 7 E, 7 F, 41- and 4.. In some embodiments, the acetvl-CoA pathway comprises ION, 101-1, 1013 and 1OC; and the 1,3-BDO pathway comprises 7E, 7F. 4H, 41 and 4G. In some embodiments, the acetyl CoA pathway comprises ION, 10U, 10B and 10C and the 1,3-13D) pathway comprises 7E, 7F, 4H, 4M, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises ION, 10H, lOB and I OC; and the I,3-3DO pathway comprises 7E, 7, 4K, 40, 4N and 4G, In some embodiments, the acetyl-CoA pathway comprises ION, 10H, 10B and 10C; and the 1,3-BDO pathway comprises 7 E, 7 F, 4K, 41, 4F and 4G. [002201 In some embodiments, the acetyl-CoA pathway comprises ION, 10L, 1GM, 10B and 10C; and the 1,3-BDO pathway comprises 7E, 7F, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises ION, IOL, 1GM, 1GB and 1OC; and the 1,3-BDO pathway comprises 7E, 7F, 413 and 4D. In some embodiments, the acetyl-CoA pathway comprises ION, 10L, 1GM, lOB and 1OC; and the 1,3-BDO pathway comprises 7E, 7, 4E, 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises ION, IOL, 1GM, 1013 and 10C; and the 1,3 BDO pathway comprises 7E, 7F, 4H and 4J. In some embodiments, the acetyl-CoA pathway comprises ION, 10L, 1GM, 10B and 10C; and the 1,3-BDO pathway comprises 7E, 7, 411, 41 and 4G. In some embodiments, the acetyl-CoA pathway comprises ION, IOL, 10M, 10B and IOC; and the 1,3-BDO pathway comprises 7E, 7F, 41-1, 4M, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises ION, I 1L, 1 ON1, 1013 and 10C; and the 1,3-BD0 pathway comprises 7E, 7F, 4K. 40,. 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises ION, I OL, I N, 1013 and 10C; and the 1,3-13D0 pathway comprises 7E, 7F, 4K, 4L., 4F and 4G. [002211 In some embodiments, the acetyl-CoA pathway comprises 10A, 10B, lOG and 10D; and the 1,3-BDO pathway comprises 7E, 7F, 4E, 4F and 4G. In other embodiments, the acetyl -108- CoA pathway comprises 10A, 10B, 10G and 10D; and the 1,3-BDO pathway comprises 7E, 7F, 413 and 4D. In some embodiments, the acetyl-CoA pathway comprises IGA, 10B, 10G and 101); and the 1,3-BDO pathway comprises 7E, YF, 4E, 4C and 4D. In some embodiments, the acetyl CoA pathway comprises IA, 10B, 10G and 10 D; and the 1,3-BDO pathway comprises 7E, 7F, 4H and 4J. In some embodiments, the acetyl-CoA pathway comprises I0A, 1OB, 10G and IOD; and the 1 ,3-BDO path way comprises 7T, 7F, 41-1, 41 and 4G. In some embodiments, the acetyl CoA pathway comprises 10A, 10B, 10G and 10D; and the 1,3-B3DO pathway comprises 7E, TF, 4H IM, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises IGA, lOB, 10G and 101D; and the 1,3-BDO pathway comprises 7E, 7F, 4K, 40, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises 10A, 1GB, 10G and 10D; and the 1,3-BDO pathway comprises 7E, 7, 4K, 4L, 4F and 4G. [00222] In some embodiments, the acetyl-CoA pathway comprises ION, 101-, 10B, 10G and 1OD; and the 1,3-BDO pathway comprises 7E, 7F, 4E, 4F and 4G. in other embodiments, the acetyl-CoA pathway comprises ION, 10H, 1013, 10(G and IOD; and the 1,3-BDO pathway comprises 7E, 7F, 4B and 4D. In some embodiments, the acetyl-CoA pathway comprises ION, I0H, lOB, 10G and 10D; and the 1,3-BDO pathway comprises 7E, 7F, 4E, 4C and 4D. In some embodiments, the acetvl-CoA pathway comprises ION, 101-1, 1013, 10G and 10D; and the 1,3 BDO pathway comprises 7E, 7F, 4H and 4J. In some embodiments, the acetyl-CoA pathway comprises ION, 10H, 10B, 10G and 101); and the 1,3-131) pathway comprises TE, 7, 4H, 41 and 4G. In some embodiments, the acetyl-CoA pathway comprises ION, 101-1, 10B, 10G and 10 D; and the 1,3-BDO pathway comprises YE, F, 41-1, 4, 4N and 4G. In sonic embodiments, the acetyl-CoA pathway comprises ION, 10H, 1GB, 10G and IOD; and the 1,3-BDO pathway comprises 7E, 7F, 4K, 40, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises ION, 10H, 10B, 10G and 101); and the 1,3-131) pathway comprises 7, T7, 4K, 4L, 4F and 4G. [002231 In some embodiments, the acetyl-CoA pathway comprises ON, IOL, 1GM, 1GB, 10G and 101); and the 1,3-131) pathway comprises TB, TB, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises ION, IOL, 1DM, 10B, 10G and IOD; and the 1,3-BDO pathway comprises 7 E, 7 F, 4B and 4D. In some embodiments, the acetyl-CoA pathway -109comprises ION, IOL, 10M, 1GB, 10G and 10D; and the 1,3-BDO pathway comprises 7E, 7F, 4E, 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises ION, 1OL, 10M, 10B, lOG and 10D; and the 1,3-BDO pathway comprises 7E, 7F, 4H and 4i. In some embodiments, the acetyl-CoA pathway comprises ION, 10L, 10M, 10B, 10G and lOD; and the 1,3-BDO pathway comprises 7E, 7F, 4H, 41 and 4G. In some embodiments, the acetyl-CoA pathway comprises ION, 10L, 10M, 10B, 10G and IOD; and the 1,3-BDO pathway comprises 7E, 7F, 411, 4M, 4N and 4. In some embodiments, the acetyl-CoA pathway comprises ION, IOL, 1GM, 10B, 10G and 1OD; and the 1,3-BDO pathway comprises 7E. 7F, 4K, 40, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises ION, IOL, 1GM, 1013, 1 GG and 10D; and the 1,3-BDO pathway comprises 7E. 7F, 4K, 4L, 41F and 4G. [002241 In some embodiments, the acetyl-CoA pathway comprises iA, 10B, 10J, 10K and 10 D; and the I ,3-BDO pathway comprises 7E, 71F, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises 10A, 10B, iGJ, 10K and IOD; and the I,3-BDO pathway comprises 7E, 71, 4B and 4D. In some embodiments, the acetyl-CoA pathway comprises IA, 10B, 10J, 1GK and I0D; and the 1,3-BDO pathway comprises 71E, 71, 4E, 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises iGA, 1013. 10J., iK and iGD; and the 1,3 BDO pathway comprises 7E, 7F, 4[1 and 4J. In some embodiments, the acetvl-CoA pathway comprises I0A, 1GB, IOJ, 10K and 1OD; and the 1,3-BDO pathway comprises 71E, 7F 4-H, 41 and 4G, In some embodiments, the acetyl-CoA pathway comprises IA, 10B, 1 OJ, 10K and 10D; and the 1,3-BDO pathway comprises 7E, 7F, 4H, 4N, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises IGA, 1GB, 10, 10K and IGD; and the 1,3-BDO pathway comprises 71E, 7F, 4K, 40, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises I0A, lOB, 10J, 10K and IOD; and the 1,3-BDO pathway comprises 71E, 7F, 4K, 4L, 4F and 4G. 1002251 In some embodiments, the acetyl-CoA pathway comprises ION, 10-IH, 10B, 10.1, 10K and 1OD; and the 1,3-BDO pathway comprises 7E, 7F, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises TON, 101, 10B, 10], 10K and 1OD; and the 1,3-BDO pathway comprises 7E, 7F, 4B and 4D. In some embodiments, the acetyl-CoA pathway comprises ION, 1GH, 10B, 10J, 10K and IOD; and the 1,3-BDO pathway comprises 7E, 7F, 4E, -110- 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises ION. 10H, 10B, 1OJ, 10K and 101); and the 1,3-BDO pathway comprises 7E, 7F, 4H and 4J. In some embodiments, the acetyl-CoA pathway comprises ION, 10H, 10B, 10J, 10K and IOD; and the I,3-BDO pathway comprises 7E, 7F, 41-1, 41 and 4G. In some embodiments, the acetyl-CoA pathway comprises ION, 10H, 10B, 10J, 10K and IOD; and the 1,3-BDO pathway comprises 7E, 7F, 4H, 4M, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises ION, 10H, 10B, 10J, 10K and 101); and the 1,3-131 pathway comprises 7E, 7F, 4K, 40, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises 10N, 101, 10B, IOJ, 10K and 1OD; and the 1,3-BDO pathway comprises 7E, 71, 4K, 4L, 4F and 4G. 1002261 In some embodiments, the acetyl-CoA pathway comprises ION, IOL, 1DM, 10B, 10.1, 10K and IOD; and the 1,3-BDO pathway comprises 7E, 7F, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises ION, I OL, 10M, 10B, 10J, 10K and IOD; and the 1,3-BDO pathway comprises 7E, 7F, 4B and 4D. In some embodiments, the acetyl-CoA pathway comprises ION, 10L, 10M, 1OB, 10J, 10K and 1OD; and the 1,3-BDO pathway comprises 7E, 7F, 4E, 4C and 4D. in some embodiments, the acetyl-CoA pathway comprises ION, IOL, 10M, 10B, 1OJ, 10K and 1OD; and the 1.3-BDO pathway comprises 7E, 7F, 4H and 4J. In some embodiments, the acetyl-CoA pathway comprises ION, 10L, 10M, 1013, 103, 101K and 10D; and the 1,3-13DO pathway comprises 7E. 7F, 4H, 41 and 4G. In some embodiments, the acetvl-CoA pathway comprises ION, I 1L, 10 N', 1013, 10J, 10K and 10D; and the 1,3-BDO pathway comprises 71E, 7F, 4H, 4M, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises ION, 10L, 10M, 10B, 103, 10K and 10D; and the 1,3-BDO pathway comprises 7E, 71, 4K, 40, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises ION, IOL, 1DM, 101B, 1 OJ, IOK and I GD; and the 1,3-BDO pathway comprises 7E, 7F, 4K, 4L, 4F and 4G. [002271 In some embodiments, the acetyl-CoA pathway comprises 10A, IOF and IOD; and the 1,3-BDO pathway comprises 7E, 71, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises IA, 10F and 1OD; and the 1,3-BDO pathway comprises 7E, 7F. 41B and 4D. In some embodiments, the acetyl-CoA pathway comprises I0A, 101 and 10D and the 1,3-3DO pathway comprises 7E, 7F, 4E, 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises IA, 10F and 10D; and the 1,3-BDO pathway comprises 7E, 7F, 411 and 4J. In some -111embodiments, the acetyl-CoA pathway comprises I0A, 1OF and IOD; and the 1,3-BDO pathway comprises 7E, 7F, 4W, 41 and 4G. In some embodiments, the acetyl-CoA pathway comprises IGA, IGF and 10D; and the 1,3-BDO pathway comprises 7E, 7F, 4H, 4M, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises IA, 1OF and 1OD; and the 1,3-BDO pathway comprises 7E, 7F, 4K, 40, 4N and 4G. In some enbodiments, the acetyl-CoA pathway comprises I GA, I OF and I GD; and the 1,3-BDO pathway comprises 7E, 7F, 4K, 4L, 4F and 4G. [002281 In some embodiments, the acetyl-CoA pathway comprises 1ON, IH, 1F aiid 1OD; and the I,3-BDO pathway comprises YE, 7F, 4E, 4F and 4G. In other embodiments, the acetyl CoA pathway comprises 10N, 10H, 1GF and IOD; and the 1,3-BDO pathway comprises 7E, 7, 43 and 41). In some embodiments, the acetyl-CoA pathway comprises IGN, 10H, 10F and 10D; and the 1,3-BDO pathway comprises 7E, 7F, 4E, 4C and 4D. In some embodiments, the acetyl Co-A pathway comprises I GN, 10-L, 1 OF and 10 D; and the 1,3-BDO pathway comprises 7E, 7F, 4H and 4J. In some embodiments, the acetyl-CoA pathway comprises ION, 1 OH, 1 OF and I GD; and the 1,3-BDO pathway comprises 7E, 7F, 4H, 41 and 4G, In some embodiments, the acetyl CoA pathway comprises ION, lOH, lOF and 10D; and the 1,3-BDO pathway comprises 7E, 7F, 4H, 4M, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises ION, 10H, 10F and 101D; and the 1,3-BDO pathway comprises 7E, 7F, 4K, 40, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises ION, iH, I0F and 10D; and the 1,.3-BDO pathway comprises 7E, 7F, 4K, 4L, 4F and 4G. [002291 In some embodiments, the acetyl-CoA pathway comprises ION, 1OL 10M, 10F and 1OD; and the 1,3-BDO pathway comprises 7E, 7F, 4E, 4F and 4G. In other embodiments, the acetyl-CoA pathway comprises ION, I OL IOM, I OF and I GD; and the 1,3-BDO pathway comprises 7E, 7E, 4B and 4D. In some embodiments, the acetyl-CoA pathway comprises lON, 1OL. 1GM, 1OF and 1OD; and the 1,3-BDO pathway comprises 7E, 7F. 4E, 4C and 4D. In some embodiments, the acetyl-CoA pathway comprises ION, 10L. 10M, 10F and 101) and the 1,3 BDO pathway comprises 7E, 7F, 4H and 4J. In some embodiments, the acetyl-CoA pathway comprises ION, I OL I GM, I OF and 101); and the I,3-BDO pathway comprises 7E, 7F, 41-1, 41 and 4G. In some embodiments, the acetyl-CoA pathway comprises ION, IOL. 10M, I0F and IOD; and the 1,3-BDO pathway comprises 7E, 7F, 41-, 4M, 4N and 4G. In some embodiments, -112the acetyl-CoA pathway comprises ION, IOL. 10M, 10F and IOD; and the 1,3-BDO pathway comprises 7E, 7F, 4K, 40, 4N and 4G. In some embodiments, the acetyl-CoA pathway comprises ION, 10L. iON , IF and IOD; and the 1,3-BDO pathway comprises 7E, 7F, 4K, 4L, 4F and 4G. [002301 In an additional embodiment, provided herein is a non-naturally occurring eukaryotic organism having a I,3-BDO pathway, wherein the non-naturally occurring eukaryotic organism comprises at least one exogenous nucleic acid encoding an enzyme or protein that converts a substrate to a product selected from the group consisting of acetyl-CoA to acetoacetyl-CoA (e.g., 7E, 7F); acetoacetyl-CoA to 4-hydroxy-2-butanone (e.g., 4B); 3-oxobutyraldehyde to 4-hydroxy 2-butanone (e.g., 4C); 4-hydroxy-2-butanone to 1,3-BDO (e.g., 4D); acetoacetyl-CoA to 3 oxobutyraldehyde (e.g., 4E); 3-oxobutyraldehyde to 3-hydroxybutyrldehyde (e.g., 4F); 3 bydroxybutyrldehyde to I,3-BDO (e.g., 4G); acetoacetyl-CoA to 3-hydroxybutyryl-CoA (e.g. 4H); 3-hydroxybutyryl-CoA to 3-hydroxybutyraldehyde (e.g., 41), 3-hydroxybutyryl-CoA to 1,3 BDO (e.g., 4J); acetoacetyl-CoA to acetoacetate (e.g., 4K); acetoacetate to 3-oxobutyraldehyde (e.g., 4L); 3-hydroxybutyrl-CoA to 3 -hydroxybutyrate (e.g., 4M); 3-hydroxybutyrate to 3 hydroxybutyraldehyde (e.g. 4IN); and acetoacetate to 3-hydroxybutyrate (e.g., 40). One skilled in the art will understand that these are merely exemplary and that any of the substrate-product pairs disclosed herein suitable to produce a desired product and for which an appropriate activity is available for the conversion of the substrate to the product can be readily determined by one skilled in the art based on the teachings herein. Thus, provided herein are non-naturally occurring eukaryotic organisms comprising at least one exogenous nucleic acid encoding an enzyme or protein, where the enzyme or protein converts the substrates and products of a 1.3 BDO pathway, such as that shown in FIGS. 4 or 7. [002311 Any combination and any number of the aforementioned enzymes and/or nucleic acids encoding the enzymes thereof, can be introduced into a host eukaryotic organism to complete a 1,3-BDO pathway, as exemplified in FIG. 4 or FIG. 7. For example, the non naturally occurring eukaryotic organism can include one, two, three, four, five, up to all of the nucleic acids in a 1,3-BDO pathway, each nucleic acid encoding a I,3-BDO pathway enzyme. Such nucleic acids can include heterologous nucleic acids, additional copies of existing genes, -113and gene regulatory elements, as explained further below. The pathways of the non-naturally occurring eukaryotic organisms provided herein are also suitably engineered to be cultured in a substantially anaerobic culture medium. [002321 in certain embodiments of the methods provided herein for increasing cytosolic acetyl CoA involves deleting or attenuating competing pathways that utilize acetyl-CoA. Deletion or attenuation of competing byproduct pathways that utilize acetyl-CoA can be carried out by any method known to those skilled in the art. For example, attenuation of such a competing pathway can be achieved by replacing an endogenous nucleic acid encoding an enzyme of the pathway for a mutated form of the nucleic acid that encodes for a variant of the enzyme with decreased enzymatic activity as compared to wild-type. Deletion of such a pathway can be achieved, for example, by deletion of one or more endogenous nucleic acids encoding for one or more enzymes of the pathway or by replacing the endogenous one or more nucleic acids with null allele variants. Exemplary methods for genetic manipulation of endogenous nucleic acids in host eukaryotic organisms, including Saccharonyces cerevisiae, are described below and in Example X. 1002331 For example, one such enzyme in a competing pathway that utilizes acetvl-CoA is the mitochondrial pyruvate dehydrogenase complex. Under anaerobic conditions and in conditions where glucose concentrations are high in the medium, the capacity of this mitochondrial enzyme is very limited and there is no significant flux through it. However, in some embodiments, any of the non-naturally occurring eukaryotic organisms described herein can be engineered to express an attenuated mitochondrial pyruvate dehydrogenase or a null phenotype to increase 1,3 BDO production. Exemplary pyruvate dehydrogenase genes include PDB1, PDAI, LATi and LPD . Exemplary competing acetyl-CoA consuming pathways whose attenuation or deletion can improve 1,3-BDO production include, but are not limited to, the mitochondrial TCA cycle and metabolic pathways, such as fatty acid biosynthesis and amino acid biosynthesis. 1002341 In certain embodiments, any of the eukaryotic organism provided herein is optionally further engineered to attenuate or delete one or more byproduct pathways, such as one or more of those exemplary byproduct pathways marked with an "X" in FIG. 7 or the conversion of 3 oxobutyraldehyde to acetoacetate by 3-oxobutyraldehyde dehydrogenase. For example, in one -114embodiment, the byproduct pathway comprises G3P phosphatase that converts G3P to glycerol. In another embodiment, the byproduct pathway comprises G3P dehydrogenase that converts dihydroxyacetone to G3P, and G3P phosphatase that converts G3P to glycerol. In other embodiments, the byproduct pathway comprises pyruvate decarboxylase that converts pyruvate to acetaldehyde. In another embodiment, the byproduct pathway comprises an ethanol dehydrogenase that converts acetaldehyde to ethanol. In other embodiments, the byproduct pathway comprises an acetaldehyde dehydrogenase (acylating) that converts acetyl-CoA to acetaldehyde and an ethanol dehydrogenase that converts acetaldehyde to ethanol. In other embodiments, the byproduct pathway comprises a pyruvate decarboxylase that converts pyruvate to acetaldehyde; and an ethanol dehydrogenase that converts acetaldehyde to ethanol. In other embodiments, the byproduct pathway comprises an acetaldehyde dehydrogenase (acylating) that converts acetyl-CoA to acetaldehyde and an ethanol dehydrogenase that converts acetaldehyde to ethanol. In certain embodiments, the byproduct pathway comprises an acetoacetyl-CoA hydrolase or transferase that converts acetoacetyl-CoA to acetoacetate. In another embodiment, the byproduct pathway comprises a 3-hydroxybutyri-CoA-hydrolase that converts 3 hydroxvbutvrvl-CoA (3--1BCoA) to 3-hydroxybutyrate. In another embodiment, the byproduct pathway comprises a 3-hydroxybutyraldehyde dehydrogenase that converts 3 hydroxybutyraldehyde to 3-hydroxybutyrate. In another embodiment, the byproduct pathway comprises a 1,3-butanediol dehydrogenase that converts 1,3-butanediol to 3-oxobutanol. In another embodiment, the byproduct pathway comprises a 3-oxobutyraldehyde dehydrogenase that converts 3-oxobutvraldehyde to acetoacetate. In another embodiment, the byproduct pathway comprises a mitochondrial pyruvate dehydrogenase. In another embodiment, the byproduct pathway comprises an acetoacetyl-CoA thiolase. 1002351 In an additional embodiment, provided herein is a non-naturally occurring eukaryotic organism having a 1 ,3-BDO pathway, wherein the non-naturally occurring eukaryotic organism comprises at least one exogenous nucleic acid encoding an enzyme or protein that converts a substrate to a product selected from the group consisting of 4B, 4C, 41D, 4E, 4F, 4G, 4H, 4I, 4J, 4L, 4N and 40. In sonie embodiments, the organism comprises a 1,3-BDO pathway comprising 4A, 4H, 41 and 4G. In other embodiments, the organism comprises a 1,3-BDO pathway -115comprising 7E, 7F. 4H, 4I and 4G. In some embodiments, the eukarvotic organism is further engineered to delete one or more of byproduct pathways as described herein. [00236] One skilled in the art will understand that these are merely exemplary and that any of the substrate-product pairs disclosed herein suitable to produce a desired product and for which an appropriate activity is available for the conversion of the substrate to the product can be readily determined by one skilled in the art based on the teachings herein. Thus, provided herein are non-naturally occurring eukaryotic organisms comprising at least one exogenous nucleic acid encoding an enzyme or protein, where the enzyme or protein converts the substrates and products of a 1,3-BDO pathway, such as those shown in FIG. 4 and FIG. 7. [002371 Any combination and any number of the aforementioned enzymes can be introduced into a host eukaryotic organism to complete a 1,3-3DO pathway, as exemplified in FIGS, 4 or 7. For example, the non-naturally occurring eukaryotic organism can include one, two, three, four, up to all of the nucleic acids in a I ,3-BDO pathway, each nucleic acid encoding a 1,3-BDO pathway enzyme. Such nucleic acids can include heterologous nucleic acids, additional copies of existing genes, and gene regulatory elements, as explained further below. The pathways of the non-naturally occurring eukaryotic organisms provided herein are also suitably engineered to be cultured in a substantially anaerobic culture medium. [002381 While, in certain embodiments, a eukaryotic organism is said to further comprise a 1,3-131)0 pathway, it is understood that also provided herein is a non-naturally occurring eukaryotic organism comprising at least one exogenous nucleic acid encoding a 1,3-BDO pathway enzyme expressed in a sufficient amount to produce an intermediate of a 1,3-BDO pathway. For example, as disclosed herein, a 1,3-BDO pathway is exemplified in FIGS. 4 or 7. Therefore, in addition to a eukaryotic organism containing a 1,3-BDO pathway that produces 1,3-13D0, provided herein is a non-naturally occurring eukaryotic organism comprising at least one exogenous nucleic acid encoding a 1 ,3-BDO pathway enzyme, where the eukarvotic organism produces a 1,3-3DO pathway intermediate, for example, acetoacetyl-CoA, acetoacetate, 3-oxobutyraldehyde, 3-hydroxybuturaldehyde, 4-hydroxy-2-butanone. 3 hydroxybutyrl-CoA, or 3-hydroxybutyrate. -116- [002391 It is understood that any of the pathways disclosed herein, as described in the Examples and exemplified in the figures, including the pathways of FIGS. 4 or 7, can be utilized to generate a non-naturally occurring eukaryotic organism that produces any pathway intermediate or product, as desired. As disclosed herein, such a eukaryotic organism that produces an intermediate can be used in combination with another eukaryotic organism expressing downstream pathway enzymes to produce a desired product. However, it is understood that a non-naturally occurring eukaryotic organism that produces a 1,3- B DO pathway intermediate can be utilized to produce the intermediate as a desired product. [002401 The conversion of acetyl-CoA to 1,3-BDO can be accomplished by a number of pathways involving about three to five enzymatic steps as shown in FIG. 4. In the first step of all pathways (Step A), acetyl-CoA is converted to acetoacetyl-CoA by enzyme 4A. Alternatively, acetyi-CoA is converted to malonyl-CoA by acetyl-CoA carboxylase (FIG. 7, step E), and acetoacetyl-CoA is synthesized from acetyl-CoA and malonyl-CoA by acetoacetyl-CoA synthase (FIG. 7, step F), [002411 In one route, 4A converts acetyl-CoA to acetoacetyl-CoA; 4E converts acetoacetyl CoA to 3-oxobutyraldehyde; 4F converts 3-oxobutyraldehyde to 3-hydroxybutyrldehyde, and 4(G converts 3-hydroxybutyrldehyde to 1,3-BDO. In another route, 4A converts acetyl-CoA to acetoacetyl-CoA; 413 converts acetoacetyl-CoA to 4-hydroxy-2-butanone; and 41) converts 4 hydroxy-2-butanone to 1,3-BDO. In one route, 4A converts acetyl-CoA to acetoacetyl-CoA; 4E converts acetoacetyl-CoA to 3-oxobutyraldehyde; 4C converts 3-oxobutyraldehyde to 4 hydroxy-2-butanone; and 4D converts 4-hydroxy-2-butanone to 1,3-BDO. In another route, 4A converts acetyl-CoA to acetoacetyl-CoA; 41- converts acetoacetyl-Co-A to 3-hydroxybutyryl CoA; and 4J converts 3-hydroxybutyryl-CoA to 1,3-BDO. In yet another route, 4A converts acetyl-CoA to acetoacetyl-CoA; 4H converts acetoacetyl-CoA to 3-hydroxybutyryl-CoA; 41 converts 3-hydroxybutyryl-CoA to 3-hydroxybutyraldehyde; and 4G converts 3 hydroxybutyrldehyde to 1,3-BDO. In another route, 4A converts acetyl-CoA to acetoacetyl CoA; 4[I converts acetoacetyl-CoA to 3-hydroxybutyryl-CoA; 4M converts 3-hydroxybutyrl CoA to 3-hydroxybutyrate; 4N converts 3 -hydroxybutyrate to 3-hydroxybutyraldehyde; and 4G converts 3-hydroxybutyrldehyde to 1,3-BDO. In one route, 4A converts acetyl-CoA to -117acetoacetyl-CoA; 4K converts acetoacetyl-CoA to acetoacetate; 40 converts acetoacetate to 3 hydroxybutyrate; 4N converts 3-h droxybutyrate to 3-hydroxybutyraldehyde; and 4G converts 3-hydroxybutyrIdehyde to 1 ,3-BDO. In another route, 4A converts acetyl-CoA to acetoacetyl CoA; 4K converts acetoacetyl-CoA to acetoacetate; 4L converts acetoacetate to 3 oxobutyraldehyde; 4F converts 3-oxobutyraldehyde to 3-hydroxybutyrldehyde; and 4G converts 3-hydroxybutyridehyde to 1,3-BDO. [002421 Based on the routes described above for the production of 1,3-BDO from acetyl-CoA, in some embodiments, the non-naturally occurring eukaryotic organism has a set of 1,3-13DO pathway enzymes that includes 4A, 4E, 4F and 4G; 4A, 4B and 4D; 4A, 4E, 4C and 4D; 4A, 4H and 4J; 4A, 41], 41 and 4G; 4A, 4H, 4M, 4N and 4G; 4A, 4K, 40, 4N and 4G; or 4A, 4K, 4L, 4F and 4G. Any number of nucleic acids encoding these enzymes can be introduced into the host organism including one, two, three, four or up to all five of the nucleic acids that encode these enzymes. Where one, two, three or four exogenous nucleic acids are introduced, for example, such nucleic acids can be any permutation of the five nucleic acids. The sane holds true for any other number of exogenous nucleic acids that is less than the number of enzymes being encoded. 1002431 In another route, 7E converts acetyl-CoA to malonyl-CoA and 7F converts malonyl CoA and acetyl-CoA to acetoacetyl-CoA; 4E converts acetoacetyl-CoA to 3-oxobutyTaldehyde; 4F converts 3-oxobutyraldehyde to 3-hydroxybutyridehyde, and 4G converts 3 hydroxybutyrldehyde to 1,3-BDO. In another route, 7E converts acetyl-CoA to malonyl-CoA and 7F converts malonyl-CoA and acetyl-CoA to acetoacetyl-CoA; 4B converts acetoacetyl-CoA to 4-hydroxy-2-butanone; and 4D converts 4-hydroxy-2-butanone to 1,3-BDO. In one route, 7E converts acetyl-CoA to mnalonyl-CoA and 7F converts malonyl-CoA and acetyl-CoA to acetoacetyl-CoA; 4E converts acetoacetyl-CoA to 3-oxobutyraldehyde; 4C converts 3 oxobutyraldehyde to 4-hydroxy-2-butanone; and 4D converts 4-hydroxy-2-butanone to 1,3 BDO. In another route, 7E converts acetyl-CoA to malonyl-CoA and 7F converts malonyl-CoA and acetyl-CoA to acetoacetyl-CoA; 4H converts acetoacetyl-CoA to 3-hydroxybutyryi-CoA; and 4J converts 3-hydroxybutyryl-CoA to 1,3-13D). In yet another route, 7E converts acetvl CoA to malonyl-CoA and 7F converts malonyl-CoA and acetyl-CoA to acetoacetyl-CoA; 4H converts acetoacetyl-CoA to 3-hydroxybutyryl-CoA; 41 converts 3-hydroxybutyryl-CoA to 3 -118hydroxybutyraldehyde; and 4G converts 3-hydroxybutyridehyde to 1,3-BDO. In another route, 7E converts acetyl-CoA to malonyl-CoA and 7F converts malonyl-CoA and acetyl-CoA to acetoacetyl-CoA; 4H converts acetoacetyl-CoA to 3-hydroxybutyryi-CoA; 4M converts 3 hydroxybutyrl-CoA to 3-hydroxybutyrate; 4N converts 3-hydroxybutyrate to 3 hydroxybutyraldehyde; and 4G converts 3-hydroxybutyrldehyde to 1 ,3-BDO. In one route, 7E converts acetyl-CoA to malonyl-CoA and 7F converts malonyl-CoA and acetyl-CoA to acetoacetyl-CoA; 4K converts acetoacetyl-CoA to acetoacetate; 40 converts acetoacetate to 3 hydroxybutyrate;- 4N converts 3-hydroxybutyrate to 3-hydroxybutyraldehyde; and 4G converts 3-hvdroxybutyrldehyde to 1,3-BDO. In another route, 7E converts acetyl-CoA to malonyl-CoA and 7F converts malonyl-CoA and acetyl-CoA to acetoacetyl-CoA;- 4K converts acetoacetyl CoA to acetoacetate; 4L converts acetoacetate to 3-oxobutyraldehyde; 41 converts 3 oxobutyraIdehyde to 3-hydroxybutyrldehyde; and 4G converts 3-hydroxybutyridehyde to 1,3 BDO. [002441 Based on the routes described above for the production of I,3-BDO from acetyl-CoA, in some embodiments, the non-naturally occurring eukaryotic organism has a set of 1,3-BDO pathway enzymes that includes 7E, 7F, 4E, 4F and 4G; 7E, 7F, 4B and ID; 7E. 7F, 4E, 4C and 4D; 7E, 7F, 4H and 43; 7E, 7F, 4-, 41 and 4G; 7E, 7, 41-1, 4M, 4N and 4G 7E, 7, 4K, 40, 4N and 4G; or 7E, 7F, 4K, 41. 4F and 4G. Any number of nucleic acids encoding these enzymes can be introduced into the host organism including one, two, three, four or up to all five of the nucleic acids that encode these enzymes. Where one, two, three or four exogenous nucleic acids are introduced, for example, such nucleic acids can be any permutation of the five nucleic acids. The same holds true for any other number of exogenous nucleic acids that is less than the number of enzymes being encoded. [002451 The organism can optionally be further engineered to delete one or more of the exemplary byproduct pathways ("X") as described elsewhere herein. Based on these routes for the production of 1,3-BDO from acetyl-CoA, in some embodiments, the non-naturally occurring eukaryotic organism has a set of 1,3-BDO pathway enzymes that includes 4A, 41-, 41 and 4G; or 7E, 7F, 4H, 41 and 4G. Any number of nucleic acids encoding these enzymes can be introduced into the host organism including one, two, three, four or up to all five of the nucleic acids that -119encode these enzymes. Where one, two, or three exogenous nucleic acids are introduced, for example, such nucleic acids can be any permutation of the four or five nucleic acids. The same holds true for any other number of exogenous nucleic acids that is less than the number of enzymes being encoded. 4.3 Combined Cytosolic//Mitochondrial 1,3-BDO Pathways [00246] A eukaryotic organism, as provided herein, can also be engineered to efficiently direct carbon and reducing equivalents into a combined mitochondrial/cytosolic I,3-BDO pathway. Such a pathway would require synthesis of a monocarboxylic I ,3-BDO pathway intennediate such as acetoacetate or 3-hydroxybutyrate in the mitochondria, export of the pathway intermediate to the cytosol, and subsequent conversion of that intermediate to 1,3-BDO in the cytosol. Exemplary combined mitochondrial/cytosolic 1,3-3DO pathways are depicted in Figure 8. [002471 There are several advantages to producing 1,3-BDO using a combined mitochondrial/cytosolic 1,3-3DO production pathway. One advantage is the naturally abundant mitochondrial pool of acetyl-CoA, the key I,3-BDO pathway precursor. Having a I ,3-BDO pathway span multiple compartments can also be advantageous if pathway enzymes are not adequately selective for their substrates. For example, 3-hydroxybutyryl-CoA reductase and 3 hydroxybutyryaldehyde enzym es may also reduce acetyl-CoA to ethanol. Sequestration of the acetvl-CoA pool in the mitochondria could therefore reduce formation of by products derived from acetyl-CoA. A combined mitochondrial/cytosolic 1,3-BDO pathway could benefit from attenuation of mitochondrial acetyl-CoA consuming enzymes or pathways such as the TCA cycle. [002481 Acetoacetate and 3-hydroxybutyrate are readily transported out of the mitochondria by pyruvate and/or monocarboxylate transporters. The existence of a proton syniporter for the uptake of pyruvate and also for acetoacetate was demonstrated in isolated mitochondria (Briquet. Biochein Biophys Acta 459:290-99 (1977)). However, the gene encoding this transporter has not been identified to date. S. cerevisiae encodes five putative monocarboxylate transporters (MCH1-5), several of which may be localized to the mitochondrial membrane (Makuc et al, -120- Yeast 18:1131-43 (2001)). NDTI is another putative pyruvate transporter, although the role of this protein is disputed in the literature (Todisco et al, J Biol Chem 20:1524-31 (2006)), Exemplary monocarboxylate transporters are shown in the table below: TABLE 1 Protein GenBank ID GI number Organism M11CH1 N1P 010229.1 6320149 Saccharomvces cerevisiae CH__2 _NP_0127.2 330443640___ Sacharomgces cerezsiae H3_NP 014274.1 6324204_ Sacharoaoves cerevisa MCH5 NP 014951.2 330443742 Saccharomvces cerevisiae NDTI NP 012260.1 6322185 Saccharomves cerevisiae ANI 1 1592184 XP 001401484 2 317038471 Aspergilius niger CaJ7 0216 XP 888808,1 77022728 Candida albicans YALIOE164 78g XP_504023.1 50553226 Yarrowia lipolytica KL L AD4036g XP_453688.1 50307419 Khnyveromyces lactis [002491 In certain embodiments, the combined mitochondrial/cytosolic 1,3-BDO pathway comprises 8A, 8B, 8C, 8D, 8E. 8F, 8G, 8H, 8I, 8J, 8K. 7E, 7F, 4A, 4B. 4C, 4D, 4E, 4F. 4-G, 4H, 41, 4J, 4K, 4L, 4M, 4N, and 40, or any combination of 8A, 8B, 8C, 8D, 8E, 8F, 8G, 811, 81, 8, 8K, 7E, 7F, 4A, 4B, 4C, 4D, 4E, 4F, 4G, 4H, 41I, 4, 4K, 4L, 4M, 4N, and 40 thereof, wherein 8A is a mitochondrial acetoacetyl-CoA thiolase; 8B is a mitochondrial acetoacetyl-CoA reductase; 8C is a mitochondrial acetoacetvl-CoA hydrolase, transferase or synthetase; 8D is a mitochondrial 3-hydroxybutyryl-CoA hydrolase, transferase or synthetase; 8E is a mitochondrial. 3-hydroxybutyrate dehydrogenase; 8F is an acetoacetate transporter; 8G is a 3 hydroxybutyrate transporter; 8H is a 3-hydroxybutyryl-CoA transferase or synthetase, 8I is a cytosolic acetoacetyl-CoA transferase or synthetase, 8.1 is a mitochondrial acetyl-CoA carboxylase; 8K is a mitochondrial acetoacetyl-CoA synthase; 7E is acetyl-CoA carboxylase, 7F is acetoacetyl-CoA synthase, 4A is an acetoacetyl-CoA thiolase; 4B is an acetoacetyl-CoA reductase (CoA-dependent, alcohol foning); 4C is a 3-oxobutyraldehyde reductase (aldehyde reducing); 4D is a 4-hydroxy,2-butanone reductase; 4E is an acetoacetyl-CoA reductase (CoA dependent, aldehyde forming); 4F is a 3-oxobutyraldehyde reductase (ketone reducing); 4G is a 3-hydroxybutyraldehyde reductase; 4H is an acetoacetyl-CoA reductase (ketone reducing); 41 is a 3-hydroxybutyryl-CoA reductase (aldehyde forming); 4.! is a 3-hydroxybutyryl-CoA reductase -121- (alcohol forming); 4K is an acetoacetyl-CoA transferase, an acetoacetyl-CoA hydrolase, an acetoacetyl-CoA synthetase, or a phosphotransacetoacetylase and acetoacetate kinase; 4L is an acetoacetate reductase; 4M is a 3-hydroxybutyryl-CoA transferase, hydrolase, or synthetase; 4N is a 3-hydroxybutyrate reductase; and wherein 40 is a 3-hydroxybutyrate dehydrogenase. In certain embodiments, 8C is a mitochondrial acetoacetyl-CoA hydrolase. In other embodiments, 8C is a mitochondrial acetoacetyl-CoA transferase. In certain embodiments, 8C is a mitochondrial acetoacetyl-CoA synthetase. In certain embodiments 8D is a mitochondrial 3 hydroxybutyryl-CoA hydrolase. In other embodiments 8D is a mitochondrial 3-hydroxybutyryl CoA transferase. In certain embodiments 8D is a mitochondrial 3-hydroxybutyryi-CoA synthetase. In certain embodiments, 8H is a 3-hydroxybutyryl-CoA transferase. In other embodiments, 81- is a 3-hydroxybutyryl-CoA synthetase. In certain embodiments, 8I is a cytosolic acetoacetyl-CoA transferase. In other embodiments, 8I is a cytosolic acetoacetyl-CoA synthetase. In certain enbodiments, 4K is an acetoacetyl-CoA transferase. In other embodiments, 4K is an acetoacetyl-CoA hydrolase. In some embodiments, 4K is an acetoacetyl CoA synthetase. In other embodiments, 4K is a phosphotransacetoacetylase and acetoacetate kinase. In certain embodiments, 4M is a 3-hydroxybutyryl-CoA transferase. In some embodiments., 4M is a 3-hydroxybutyryl-CoA, hydrolase. In yet other embodiments, 4M is a 3 hydroxybutyryl-CoA synthetase. 1002501 In another aspect, provided herein is a non-naturally occurring eukaryotic organism comprising: (1) an acetoacetate pathway, wherein said organism comprises at least one exogenous nucleic acid encoding an acetoacetate pathway enzyme expressed in a sufficient amount to increase acetoacetate in the cytosol of said organism, wherein said acetoacetate pathway comprises 8A, 8C, and 8F, wherein 8A is a mitochondrial acetoacetyl-CoA thiolase; 8C is a mitochondrial acetoacetyl-CoA hydrolase, transferase or synthetase; and 8F is an acetoacetate transporter; and (2) a i.3-BDO pathway, wherein said organism comprises at least one exogenous nucleic acid encoding a 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO in the cytosol of said organism, and wherein the 1,3-BDO pathway comprises a pathway selected from: (i) 40, 4N, and 4G; and (ii) 4L, 4F, and 4G; wherein 4F is a 3-oxobutyraldehyde reductase (ketone reducing); 4G is a 3-hydroxybutyraldehyde reductase; 4L is an acetoacetate reductase; 4N is a 3-hydroxybutyrate reductase; and 40 is a 3-hydroxybutyrate -122dehydrogenase. In some embodiments, the 1,3-BDO pathway comprises 40, 4N and 4G. In other embodiments, the 1,3-3DO pathway comprises 4L, 4F, and 4G. [002511 In another aspect, provided herein is a non-naturally occurring eukaryotic organism comprising: (1) an acetoacetate pathway, wherein said organism comprises at least one exogenous nucleic acid encoding an acetoacetate pathway enzyme expressed in a sufficient amount to increase acetoacetate in the cytosol of said organism, wherein said acetoacetate pathway comprises 8J, 8K, 8C, and 8F, wherein 8J is a mitochondrial acetyl-CoA carboxylase; 8K is a mitochondrial acetoacetyl-CoA synthase; SC is a mitochondrial acetoacetyl-CoA hvdrolase, transferase or synthetase; and SF is an acetoacetate transporter; and (2) a 1,3-BDO pathway, wherein said organism comprises at least one exogenous nucleic acid encoding a 1,3 BDO pathway enzyme expressed in a sufficient amount to produce I,3-BDO in the cytosol of said organism, and wherein the 1,3-BDO pathway comprises a pathway selected from: (i) 40, 4N, and 4G; and (ii) 4L, 4F, and 4G; wherein 4F is a 3-oxobutyraldehyde reductase (ketone reducing); 4G is a 3-hydroxybutyraldehyde reductase; 4L is an acetoacetate reductase; 4N is a 3 hydroxybutyrate reductase; and 40 is a 3-hydroxybutyrate dehydrogenase. In some embodiments, the 1,3-BDO pathway comprises '10, 4N and 4G. In other embodiments, the 1,3 BDO pathway comprises 4L, 4F, and 4G. [002521 In another aspect, provided herein is a non-naturally occurring eukaryotic organism comprising: (1) an acetoacetyl-CoA pathway, wherein said organism comprises at least one exogenous nucleic acid encoding an acetoacetyl-CoA pathway enzyme expressed in a sufficient amount to increase acetoacetyl-CoA in the cytosol of said organism, wherein said acetoacetyl CoA pathway comprises 8A, 8C, 8F and 81, wherein 8A is a mitochondrial acetoacetyl-CoA thiolase; 8C is a mitochondrial acetoacetyl-CoA hydrolase, transferase or synthetase; 8F is an acetoacetate transporter and 81 is a cytosolic acetoacetyl-CoA transferase or synthetase; and (2)a 1,3-13DO pathway, wherein said organism comprises at least one exogenous nucleic acid encoding a I ,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO in the cytosol of said organism, and wherein the 1,3-13D0 pathway comprises a pathway selected from: (i) 4E, 4F and 4G; (ii) 4B and 4D; (iii) 4E, 4C and 4D; (iv) 4H and 4J; (v) 4H,1 41 and 4G; and (vi) 4H, 4M, 4N and 4G; wherein 4B is an acetoacetyl-CoA reductase (CoA-dependent, -123alcohol forming); 4C is a 3-oxobutyraldehyde reductase (aldehyde reducing); 4D is a 4 hydroxy,2-butanone reductase; 4E is an acetoacetyl-CoA reductase (CoA-dependent, aldehyde fonning); 4F is a 3-oxobutyraldehyde reductase (ketone reducing); 4G is a 3 hydroxybutyraldehyde reductase; 4H is an acetoacetyl-CoA reductase (ketone reducing); 41 is a 3-hydroxybutyryl--CoA reductase (aldehyde forming); 4J is a 3-hydroxybutyryl-CoA reductase (alcohol forming); 4L is an acetoacetate reductase; 4M is a 3-hydroxybutyryl-CoA transferase, hydrolase, or synthetase; and 4N is a 3-hydroxybutyrate reductase. In some embodiments, the 1,3-BDO pathway comprises 4E, 4F and 4G. In some embodiments, the 1,3-BDO pathway comprises 4B and 41). In other embodiments, 1,3-BDO pathway comprises 41, 4C and 41). In another embodiment, 1,3-BDO pathway comprises 4H and 4J. In another embodiment, the 1,3 BDO pathway comprises 4H, 41 and 4G. In other embodiments, the 1,3-3DO pathway comprises 4H, 4M, 4N and 4G. [002531 In another aspect, provided herein is a non-naturally occurring eukaryotic organism comprising: (1) an acetoacetyl-CoA pathway, wherein said organism comprises at least one exogenous nucleic acid encoding an acetoacetyl-CoA pathway enzyme expressed in a sufficient amount to increase acetoacetyl-CoA in the cytosol of said organism., wherein said acetoacetyl CoA pathway comprises 8J, 8K, 8C, 8F and 81, wherein 8. is a mitochondrial acetyl-CoA carboxylase; 8K is a mitochondrial acetoacetyl-CoA synthase; 8C is a mitochondrial acetoacetyl CoA hydrolase, transferase or synthetase; 8F is an acetoacetate transporter; and 8I is a cytosolic acetoacetyl-CoA transferase or synthetase; and (2)a I ,3-BDO pathway, wherein said organism comprises at least one exogenous nucleic acid encoding a 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO in the cytosol of said organism, and wherein the 1,3 BDO pathway comprises a pathway selected from: (i) 4E, 4F and 4G; (ii) 4B and 4D; (iii) 4E, 4C and 41); (iv) 41 and 4J; (v) 4[I, 41 and 4G; and (vi) 4H, 41, 4N and 4G; wherein 4B is an acetoacetyl-CoA reductase (CoA-dependent, alcohol forming); 4C is a 3-oxobutyraldehyde reductase (aldehyde reducing); 4D is a 4-hydroxy,2-butanone reductase; 4E is an acetoacetyl CoA reductase (CoA-dependent, aldehyde forming); 4F is a 3-oxobutyraldehyde reductase (ketone reducing); 4G is a 3-hydroxybutyraldehyde reductase; 4H is an acetoacetyl-CoA reductase (ketone reducing); 41 is a 3-hydroxybutyryl-CoA reductase (aldehyde forcing); 4J is a 3-hydroxybutyryl-CoA reductase (alcohol forming); 4L is an acetoacetate reductase; 4M is a 3 -124hydroxybutyryl-CoA transferase, hydrolase, or synthetase; and 4N is a 3-hydroxybutyrate reductase. In some embodiments, the I,3-BDO pathway comprises 4E, 4F and 4G. In some embodiments, the 1,3-BDO pathway comprises 4B and 4D. in other embodiments, 1,3-BDO pathway comprises 4E, 4C and 4D. In another embodiment, 1,3-BDO pathway comprises 4H and 4J. In another embodiment, the 1,3-BDO pathway comprises 4H, 41 and 4G. In other embodiments, the 1,3-BDO pathway comprises 41, 4M, 4N and 4G. [002541 In another aspect, provided herein is a non-naturally occurring eukaryotic organism comprising: (1) a 3-hydroxybutyrate pathway, wherein said organism comprises at least one exogenous nucleic acid encoding a 3-hydroxybutyrate pathway enzyme expressed in a sufficient amount to increase 3-hydroxybutyrate in the cytosol of said organism, wherein said 3 hydroxybutyrate pathway comprises a pathway selected from: (i) 8A, 8B. 8D and 8G; and (ii) 8A, 8C, 8E arid SG; wherein 8A is a mitochondrial acetoacetyl-CoA thiolase; 8B is a mitochondrial acetoacetyl-CoA reductase; 8C is a mitochondrial acetoacetyl-CoA hydrolase, transferase or synthetase; 8D is a mitochondrial 3-hydroxybutyryl-CoA hydrolase, transferase or synthetase; 8E is a mitochondrial 3-hydroxybutyrate dehydrogenase; and 8G is a 3 hydroxybutyrate transporter; and (2) a 1,3-BDO pathway, wherein said organism comprises at least one exogenous nucleic acid encoding a 1,3-13DO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO in the cytosol of said organism, and wherein the 1,3-BDO pathway comprises 4N and 4G, wherein 4G is a 3-hydroxybutyraldehyde reductase; and 4N is a 3 hydroxybutyrate reductase. In one embodiment, the 3 -hydroxybutyrate pathway comprises 8A, 8B, 8D and 8G. In another embodiment, the 3-hydroxybutyrate pathway comprises 8A, 8C, 8E and 8G. [002551 In another aspect, provided herein is a non-naturally occurring eukaryotic organism comprising: (1) a 3-hydroxybutyrate pathway, wherein said organism comprises at least one exogenous nucleic acid encoding a 3-hydroxybutyrate pathway enzyme expressed in a sufficient amount to increase 3-hydroxybutyrate in the cytosol of said organism, wherein said 3 hydroxybutyrate pathway comprises a pathway selected from: (i) 8J, 8K, 8E, 8D and 8G; and (ii) 8J, 8K, 8C, 8E and 8G; wherein 8J is a mitochondrial acetyl-CoA carboxylase; 8K is a mitochondrial acetoacetyl-CoA synthase; 8B is a mitochondrial acetoacetvl-CoA reductase; 8C -125is a mitochondrial acetoacetyl-CoA hydrolase, transferase or synthetase; 8D is a mitochondrial 3 hydroxybutvryl-CoA hydrolase, transferase or synthetase; 8E is a mitochondrial 3 hydroxybutyrate dehydrogenase; and 8G is a 3-hydroxybutyrate transporter; and (2) a 1,3-BDO pathway, wherein said organism comprises at least one exogenous nucleic acid encoding a 1,3 BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO in the cytosol of said organism, and wherein the 1,3-BDO pathway comprises 4N and 4G, wherein 4G is a 3 hydroxybutvraidehyde reductase; and 4N is a 3-hydroxybutyrate reductase. In one embodiment, the 3-hydroxybutyrate pathway comprises 8J, 8K, 8B, 8D and 8G. In another embodiment, the 3-hvdroxybutyrate pathway comprises SJ, 8K, 8C, 8E1 and 8G. 1002561 In another aspect, provided herein is a non-naturally occurring eukaryotic organism comprising: (1) a 3-hydroxybutyryl-CoA pathway, wherein said organism comprises at least one exogenous nucleic acid encoding a 3-hydroxybutNyl-CoA pathway enzyme expressed in a sufficient amount to increase 3-hydroxybutyryl-CoA in the cytosol of said organism, wherein said 3-hydroxybutyryl-CoA pathway comprises a pathway selected from: (i) 8A, 8B, 8D, 8G and 8H; and (ii) 8A, 8C, 8E, 8G and 8H; wherein 8A is a mitochondrial acetoacetyl-CoA thiolase; 8B is a mitochondrial acetoacetyl-CoA reductase; 8C is a mitochondrial acetoacetyl-CoA hydrolase, transferase or synthetase; 8D is a mitochondrial 3-hydroxybutyryl-CoA hydrolase, transferase or synthetase; 8E is a mitochondrial 3-hydroxybutyrate dehydrogenase; 8G is a 3 hydroxybutyrate transporter; and 8-I is a 3-hyd roxy bu tyryl-CoA transferase or synthetase, and (2) a 1,3-BDO pathway, wherein said organism comprises at least one exogenous nucleic acid encoding a I ,3-BDO pathway enzyme expressed in a sufficient amount to produce 1 ,3-BDO in the cytosol of said organism, and wherein the l,3-BDO pathway comprises a pathway selected from: (i) 41 and 4G; and (i) 4J; wherein 41 is a 3-hydroxybutryl-CoA reductase (aldehyde forming); wherein 4G is a 3-hydroxybutyraldehyde reductase; and 4.1 is a 3-hydroxybutyryl-CoA reductase (alcohol forming). In certain embodiments, the 3-hydroxybutyryl-CoA pathway comprises 8A, 8B, 8D, 8G, and 81, and the 1,3-BDO pathway comprises 41 and 4G. In other embodiments, the 3-hydroxybutyryl-CoA pathway comprises 8A, 8B, 8D, 8G. and 8H, and the 1,3-BDO pathway comprises 4J. In another embodiment, the 3-hydroxybIutyryl-CoA pathway comprises 8A, 8C, 8E, 8G, and 8H, and the 1,3-BDO pathway comprises 41 and 4G. In yet -126another embodiment, the 3-hydroxybutyryl-CoA pathway comprises 8A, 8C, 8E. 8G, and 8H, and the I,3-BDO pathway comprises 4J. [00257] In another aspect, provided herein is a non-naturally occurring eukarvotic organism comprising: (1) a 3-hydroxybutyryl-CoA pathway, wherein said organism comprises at least one exogenous nucleic acid encoding a 3-hydroxybutyryl-CoA pathway enzyme expressed in a sufficient amount to increase 3-hydroxybutyryl-CoA in the cytosol of said organism, wherein said 3-hydroxybutyryl-CoA pathway comprises a pathway selected from: (i) 8J. 8K, 8B. 8D, 8G and 81-I; and (ii) 8J, 8K, 8C, 8IE, 8G and 81; wherein 8. is a mitochondrial acetyl-CoA carboxylase; 8K is a mitochondrial acetoacetyl-CoA synthase; 8B is a mitochondrial acetoacetyl-CoA reductase; 8C is a mitochondrial acetoacetyl-CoA hydrolase, transferase or synthetase; 8D is a mitochondrial 3-hydroxybutyryl-CoA hydrolase, transferase or synthetase; 8E is a mitochondrial 3-hydroxybutyrate dehydrogenase; 8 is a 3-hydroxybutyrate transporter; and 8H is a 3-hydroxybutyryl-CoA transferase or synthetase, and (2) a I,3-BDO pathway, wherein said organism comprises at least one exogenous nucleic acid encoding a 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO in the cytosol of said organism, and wherein the 1,3-BDO pathway comprises a pathway selected from: (i) 41 and 4G and (ii) 4.; wherein 41 is a 3-hydroxybutyryl-CoA reductase (aldehyde forming); wherein 4G is a 3-hydroxybutyraldehyde reductase; and 4J is a 3-hydroxybutyryl-CoA reductase (alcohol forming). In certain embodiments, the 3-hydroxybutyryl-CoA pathway comprises 8A, 8B, 8D, 8G, and 8H, and the 1,3-BDO pathway comprises 41 and 4G. In other embodiments, the 3 hydroxybutyryl-CoA pathway comprises 8A, 8B, 8D, 8G, and 81, and the 1,3-BDO pathway comprises 4J. In another embodiment, the 3-hydroxybutyryl-CoA pathway comprises 8J, 8K, 8C, 8E, 8G, and 81, and the I,3-BDO pathway comprises 41 and 4G, In yet another embodiment, the 3-hydroxybutyryl-CoA pathway comprises 8J, 8K, 8C, 8IE, 8G, and 8H, and the 1,3-BDO pathway comprises 4J. [002581 One skilled in the art will understand that these are merely exemplary and that any of the substrate-product pairs disclosed herein suitable to produce a desired product and for which an appropriate activity is available for the conversion of the substrate to the product can be readily determined by one skilled in the art based on the teachings herein. Thus, provided herein -127are non-naturally occurring eukaryotic organisms comprising at least one exogenous nucleic acid encoding an enzyme or protein, where the enzyme or protein converts the substrates and products of a combined mitochondrial/cytosolic 1,3-BDO pathway, such as those shown in FIG. 8. [002591 Any combination and any number of the aforementioned enzymes can be introduced into a host eukaryotic organism to complete a combined mitochondrial/cytosolic I ,3-BDO pathway, as exemplified in FIG. 8. For example, the non-naturally occurring eukaryotic organism can include one, two, three, four, five, six, seven, up to all of the nucleic acids in a combined mitochondrial/cytosolic 1,3-BDO pathway, each nucleic acid encoding a combined mitochondrial/cytosolic 1,3-BDO pathway enzyme. Such nucleic acids can include heterologous nucleic acids, additional copies of existing genes, and gene regulatory elements, as explained further below. The pathways of the non-naturally occurring eukaryotic organisms provided herein are also suitably engineered to be cultured in a substantially anaerobic culture medium. 4.4 Balancing Co-factor Usage 1002601 1,3-BDO production pathways, such as those depicted in FIG. 4, require reduced cofactors such as NAD(P)H. Therefore, increased production of 1,3-BDO can be achieved, in part, by engineering any of the non-naturally occurring eukaryotic organisms described herein to comprise pathways that supply NAD(P)H cofactors used in 1,3-BDO production pathways. In several organisms, including eukaryotic organisms, such as several Saccharomyces, Kluvveronyces, Candida, Aspergillus, and Yarrowia species, NADH is more abundant than NADPH in the cytosol as NADH is produced in large quantities by glycolysis. Levels of NADII can be increased in these eukaryotic organisms by converting pyruvate to acetyl-CoA through any of the following enzymes or enzyme sets: 1) an NAD-dependent pyruvate dehydrogenase; 2) a pyruvate format lyase and an NAD-dependent formate dehydrogenase; 3) a pyruvate:ferredoxin oxidoreductase and an NADI-:ferredoxin oxidoreductase; 4) a pyruvate decarboxylase and an NAD-dependent acylating acetylaldehyde dehydrogenase; 5) a pyruvate decarboxylase. a NAD-dependent acylating acetaldehyde dehydrogenase, an acetate kinase, and a phosphotransacetylase; and 6) a pyruvate decarboxylase, an NAD-dependent acylating acetaldehyde dehydrogenase, and an acetyl-CoA synthetase. -128- [002611 As shown in FIG. 4. the conversion of acetyl-CoA to 1,3-BDO can occur, in part, through three reduction steps. Each of these three reduction steps utilize either NADPH or NADH as the reducing agents, which, in turn, is converted into molecules of NADP or NAD, respectively. Given the abundance of NADII in the cytosol of some organisms, it can be beneficial in some embodiments for all reduction steps of the 1,3-BDO pathway to accept NADH as the reducing agent. High yields of 1,3-BDO can therefore be accomplished by: 1) identifying and implementing endogenous or exogenous 1,3-13DO pathway enzymes with a stronger preference for NADH than other reducing equivalents such as NADPH; 2) attenuating one or more endogenous 1,3-B3D0 pathway enzymes that contribute NA DPI--dependent reduction activity; 3) altering the cofactor specificity of endogenous or exogenous 1,3-BDO pathway enzymes so that they have a stronger preference for NADII than their natural versions, and/or 4) altering the cofactor specificity of endogenous or exogenous 1,3-BDO pathway enzymes so that they have a weaker preference for NA DPH than their natural versions. [002621 In another aspect, provided herein is a method for selecting an exogenous I1,3-BDO pathway enzyme to be introduced into a non-naturally occurring eukaryotic organism, wherein the exogenous 1,3-BDO pathway enzyme is expressed in a sufficient amount in the organism to produce I,3-BDO, said method comprising (i) measuring the activity of at least one 1,3-3DO pathway enzyme that uses NADH as a cofactor; (ii) measuring the activity of at least 1.3-BDO pathway enzyme that uses NADPH as a cofactor; and (iii) introducing into the organism at least one 1,3-BDO pathway enzyme that has a greater preference for NADH than NADPH as a cofactor as determined in steps (i) and (ii). [00263] In another aspect, provided herein is a non-naturally eukarvotic organism comprising a 1,3-BDO pathway, wherein said organism further comprises: (1) a 1,3-BDO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a 1,3 BDO pathway enzyme expressed in a sufficient amount to produce 1,3-3DO; and (2) an acetyl CoA pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding an acetyl-CoA pathway enzyme expressed in a sufficient amount to increase NADH in the organism; wherein the acetyl-CoA pathway comprises (i) an NAD dependent pyruvate dehydrogenase; (ii.) a pyruvate fornate lyase and an N AD-dependent -129formate dehydrogenase; (iii.) a pyruvate:ferredoxin oxidoreductase and an NADH:ferredoxin oxidoreductase; (iv.) a pyruvate decarboxylase and an NAD-dependent acylating acetylaldehyde dehydrogenase; (v.) a pyruvate decarboxylase, a NAD-dependent acylating acetaldehyde dehydrogenase, an acetate kinase, and a phosphotransacetylase; or (vi.) a pyruvate decarboxylase, an NAD-dependent acylating acetaldehyde dehydrogenase, and an acetyl-CoA synthetase. In some embodiments, the acetyl-CoA pathway comprises an N-AD-dependent pyruvate dehydrogenase. In other embodiments, the acetyl-CoA pathway comprises an a pyruvate formate lyase and an NAD-dependent formate dehydrogenase. In other embodiments, the acetvl-CoA pathway comprises a pyruvate:ferredoxin oxidoreductase and an NADH:ferredoxin oxidoreductase. In other embodiments, the acetyl-CoA pathway comprises a pyruvate decarboxylase and an NAD-dependent acylating acetylaldehyde dehydrogenase. In other embodiments, the acetyl-CoA pathway comprises a pyruvate decarboxylase, a NAD dependent acylating acetaldehyde dehydrogenase, an acetate kinase, and a phosphotransacetylase. In yet other embodiments, the acetyl-CoA pathway comprises a pyruvate decarboxylase, an NAD-dependent acylating acetaldehyde dehydrogenase, and an acetyl-CoA synthetase. [002641 In another aspect, provided herein is a non-naturally eukarvotic organism comprising a 1,3-BDO pathway, wherein said organism further comprises one or more endogenous and/or exogenous nucleic acids encoding a 1,3-BD0 pathway enzyme selected from the group consisting of 4B, 4C, 4D, 4E, 4F, 4G, 4H, 41, 4J, 4L, 4N, and 40; wherein at least one nucleic acid has been altered such that the 1,3-BDO pathway enzyme encoded by the nucleic acid has a greater affinity for NADH than the 1,3-BDO pathway enzyme encoded by an unaltered or wild type nucleic acid. In some embodiments, the eukarvotic organism comprises a nucleic acid encoding 4B. In some embodiments, the eukaryotic organism comprises a nucleic acid encoding 4C. In some embodiments, the eukaryotic organism comprises a nucleic acid encoding 4D. In some embodiments, the eukaryotic organism comprises a nucleic acid encoding 4E. In some embodiments, the eukaryotic organism comprises a nucleic acid encoding 4F. in some embodiments, the eukaryotic organism comprises a nucleic acid encoding 4G. In some embodiments, the eukaryotic organism comprises a nucleic acid encoding 4H. In some embodiments, the eukaryotic organism comprises a nucleic acid encoding 41. In some -130embodiments, the eukaryotic organism comprises a nucleic acid encoding 4J. In some embodiments, the eukaryotic organism comprises a nucleic acid encoding 4L. In some embodiments, the eukaryotic organism comprises a nucleic acid encoding 4N. In some embodiments, the eulkaryotic organism comprises a nucleic acid encoding 40. In some embodiments, the eukaryotic organism comprises nucleic acids encoding 4B and 4D. In some embodiments, the eukaryotic organism comprises nucleic acids encoding 4E. 4C and 4D. In some embodiments, the eukaryotic organism comprises nucleic acids encoding 4E, 4F and 4G. In some embodiments, the eukaryotic organism comprises nucleic acids encoding 4L, 4F and 4G. In some embodiments, the eukaryotic organism comprises nucleic acids encoding 4HI, 4N and 4G. In some embodiments, the eukaryotic organism comprises nucleic acids encoding 4H and 4J. In some embodiments, the eukaryotic organism comprises nucleic acids encoding 41-1, 41 and 4G. In some embodiments, the eukaryotic organism comprises nucleic acids encoding 4L, 4F and 4G. In some embodiments, the eukaryotic organism comprises nucleic acids encoding 40, 4N and 4G. In some embodiments, the eukaryotic organism comprises nucleic acids encoding 4A, 4N and 4G. [002651 In another aspect, provided herein is a non-naturally eukaryotic organism comprising a 1,3-BDO pathway, wherein said organism further comprises one or more endogenous and/or exogenous nucleic acids encoding an attenuated 1,3-BDO pathway enzyme selected from the group consisting of 4B, 4C, 41), 4E, 4F, 4G, 4H, 41. 43, 4L, 4N and 40; wherein the attenuated 1,3-BDO pathway enzyme is NAPDH-dependent and has lower enzymatic activity as compared to the 1,3-BDO pathway enzyme encoded by an unaltered or wild-type nucleic acid. In some embodiments, the eukaryotic organism comprises a nucleic acid encoding 4B. In some embodiments, the eukaryotic organism comprises a nucleic acid encoding 4C. In some embodiments, the eukaryotic organism comprises a nucleic acid encoding 41). In some embodiments, the eukaryotic organism comprises a nucleic acid encoding 44E. In some embodiments, the eukaryotic organism comprises a nucleic acid encoding 4F. In some embodiments, the eukaryotic organism comprises a nucleic acid encoding 4G. In some embodiments, the eukaryotic organism comprises a nucleic acid encoding 4H. In some embodiments, the eukaryotic organism comprises a nucleic acid encoding 41. In some embodiments, the eukaryotic organism comprises a nucleic acid encoding 4J. In some -131embodiments, the eukaryotic organism comprises a nucleic acid encoding 4N. In some embodiments, the eukaryotic organism comprises a nucleic acid encoding 40. In some embodiments, the eukaryotic organism comprises nucleic acids encoding 4B and 4D. In some embodiments, the eulkaryotic organism comprises nucleic acids encoding 4E, 4C and 4D. In some embodiments, the eukaryotic organism comprises nucleic acids encoding 4E, 4F and 4G. In some embodiments, the eukaryotic organism comprises nucleic acids encoding 4L, 4F and 4G, In some embodiments, the eukaryotic organism comprises nucleic acids encoding 4H, 4N and 4G. In some embodiments, the eukaryotic organism comprises nucleic acids encoding 4H and 43, In some embodiments, the eukaryotic organism comprises nucleic acids encoding 41-1, 41 and 4G. In some embodiments, the eukaryotic organism comprises nucleic acids encoding 4L, 4F and 4G. In some embodiments, the eukaryotic organism comprises nucleic acids encoding 40, 4N and 4G. In some embodiments, the eukaryotic organism comprises nucleic acids encoding 4A, 4N and 4G. [002661 In another aspect, provided herein is a non-naturally eukaryotic organism comprising a 1,3-BDO pathway, wherein said organism further comprises one or more endogenous and/or exogenous nucleic acids encoding a 1,3-BDO pathway enzyme selected from the group consisting of 413, 4C, 41), 4E, 4F, 4G, 4H, 41, 4J, 4L, 4N, and 40; wherein at least one nucleic acid has been altered such that the 1,3-BDO pathway enzyme encoded by the nucleic acid has a lesser affinity for NADPH than the I,3-BDO pathway enzyme encoded by an unaltered or wild type nucleic acid. In some embodiments, the eukaryotic organism comprises a nucleic acid encoding 4B. in some embodiments, the eukaryotic organism comprises a nucleic acid encoding 4C. In some embodiments, the eukaryotic organism comprises a nucleic acid encoding 4D. In some embodiments, the eukarvotic organism comprises a nucleic acid encoding 4E. In some embodiments, the eukaryotic organism comprises a nucleic acid encoding 4F. In some embodiments, the eukaryotic organism comprises a nucleic acid encoding 4G. In some embodiments, the eukaryotic organism comprises a nucleic acid encoding 4[I. In some embodiments, the eukaryotic organism comprises a nucleic acid encoding 41. In some enibodi ments, the eukaryotic organism comprises a nucleic acid encoding 43. In some embodiments, the eukaryotic organism comprises a nucleic acid encoding 4N. In some embodiments, the eukaryotic organism comprises a nucleic acid encoding 40. In some -132embodiments, the eukaryotic organism comprises nucleic acids encoding 4B and 4D. In some embodiments, the eukaryotic organism comprises nucleic acids encoding 4E, 4C and 4D. In some embodiments, the eukaryotic organism comprises nucleic acids encoding 4E, 4F and 4G. In some embodiments, the eukaryotic organism comprises nucleic acids encoding 4L, 4F and 4G. In some embodiments, the eukaryotic organism comprises nucleic acids encoding 4H, 4N and 4G. In some embodiments, the eukaryotic organism comprises nucleic acids encoding 41- and 4J. In some embodiments, the eukaryotic organism comprises nucleic acids encoding 4H, 41 and 4G. In some embodiments, the eukaryotic organism comprises nucleic acids encoding 4L, 4F and 4G. In some embodiments, the eukaryotic organism comprises nucleic acids encoding 40, 4N and 4G. In som embodiments, the eukaryotic organism comprises nucleic acids encoding 4A, 4N and 4G. [00267] In another aspect, provided herein is a non-naturally occurring eukaryotic organism comprising a 1 ,3-BDO pathway wherein said organism further comprises one or more endogenous and/or exogenous nucleic acids encoding a 1,3-BDO pathway enzyme selected from the group consisting of 4B, 4C, 4D, 4E, 4F, 4G, 4H, 41, 4J, 4L, 4N and 40; wherein the eukaryotic organism comprises one or more gene disruptions that attenuate the activity of an endogenous NA DPI--dependent 1,3-B1DO pathway enzyme. [002681 Alternatively, in some embodiments, the eukaryotic organism comprises a 1,3-BDO pathway, wherein one or more of the 1,3-BDO pathway enzymes utilizes NADPH as the cofactor. Therefore, it can be beneficial to increase the production of NA DPH1 in these eukaryotic organisms to achieve greater yields of 1 ,3-BDO. Several approaches for increasing cytosolic production of NADPH can be implemented including channeling an increased amount of flux through the oxidative branch of the pentose phosphate pathway relative to wild-type, channeling an increased amount of flux through the Entner Doudoroff pathway relative to wild type, introducing a soluble or membrane-bound transhydrogenase to convert NAD-I to NADP[I, or employing NADP-dependent versions of the following enzymes: phosphorylating or non phosphorylating g I yceral dehyde-3 -phosphate dehydrogenase, pyruvate dehydrogenase, formate dehydrogenase, or acylating acetylaldehyde dehydrogenase. Methods for increasing cytosolic production of NADPH] can be augmented by eliminating or attenuating native NAD-dependent -133enzymes including glyceraldehyde-3 -phosphate dehydrogenase, pyruvate dehydrogenase, form ate dehydrogenase, or acylating acetylaldehyde dehydrogenase. Methods for engineering increased NADPH availability are described in Example IX. [002691 In another aspect provided herein, is a non-naturally eukaryotic organism comprising: (1) a 1,31-BDO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding an NADPH-dependent 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO; and (2) a pentose phosphate pathway, wherein said organism comprises at least one endogenous and,/or exogenous nucleic acid encoding a pentose phosphate pathway enzyme selected from the group consisting of glucose-6-phosphate dehydrogenase, 6-phosph ogluconolactonase, and 6 phosphogluconate dehydrogenase (decarboxylating). In certain embodiments, the organism further comprises a genetic alteration that increases metabolic flux into the pentose phosphate pathway. [00270] In another aspect provided herein, is a non-naturally eukaryotic organism comprising: (1) a 1,3-BDO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding an NADPH-dependent 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-3DO; and (2) an Entner Doudoroff pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding an Entner Doudoroff pathway enzyme selected from the group consisting of glucose-6-phosphate dehydrogenase, 6-phosphogluconolactonase, phosphogluconate dehydratase, and 2-keto-3 deoxygluconate 6-phosphate aldolase, In certain embodiments, the organism further comprises a genetic alteration that increases metabolic flux into the Entner Doudoroff pathway. [002711 In another aspect, provided herein is a non-naturally eukaryotic organism comprising a 1,3-BDO pathway, wherein said organism further comprises: (1) a I ,3-BDO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a NADPH-dependent 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3 BDO; and (2) an endogenous and/or exogenous nucleic acid encoding a soluble or membrane bound transhydrogenase, wherein the transhydrogenase is expressed at a sufficient level to con vert NA DH to NA DP-I. -134- [002721 In another aspect, provided herein is a non-naturally eukaryotic organism comprising: (1) a 1,3-43DO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a NADPH-dependent 1 3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO; and (2) an endogenous and/or exogenous nucleic acid encoding an NADP-dependent phosphorylating or non-phosphorylating glyceraldehyde-3 phosphate dehydrogen ase. [002731 In another aspect, provided herein is a non-naturally eukaryotic organism comprising: (1) a 1,3-BDO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a NADPH-dependent I 3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-3DO; and (2) an acetyl-CoA pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding an acetyl-CoA pathway enzyme expressed in a sufficient amount to increase NADPH in the organism; wherein the acetyl-CoA pathway comprises (i) an NADP-dependent pyruvate dehydrogenase; (ii) a pyruvate formate lyase and an NA DP-dependent formate dehydrogenase; (iii) a pyruvate:ferredoxin oxidoreductase and an NADPH:ferredoxin oxidoreductase; (iv) a pyruvate decarboxylase and an NADP-dependent acylating acetylaldehyde dehydrogenase; (v) a pyruvate decarboxylase, a NA DP-dependent acylating acetaldehyde dehydrogenase, an acetate kinase, and a phosphotransacetylase; or (vi) a pyruvate decarboxylase., an NADP-dependent acylating acetaldehyde dehydrogenase, and an acetyl-CoA synthetase. In one embodiment, the acetyl COA pathway comprises an NADP-dependent pyruvate dehydrogenase. In another embodiment, the acetyl-COA pathway comprises a pyruvate fornate lyase and an N-ADP-dependent forrnate dehydrogenase. In other embodiments, the acetyl-COA pathway comprises a pyru vate: ferredoxin oxidoreductase and an NADPH:ferredoxin oxidored uctase. In another embodiment, the acetvl-COA pathway comprises a pyruvate decarboxylase and an NADP dependent acylating acetylaidehyde dehydrogenase. In another embodiment. the acetyl-COA pathway comprises a pyruvate decarboxylase, a NADP-dependent acylating acetaldehyde dehydrogenase, an acetate kinase, and a phosphotransacetylase. In another embodiment, the acetyl-COA pathway comprises a pyruvate decarboxylase, an NADP-dependent acylating acetaldehyde dehydrogenase, and an acetyl-CoA synthetase. In another embodiment, the organism further comprises one or more gene disruptions that attenuate the activity of an -135endogenous NAD-dependant pyruvate dehydrogenase, NAD-dependent formate dehydrogenase, NADH:ferredoxin oxidoreductase, NAD-dependent acylating acetylaldehyde dehydrogenase, or NAD-dependent acylating acetaldehyde dehydrogenase. In some embodiments, the organism further comprising one or more gene disruptions that attenuate the activity of an endogenous NAD-dependant pyruvate dehydrogenase, NAD-dependent format dehydrogenase, NADH:ferredoxin oxidoreductase, NA D-dependent acylating acetylaldehyde dehydrogenase, or NAD-dependent acylating acetaldehyde dehydrogenase. [002741 In another aspect, provided herein is a non-naturally eukaryotic organism comprising: (1) a 1,3-BDO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a NADP-I-dependent 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO; and (2) one or more endogenous and/or exogenous nucleic acids encoding a NAD( P)H cofactor enzyme selected from the group consisting of phosphorylating or non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase; pyruvate dehydrogenase; formate dehydrogenase; and acylating acetylaldehyde dehydrogenase; wherein the one or more nucleic acids encoding a NAD(P )H cofactor enzyme has been altered such that the NAD(P)H cofactor enzyme encoded by the nucleic acid has a greater affinity for NADPH than the NAD(P)H cofactor enzyme encoded by an unaltered or wild-type nucleic acid. In one embodiment, the NAD(P)H cofactor enzyme is a phosphorylating or non-phosphorylating giyceraldehyde-3 -phosphate dehydrogenase. In another embodiment, the NAD(P)H cofactor enzyme is a pyruvate dehydrogenase. In another embodiment, the NAD( IP)H cofactor enzyme is a format dehydrogenase. In yet another embodiment, the NAD(P)H cofactor enzyme is an acylating acetylaldehyde dehydrogenase. [00275] In another aspect, provided herein is a non-naturally eukaryotic organism comprising a 1,3-BDO pathway, wherein said organism further comprises: (1) a 1,3-BDO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a NADPH dependent 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3 BDO; and (2) one or more endogenous and/or exogenous nucleic acids encoding a NAD(P)H cofactor enzyme selected from the group consisting of a phosphorylating or non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase; a pyruvate dehydrogenase; a formate -136dehydrogenase; and an acylating acetylaldehyde dehydrogenase; wherein the one or more nucleic acids encoding NAD(P)- cofactor enzyme nucleic acid has been altered such that the NAD(P)H cofactor enzyme that it encodes for has a lesser affinity for NADH than the NAD(P)H cofactor enzyme encoded by an unaltered or wild-type nucleic acid. In one embodiment, the NAD(P)H cofactor enzyme is a phosphorylating or non-phosphorylating glyceraldehyde-3 phosphate dehydrogenase. In another embodiment, the NAD(P)JH cofactor enzyne is a pyruvate dehydrogenase. In another embodiment, the NAD(P)-I cofactor enzyme is a formate dehydrogenase. In yet another embodiment, the NAD(P)H cofactor enzyme is an acylating acetylaidehyde dehydrogenase. 1002761 In one embodiment of the eukaryotic organisms provided above, the 1,343DO pathway comprises 4A, 4E, 4F and 4G. In another embodiment, the 1,3-BDO pathway comprises 4A, 4B and 4D. In other embodiments, the 1,3-BDO pathway comprises 4A, 4E, 4C and 4D. In some embodiments, the I,3-BDO pathway comprises 4A, 4H and 4J. In other embodiments, the 1,3-BDO pathway comprises 4A, 4H, 41 and 4G. In certain embodiments, the 1,3-BDO pathway comprises 4A, 4H, 4M, 4N and 4G. In another embodiment, the 1,3-BDO pathway comprises 4A, 4-K, 40,N and 4G. In yet another embodiment, the 1,3-BDO pathway comprises 4A, 4K, 4L, 4F and 4G. In another embodiment, the eukaryotic organism further comprises an acetyl-CoA pathway selected from the group consisting of: (i) 2A, 213 and 2D; (ii) 2 1 A, 2C and 2D; (iii) 2A, 2B, 21E and 2F; (iv) 2A, 2C, 2E and 2F; (v) 2A, 213, 2E, 2K, and 2L; (vi.) 2A, 2C, 2E 2K and 2L; (vii) 5A and 5B; (viii) 5A, 5C and 5D; (ix) 5E, 5F, 5C and 5D; (x) 5G and 5D; (xi) 6A, 6D and 6C; (xii) 613, 6E and 6C; (xiii) IA, 10B and IOC; (xiv) ION, 1011, 10B and 10C; (xv) ION, IOL, 1DM, 10B and 10C (xvi) IOA, 1013, 1OG and I0D; (xvii) ION, 10H, 1013, 10(G and IOD; (xviii) 10N, 1OL, 1OM, lOB, lOG and IOD; (xix) 10A, 1013, 10J, 10K and 101D; (xx) ION, 101-1, 1013, 10J, 10K and 101); (xxi) ION, IOL, 10M, 1013, 10J, 1 OK and IOD; (xxii) 10A, 1OF and IOD: (xxiii) 10N, 10H. 1OF and 10D; and (xxiv) ION, 1OL, 10M, 1OF and 101). [002771 In another embodiment of the eukaryotic organisms provided above, the 1,3-13DO pathway comprises 7E, 7F, 4E, 4F and 4G. In another embodiment, the 1,3-BDO pathway comprises 71E, 71F, 4B and 4D. In other embodiments, the 1,3-BDO pathway comprises 71E, 71F, -137- 4E, 4C and 4D. In some embodiments, the 1,3-BDO pathway comprises 7E, 7F, 4H and 4J. In other embodiments, the 1,3-3DO pathway comprises 7E, 7F, 41-1, 41 and 4G. In certain embodiments, the 1,3-BDO pathway comprises 7E, 7F, 41-1 4M, 4N and 4G. In another embodiment, the 1,3-BDO pathway comprises 7E, 7F, 4K, 40, 4N and 4G, In yet another embodiment, the 1,3-BDO pathway comprises 7E, 7F, 4K, 4L, 4F and 4G. In another embodiment, the eukaryotic organism further comprises an acetyl-CoA pathway selected front the group consisting of: (i) 2A, 213 and 21); (ii) 2A, 2C and 2D; (iii) 2A, 2B, 2E and 21-; (iv) 2A, 2C, 2E and 21; (v) 2A, 2B, 2E, 2K, and 2L; (vi.) 2A, 2C, 2E, 2K and 2L (vii) 5A and 5B; (viii) 5A, 5C and 5D; (ix) 5E, 5F, 5C and 5D; (x) 5G and 5D; (xi) 6A, 61) and 6C; (xii) 613, 6E and 6C; (xiii) IA, lOB and IOC; (xiv) ION, 10H. 1OB and 1OC; (xv) ION, 1OL, 1GM, lOB and IOC; (xvi) 10 A, 1013, lOG and 101D; (xvii) ION, 101-1, 10B, 10G and 10D; (xviii) 10N, 1 OL, 10M, 10B, lOG and 10D; (xix) lOA, 1 OB, IOJ, 10K and 10D; (xx) ION, 10H, 1013, 10], 10K and 1OD; (xxi) ION, IOL, 10M, 1OB, 10 J, 10K and 10 D; (xxii) IA, I0F and 10 D; (xxiii) ION, 10H, 1OF and 1OD; and (xxiv) ION, 1OL, 1GM, 10F and 10D. 1002781 4.5 Increase of redox ratio [002791 Synthesis of 1,3-BDO, in the cytosol of eukaryotic organisms requires the availability of sufficient carbon and reducing equivalents. Therefore, without being bound to any particular theory of operation, increasing the redox ratio of NAD(P)H to NAD(P) can help drive the 1,3 BDO pathway in the forward direction. Methods for increasing the redox ratio of NAD(P)H to NAD(P) include limiting respiration, attenuating or eliminating competing pathways that produce reduced byproducts, attenuating or eliminating the use of NADH by NADH dehydrogenases, and attenuating or eliminating redox shuttles between compartments. [002801 One exemplary method to provide an increased number of reducing equivalents, such as NAD(P)H, for enabling the formation of I,3-BDO is to constrain the use of such reducing equivalents during respiration. Respiration can be limited by: reducing the availability of oxygen, attenuating NADH dehydrogenases and/or cvtochrome oxidase activity, attenuating G3P dehydrogenase, and/or providing excess glucose to Crabtree positive organisms. -138- [002811 Restricting oxygen availability by culturing the non-naturally occurring eukaryotic organisms in a fermenter is one approach for limiting respiration and thereby increasing the ratio of NAD( P)H to NAD(P). The ratio of NAD(P)H/NAD(P) increases as culture conditions get more anaerobic, with completely anaerobic conditions providing the highest ratios of the reduced cofactors to the oxidized ones. For example, it has been reported that the ratio of NADH/NAD = 0.02 in aerobic conditions and 0.75 in anaerobic conditions in E. coli (de Graes et at, J Bacteriol 181:2351-57 (1999)). [002821 Respiration can also be limited by reducing expression or activity of NADH dehydrogenases and/or cytochrome oxidases in the cell under aerobic conditions. In this case, respiration will be limited by the capacity of the electron transport chain. Such an approach has been used to enable anaerobic metabolism of E. coli under completely aerobic conditions (Portnoy et at, A EM 74:7561-9 (2008)). S. cerevisiae can oxidize cytosolic NADH directly using external NADH dehydrogenases, encoded by NDE1 and NDE2. One such NADH dehydrogenase in Yarrowa lipolytica is encoded by NDH2 (Kerscher et at, JCell Sci 112:2347 54 (1999)). These and other NADH dehydrogenase enzymes are listed in the table below. TABLE 2 Protein GenBank ID GI number Organism NDEI NP 013865.1 6323794 Saccharomvcescerevis/ae s288c VE _____ _ NP 010198.1 632011_8 __charomces cereviisze s288c NDH2 AJ0068521 3718004 Yarrowia lipolytica AN_1 610074 XP 001392541.2 317030427 Aspergi lus niger AN 1 12462094 XP 001394893.2 317033119 Aspergil/us niger KLLA0E21891g XP 454942.1 50309857 K/uyveroinces [actis KLLA0C06336g XP 452480.1 50305045 Kuneronmces lactis NDE1 XP 720034.1 68471982 Cand/ida albicans E XP /1,986._1 68475826_ Candida a/c [002831 Cytochrome oxidases of Saccharonyces cerevisiae include the COX gene products. COX 1-3 are the three core subunits encoded by the mitochondrial genome, whereas COX4- 13 are encoded by nuclear genes. Attenuation or deletion of any of the cytochrome genes results in a decrease or block in respiratory growth (Hermann and Funes, Gene 354:43-52 (2005)). Cytochrome oxidase genes in other organisms can be inferred by sequence homology. -139- TABLE 3 Protein GenBank ID GI number Organism COl__ _CAA0982_4. 1 4160366 Saccharmvce cereisiaes288c COX2 CAA09845.1 4160387 Saccharomycees cerevisiae s288c COX3 CAA09846.1 4160389 Saccharomyces cerevisiae s288c COX4 _NP_0112 8. -________ 63221' _ __ S harovc es cerevigiae288_ COX5A NP 014346.1 6324276 Saccharomyces cerevisiae s288c COX5B NP_0121 55.1 6322080 Saccharomyces cerevisiae s288c COX6 NP 011918_1 6321842_ S7ccharomycey cerevisia 288_ COX7 NP 013983.1 6323912 Saccharomyces cerevisiaes288c COX8 NP 013499,1 6323427 Saccharomyces cerevisiae s288c COX9 NP 0102161 6320136 Saccharomgvces cerevisaegg8c COX12 NP 013139.1 6323067 Saccharonces cerevae s288c COX13 NP 011 324.1 6321247 Saccharomyces cerevisiae s288c [002841 In one aspect provided herein, is a. non-naturally eukaryotic organism comprising a 1,3-BDO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1 ,3-BDO, and wherein the organism: (i) comprises a disruption in a endogenous and/or exogenous nucleic acid encoding a NADH dehydrogenase; (ii) expresses an attenuated NADH dehydrogenase; and/or (iii) has lower or no NADH dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism. In one embodiment, the organism (i) comprises a disruption in a endogenous and/or exogenous nucleic acid encoding a NADH dehydrogenase; and (ii) expresses an attenuated NADH dehydrogenase. In another embodiment, the organism (i) comprises a disruption in a endogenous and/or exogenous nueieic acid encoding a NADH dehydrogenase; and (iii) has lower or no NADH dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism. In another embodiment, the organism (ii) expresses an attenuated NADI dehydrogenase; and (iii) has lower or no NADH dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism. In yet another embodiment, the organism (i) comprises a disruption in a endogenous and/or exogenous nucleic acid encoding a NADH dehydrogenase; (ii) expresses an attenuated NADH dehydrogenase; and (iii) has lower or no NADH dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism. -140- [002851 In another aspect, provided herein is a non-naturally eukaryotic organism comprising a 1,3-O131)( pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO, and wherein the organism: (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a cytochrome oxidase; (ii) expresses an attenuated cytochrome oxidase; and/or (iii) has lower or no cytochrome oxidase enzymatic activity as compared to a wild-type version of the eukaryotic organism. In one embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a cytochrome oxidase; and (ii) expresses an attenuated cytochrome oxidase. In another embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a cytochrone oxidase; and (iii) has lower or no cytochrome oxidase enzymatic activity as compared to a wild type version of the eukaryotic organism. In another embodiment, the organism (ii) expresses an attenuated cytochrom e oxidase; and (iii) has lower or no cytochrome oxidase enzymatic activity as compared to a wild-type version of the eukaryotic organism. In yet another embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a cytochrome oxidase; (ii) expresses an attenuated cytochrome oxidase; and (iii) has lower or no cytochrome oxidase enzymatic activity as compared to a wild-type version of the eukaryotic organism. 1002861 In certain embodiments, cytosolic NADH can also be oxidized by the respiratory chain via the G3P dehydrogenase shuttle, consisting of cytosolic NADH-linked G3P dehydrogenase and a membrane-bound G3P:ubiquinone oxidoreductase. The deletion or attenuation of G3P dehydrogenase enzymes will also prevent the oxidation of NADH for respiration. S. cereviszae has three G3P dehydrogenase enzymes encoded by GPDI and GDP2 in the cytosol and GUT2 in the mitochondrion. GPD2 is known to encode the enzyme responsible for the majority of the glycerol formation and is responsible for maintaining the redox balance under anaerobic conditions. (GPDI is primarily responsible for adaptation of S. cerevisiae to osmotic stress (Bakker et al., FES Microbiol Rev 24:15-37 (2001)). Attenuation of GPD1, GPD2 and/or GIUT2 will reduce glycerol formation. GPDI and GUT2 encode G3P dehydrogenases in Yarrowia hpolytica (Beopoulos et al, AEM 74:7779-89 (2008)). GPDI and GPD2 encode for -141- G3P dehydrogenases in S. ponbe. Similarly, G3P dehydrogenase is encoded by CTRG 02011 in Canclida tropicalis and a gene represented by GI:20522022 in Candida albicans. TABLE 4 Protein GenBank ID GI number Organism GPD1 CAA98582,1 1430995 Saccharonyes cerevisiae GPD2 NP 014582.1 6324513 _ _ ccaroces ere i isae GUT2 NP 012111.1 6322036 Sacchamynces cerevisae GPD1 CAA22119.1 6066826 Yarrowia lipolyinca GUT12 CAG83113.1 49646728 Yarrowla lipolvica GPDi CAA22 119.1 3873542 Schizosaccharomces poinbe GPiD2 C AA91239,1 1039342 Schizosaccharomy111ces pombe N 1 786014 XP 001389035.2 317025419__ sergws AN 1 1768134 XP 001397265.1 _ _45_ 1503 Asnergias ng KLLAOC04004g XP 452375.1 50304839 Kluveronyces lactis CTRG 02011 XP 002547704,1 255725550 Cnida Weoicais GPDI XP 714362.1 68483412 Cand/da albicans GPD2 XP 713824.1 68484586 Candid albicans [002871 In another aspect, provided herein is a non-naturally occurring eukaryotc organism comprising a 1,3-BDO pathway, wherein said organism comprises at least one exogenous nucleic acid encoding a 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO, wherein the non-naturally occurring eukaryotic organism comprises at least one endogenous and/or exogenous nucleic acid encoding a 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO, and wherein the organism: (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a G3P dehydrogenase; (ii) expresses an attenuated G3P dehydrogenase; (iii) has lower or no G3P dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism; and/or (iv) produces lower levels of glycerol as compared to a wild-type version of the eukaryotic organism. In one embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a G3P dehydrogenase; and (ii) expresses an attenuated G3P dehydrogenase. In another embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a G3P dehydrogenase; and (iii) has lower or no G3P dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism. In another embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid -142encoding a G3P dehydrogenase and (iv) produces lower levels of glycerol as compared to a wild type version of the eukaryotic organism. In another embodiment, the organism (ii) expresses an attenuated G3P dehydrogenase and (iii) has lower or no G3P3 dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism. In another ernbodirnent, the organism (ii) expresses an attenuated G3P dehydrogenase; and (iv) produces lower levels of glycerol as compared to a wild-type version of the eukaryotic organism. In another embodiment, the organism (iii) has lower or no G3P dehydrogenase enzymatic activity as compared to a wild type version of the eukaryotic organism; and (iv) produces lower levels of glycerol as compared to a wild-type version of the eukaryotic organism. In another embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a G3P dehydrogenase; (ii) expresses an attenuated G3P dehydrogenase; and (iii) has lower or no G3 P dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism. In another embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a G3P dehydrogenase; (ii) expresses an attenuated G3P dehydrogenase; and (iv) produces lower levels of glycerol as compared to a wild-type version of the eukaryotic organism. In yet another embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a G3P dehydrogenase; (ii) expresses an attenuated G3P dehydrogenase; (iii) has lower or no G3P dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism; and (iv) produces lower levels of glycerol as compared to a wild-type version of the eukaryotic organism. [00288] Additionally, in Crabtree positive organisms, fermentative metaboism can be achieved in the presence of excess of glucose. For example, S. cerevisiae makes ethanol even under aerobic conditions. The formation of ethanol and glycerol can be reduced/eliminated and replaced by the production of 1,3-BDO in a Crabtree positive organism by feeding excess glucose to the Crabtree positive organism. In another aspect provided herein is a method for producing 1,3-BDO, comprising culturing a non-naturally occurring eukaryotic organism under conditions and for a sufficient period of time to produce 1,3-BDO, wherein the eukaryotic organism is a Crabtree positive organism that comprises at least one exogenous nucleic acid encoding a I 3-BDO pathway enzyme and wherein eukarvotic organism is in a culture medium comprising excess glucose. -143- [002891 Preventing forniation of reduced fermentation byproducts can also increase the availability of both carbon and reducing equivalents for 1,3-BDO. Two key reduced byproducts under anaerobic and microaerobic conditions are ethanol and glycerol. Ethanol can be formed from py-ruvate in two enzymatic steps catalyzed by pyruvate decarboxylase and ethanol dehydrogenase. Glycerol can be formed from the glycolytic intermediate dihydroxyacetone phosphate by the enzymes G3P dehydrogenase and G3P phosphatase. Attenuation of one or more of these enzyme activities in the eukaryotic organisms provided herein can increase the yield of 1,3-BDO. Methods for strain engineering for reducing or eliminating ethanol and glycerol formation are described in further detail elsewhere herein. 1002901 The conversion of acetyl-CoA into ethanol can be detrimental to the production of 1,3 BDO because the conversion process can draw away both carbon and reducing equivalents from the 1,3-BDO pathway. Ethanol can be formed from pyruvate in two enzymatic steps catalyzed by pyruvate decarboxylase and ethanol dehydrogenase. Saccharonyces cerevisiae has three pyruvate decarboxylases (PDCI, PDC5 and PDC6) and two of them (PDCI, PDC5) are strongly expressed. Deleting two of these PDCs can reduce ethanol production significantly. Deletion of all three eliminates ethanol formation completely but also can cause a growth defect because of inability of the cells to form acetyl-CoA for biomass formation. This, however, can be overcome by evolving cells in the presence of reducing amounts of C2 carbon source (ethanol or acetate) (van Maris et al, AEM 69:2094-9 (2003)). It has also been reported that deletion of the positive regulator PDC2 of pyruvate decarboxylases P3DC1 and PDC5, reduced ethanol formation to ~10% of that made by wild-type (Hohmann et a], Mol Gen Gener 241:657-66 (1993)). Protein sequences and identifiers of PDC enzymes are listed in Example I. [002911 In another aspect, provided herein is a non-naturally eukaryotic organism comprising a 1,3-BDO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a 1,3-BO)( pathway enzyme expressed in a sufficient amount to produce 1,3-BDO, and wherein the organism: (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a pyruvate decarboxylase; (ii) expresses an attenuated pyruvate decarboxylase; (iii) has lower or no pyruvate decarboxylase enzymatic activity as compared to a wild-type version of the eukaryotic organism; and/or (iv) produces lower levels of ethanol from -144pyruvate as compared to a wild-type version of the eukarvotic organism. In one embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a pyruvate decarboxylase; and (ii) expresses an attenuated pyruvate decarboxylase. In another embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a pyruvate decarboxylase; and (iii) has lower or no pyruvate decarboxylase enzymatic activity as compared to a wild-type version of the eukaryotic organism. In another embodiment, the organism (ii) expresses an attenuated pyruvate decarboxylase; and (iv) produces lower levels of ethanol from pyruvate as compared to a wild-type version of the eukaryotic organism. In another embodiment, the organism (ii) expresses an attenuated pyruvate decarboxylase; and (iii) has lower or no pyruvate decarboxylase enzymatic activity as compared to a wild-type version of the eukaryotic organism. In another embodiment, the organism (ii) expresses an attenuated pyruvate decarboxylase; and (iv) produces lower levels of ethanol from pyruvate as compared to a wild-type version of the eukaryotic organism. In another embodiment, the organism (iii) has lower or no pyruvate decarboxylase enzymatic activity as compared to a wild-type version of the eukaryotic organism; and (iv) produces lower levels of ethanol from pyruvate as compared to a wild-type version of the eukaryotic organism. In another embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a pyruvate decarboxylase; (ii) expresses an attenuated pyruvate decarboxylase; and (iii) has lower or no pyruvate decarboxylase enzymatic activity as compared to a wild-type version of the eukaryotic organism. In another embodiment, the organism () comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a pyruvate decarboxylase; (iii) has lower or no pyruvate decarboxylase enzymatic activity as compared to a wild-type version of the eukaryotic organism; and (iv) produces lower levels of ethanol from pyruvate as compared to a wild-type version of the eukaryotic organism. In another embodiment, the organism (ii) expresses an attenuated pyruvate decarboxylase; (iii) has lower or no pyruvate decarboxylase enzymatic activity as compared to a wild-type version of the eukaryotic organism; and (iv) produces lower levels of ethanol from pyruvate as compared to a wild-type version of the eukaryotic organism. In yet another embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a pyruvate decarboxylase; (ii) expresses an attenuated pyruvate decarboxylase; (iii) has lower or no pyruvate decarboxylase enzymatic -145activity as compared to a wild-type version of the eukaryotic organism; and (iv) produces lower levels of ethanol from pyruvate as compared to a wild-type version of the eukaryotic organism. [002921 Alternatively, ethanol dehydrogenases that convert acetaldehyde into ethanol can be deleted or attenuated to provide carbon and reducing equivalents for the 1,3-BDO pathway. To date, seven alcohol dehydrogenases, A Dill-A DiVI, have been reported in S cerevisiae (de Smidt et al, FEMS Yeast Res 8:967-78 (2008)). ADHI (GI: 1419926) is the key enzyme responsible for reducing acetaldehyde to ethanol in the cytosol under anaerobic conditions. It has been reported that a yeast strain deficient in ADHI cannot grow anaerobically because an active respiratory chain is the only alternative path to regenerate NADH and lead to a net gain of ATP (Drewke et al, JiBacteriol 172:3909-17 (1990)). This enzyme is an ideal candidate for downregulation to limit ethanol production. ADH2 is severely repressed in the presence of glucose. In K. lactis, two NAD-dependent cytosolic alcohol dehydrogenases have been identified and characterized. These genes also show activity for other aliphatic alcohols. The genes ADHI (GI: 113358) and A DH- II (GI:51704293) are preferentially expressed in glucose grown cells (Bozzi et al, Biochim Biophys Acta 1339:133-142 (1997)). Cytosolic alcohol dehydrogenases are encoded by ADHI (GI:608690) in C. albicans, ADHI (GI:3810864) in'S. pombe, ADHI (GI:5802617) in Y. lipoiytica, ADHI (GI:2114038) and AD HU (Gl:2143328)in Pichia stipitis or Schejjersomzyces stpitis (Passoth et al, Yeast 14:1311-23 (1998)). Candidate alcohol dehydrogenases are shown the table below. TABLE S Protein GenBank ID GI number Organism SAH f BAA24528.1 2 L,815409 Candida parasi/osy AD _____ NP 0145551 6_24486 Sachcliaroiyces cerev;iaeg 2 8 8 r ADH2 NP 014032.1 6323961 Saccharomyces cerevisiae s288c AIDH3 NP 013800.1 632 729 Saccharomnyces cerevisiae s288c ADHf14 NP 011258.2 269970305 Saccharomyces cerevisiae s288c ADI-S (SFA1) NP 010113.1 6320033 Saccharonnces cerevisiae s288c ADH6 NP 0140511 6323980) Saccharomyces cerevisiae s288c ADH7 NP 010030.1 6319949 Saccharomnyces cerevisiae s288c edhp CAA446 14. 1 1 210 K! zn've romvces lardis ADH P20369.1 113358 Kiuvveromyces lactis ADH2 CAA45739.1 2833 Kluyveronces lactis D___ __P49384.2 -- ____ __ 15 04294 -_______ _ Kluv eroniv es lacts -146- [002931 In another aspect, provided herein is a non-naturally eukaryotic organism comprising a 1,3-13D pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a I,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO, and wherein the organism: (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding an ethanol dehydrogenase; (ii) expresses an attenuated ethanol dehydrogenase; (iii) has lower or no ethanol dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism; and/or (iv) produces lower levels of ethanol as compared to a wild-type version of the eukaryotic organism. In one embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding an ethanol dehydrogenase; and (ii) expresses an attenuated ethanol dehydrogenase. In another embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding an ethanol dehydrogenase; and (iii) has lower or no ethanol dehydrogenase enzymatic activity as cornpared to a wild-type version of the eukaryotic organism. In another embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding an ethanol dehydrogenase; and (iv) produces lower levels of ethanol as compared to a wild-type version of the eukaryotic organism. In another embodiment, tie organism (ii) expresses an attenuated ethanol dehydrogenase; and (iii) has lower or no ethanol dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism. In another embodiment. the organism (ii) expresses an attenuated ethanol dehydrogenase; and (iv) produces lower levels of ethanol as compared to a wild-type version of the eukarvotic organism. In another embodiment, the organism (iii) has lower or no ethanol dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism; and (iv) produces lower levels of ethanol as compared to a wild-type version of the eukaryotic organism. In another embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding an effianol dehydrogenase; (ii) expresses an attenuated etianol dehydrogenase; and (iii) has lower or no ethanol dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism. In another embodiment, tie organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding an ethanol dehydrogenase; (ii) expresses an attenuated ethanol dehydrogenase; and (iv) produces lower levels of ethanol as compared to a wild-type version of the eukaryotic organism. In another embodiment, the -147organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding an ethanol dehydrogenase; (iii) has lower or no ethanol dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism; and (iv) produces lower levels of ethanol as compared to a wild-type version of the eukaryotic organism. In another ernbodirnent, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding an ethanol dehydrogenase; (ii) expresses an attenuated ethanol dehydrogenase; (iii) has lower or no ethanol dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism; and (iv) produces lower levels of ethanol as compared to a wild-type version of the eukaryotic organism. 1002941 Yeast such as S. cerevisiae can produce glycerol to allow for regeneration of NAD(P) under anaerobic conditions. Glycerol is fonned from the glycolytic intermediate dihydroxyacetone phosphate by the enzymes G3P dehydrogenase and G3P phosphatase. Without being bound by a particular theory of operation, it is believed that attenuation or deletion of one or more of these enzymes can eliminate or reduce the formation of glycerol, and thereby conserve reducing equivalents for production of 1,3-BDO. Exemplary G3P dehydrogenase enzymes were described above. G3P phosphatase catalyzes the hydrolysis of G3P to glycerol. Enzymes with this activity include the glycerol-I-phosphatase (EC 3,1.3.21) enzymes of Saccharonyves cerevisiae (GPP] and GPP2), Candida albicans and Dunaleilla parva (Popp et al, Biotechnol Bioeng 100:497-505 (2008); Fan et al, FE1S Microbiol Lett 245:107-16 (2005)). The D. parva gene has not been identified to date. These and additional G3P phosphatase enzymes are shown in the table below. TABLE 6 Pro tein Genffank ID GI Numnber Orpeanismi GPP1 DAA08494.1 285812595 Saccharomyces cereisiae GPP2 NP_010984,1 6320905 Saccharomyces cerevisiae I GPT__ XP 717809. 1 68476319 Candida albicans K(LLA0C08217g XP 452565.1 50305213 Kluyveromyces actis KLIAOCI11 43g XP_452697.1 50305475 Kluyveroynnes lactis IA ATI 1 380074 XP 00139236.1 145239445 Asperual/his nteer- - ANI_ 1 444054 XP 001390913.2 317029125 Aspergslluf nigger -148- [002951 In another aspect, provided herein is a non-naturally occurring eukaryotic organism comprising a 1,3-BDO pathway, comprising at least one exogenous nucleic acid encoding a 1,3 BDO pathway enzyme expressed in a sufficient amount to produce 1 ,3-BDO, wherein the non naturally occurring eukaryotic organism comprises at least one endogenous and/or exogenous nucleic acid encoding a 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO, and wherein the organism: (I) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a G3P dehydrogenase; (ii) expresses an attenuated G3P dehydrogenase; (iii) has lower or no G3P dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism; and/or (iv) produces lower levels of glycerol as compared to a wild-type version of the eukaryotic organism. In one embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a G3P phosphatase; and (ii) expresses an attenuated G3P phosphatase. In another embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a G33P phosphatase; and (iii) has lower or no G3P phosphatase enzymatic activity as compared to a wild-type version of the eukaryotic organism. In another enibodinient, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a G3P phosphatase and (iv) produces lower levels of glycerol as compared to a wild-type version of the eukaryotic organism. In another embodiment, the organism (ii) expresses an attenuated G3P phosphatase and (iii) has lower or no G3P phosphatase enzymatic activity as compared to a wild type version of the eukaryotic organism. In another embodiment, the organism (ii) expresses an attenuated G3P phosphatase; and (iv) produces lower levels of glycerol as compared to a wild type version of the eukaryotic organism. In another embodiment, the organism (iii) has lower or no G3P phosphatase enzymatic activity as compared to a wild-type version of the eukaryotic organism; and (iv) produces lower levels of glycerol as compared to a wild-type version of the eukaryotic organism. In another embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a G3P phosphatase; (ii) expresses an attenuated G3P phosphatase; and (iii) has lower or no G3P phosphatase enzymatic activity as compared to a wild-type version of the eukarvotic organism. In another embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a G3P phosphatase; (ii) expresses an attenuated G3P phosphatase; and (iv) produces lower levels -149of glycerol as compared to a wild-type version of the eukaryotic organism. In yet another embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a G3P phosphatase; ii) expresses an attenuated G3P phosphatase; (iii) has lower or no G3P phosphatase enzymatic activity as compared to a wild-type version of the eukaryotic organism; and (iv) produces lower levels of glycerol as compared to a wild-type version of the eukaryotic organism. [002961 Another way to eliminate glycerol production is by oxygen-limited cultivation (Bakker et al, supra). Glycerol formation only sets in when the specific oxygen uptake rates of the cells decrease below the rate that is required to reoxidize the NADH formed in biosynthesis. [002971 In addition to the redox sinks listed above, palate dehydrogenase can potentially draw away reducing equivalents when it functions in the reductive direction. Several redox shuttles believed to be functional in S. cerevisiae utilize this enzyme to transfer reducing equivalents between the cytosol and the mitochondria. This transfer of redox can be prevented by eliminating malate dehydrogenase and/or malic enzyme activity. The redox shuttles that can be blocked by the elimination of mdh include (malate-asparate sh uttle, (ii) rnalate-oxaloacetate shuttle, and (iii) malate-pyruvate shuttle. Genes encoding malate dehydrogenase and malic enzymes are listed in the table below: TABLE 7 Protein GenBank ID Ci Number Organism MDH1 NP 0128381 6322765 charomyces cerevisiae AMDH2 NP 014515.2 116006499 | Saccharonces cerevisiae AfD13 NP_010205.1 6320125 | Sacchar.

2 onyces cerevisiae MAE] NP 012896.1 6322823 |Sacharomyces cerevisiae AIDHI XP 722674.1 68466384 Calndida albicans MDH2 XP_718638.1 68474530 'Candida albicans A1 XP 716669.1 68478574 Candida albicans KLLAUF25960g XP 456236A 50312405 Kluyveromyces lactis KLLAE18635g XP 454793.1 50309563 /Kh veronvces lactis KLL.4 (fE07j2i g XP 454288.1 50308571 K 7 merom ve latis YALIAD1 6 75 3p XP 502909.1 50550873 Yarrow 'ia lipolyica YALIOE18634p XP 504112.1 50553402 Yarrovia lpolytica ANT 1 268064 XP 0013913021 145237310 AseilLusz1 n-er AN 1 12134 XP 001396546.1 145250065 Asprllus niger AN_ 1_22 104 XP 001395105.2 317033225 AsperTillus niger -150- [00298] In another aspect, provided herein is a non-naturally eukaryotic organism comprising a I,3-13D pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO, and wherein the organism: (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a malate dehydrogenase; (ii) expresses an attenuated malate dehydrogenase; (iii) has lower or no malate dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism; and/or (iv) has an attenuation or blocking of a malate-asparate shuttle, a palate oxaloacetate shuttle, and/or a nialate-pyruvate shuttle. In one embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a inalate dehydrogenase; and (ii) expresses an attenuated malate dehydrogenase. In another embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a malate dehydrogenase; and (iii) has lower or no malate dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism. In another embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a palate dehydrogenase; and (iv) has an attenuation or blocking of a malate-asparate shuttle, a malate oxaloacetate shuttle, and/or a malate-pyruvate shuttle. In another embodiment, the organism (ii) expresses an attenuated inalate dehydrogenase; and (iii) has lower or no malate dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism. In another embodiment, the organism (ii) expresses an attenuated malate dehydrogenase; and (iv) has an attenuation or blocking of a malate-asparate shuttle, a malate oxaloacetate shuttle, and/or a malate-pyruvate shuttle. In another embodiment, the organism (iii) has lower or no malate dehydrogenase enzymatic activity as compared to a wild-type version of the eukarvotic organism; and (iv) has an attenuation or blocking of a malate-asparate shuttle, a malate oxaloacetate shuttle, and/or a malate-pyruvate shuttle. In another embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a malate dehydrogenase; (ii) expresses an attenuated malate dehydrogenase; and (iii) has lower or no malate dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism. In another embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a palate -151dehydrogenase; (ii) expresses an attenuated malate dehydrogenase; and (iv) has an attenuation or blocking of a malate-asparate shuttle, a malate oxaloacetate shuttle, and/or a malate-pyruvate shuttle. In another embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a malate dehydrogenase; (iii) has lower or no rnalate dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism; and (iv) has an attenuation or blocking of a malate-asparate shuttle, a inalate oxaloacetate shuttle, and/or a malate-pyruvate shuttle. In yet another embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a malate dehydrogenase; (ii) expresses an attenuated malate dehydrogenase; (iii) has lower or no malate dehydrogenase enzymatic activity as compared to a wild-type version of the eukarvotic organism; and (iv) has an attenuation or blocking of a malate-asparate shuttle, a malate oxaloacetate shuttle, and/or a malate-pyruvate shuttle. [002991 Overall, deletion of the aforementioned sinks for redox either individually or in combination with the other redox sinks will eliminate the use of reducing power for respiration or byproduct formation. It has been reported that the deletion of the external NADH dehydrogenases (NDE 1 and NDE2) and the mitochondrial G3P dehydrogenase (GUT2) almost completely eliminates cytosolic NAD+ regeneration in S. cerevisiae (Overkamp et al, J Bacteriol 182:2823-30 (2000)). [003001 In one embodiment of the eukaryotic organisms provided above, the 1.,3-BDO pathway comprises 4A, 4E, 4F and 4G. In another embodiment, the I ,3-BDO pathway comprises 4A, 4B and 4D. In other embodiments, the 1,3-BDO pathway comprises 4A, 4E, 4C and 4D. In some embodiments, the 1,3-BDO pathway comprises 4A, 4H and 4J. In other embodiments, the 1 ,3-BDO pathway comprises 4A, 4H, 41 and 4G. In certain embodiments, the 1,3-BDO pathway comprises 4A, 4H, 4M, 4N and 4G. In another embodiment, the 1,3-BDO pathway comprises 4A, 4K, 40, 4N and 4G. In yet another embodiment, the 1,3-BDO pathway comprises 4A, 4K. 4L. 4F and 4G. In another embodiment, the eukaryotic organism further comprises an acetyl-CoA pathway selected from the group consisting of: (i) 2A, 213 and 2D; (ii) 2A, 2C and 21); (iii) 2A, 2B, 2E and 2F; (iv) 2A, 2C, 2E and 2F; (v) 2A, 2B, 2E, 2K, and 2L; (vi.) 2A, 2C, 2E, 2K_ and 2L.; (vii) 5A and 5B; (viii) SA, 5C and 5D; (ix) 5E, 5F, 5C and SD; (x) -152- 5G and SD; (xi) 6A, 6D and 6C; (xii) 6B, 6E and 6C; (xiii) IGA, 1GB and 1OC; (xiv) ION, 10H, 101B and 10(C; (xv) ION, 1OL, 1GM, 10B and 10C; (xvi) IGA, 10B, 10G and 10GD; (xvii) ION, 10H, 10B, 1OG and 1OD; (xviii) ION, 1OL, 10M, lOB, 1OG and 1OD; (xix) 10A, 1OB, lOJ, 10K and 1OD; (xx) ION, 101], 1GB, 10J, 10K and IOD; (xxi) ION, 10L, 10M, lOB, 10J, 10K and 1OD; (xxii) 10A, lOF and 1OD; (xxiii) ION, 101-, 1OF and 10D; and (xxiv) ION, 1OL, 1GM, lOF and IOD. [003011 In one embodiment of the eukaryotic organisms provided above, the 1,3-BDO pathway comprises 7E, 7F, 4E, 4F and 4G. In another embodiment, the 1,3-3DO pathway comprises 1E. 7F, 4B and 4D. In other embodiments, the 1,3-BDO pathway comprises 7E. TB, 4E, 4C and 4D. In some embodiments, the 1,3 -BDO pathway comprises TB, 7F, 41H and 4.1. In other embodiments, the 1,3-BDO pathway comprises 7E, 7F, 4H, 41 and 4G. In certain embodiments, the 1,3-BDO pathway comprises 7E, 7F, 41-, 41, 4N and 4G. In another embodiment, the 1,3-BDO pathway comprises 7E, 7F, 4K, 40, 4N and 4G. In yet another embodiment, the 1,3-BDO pathway comprises 7E, 7, 4K, 4L, 4F and 4G. In another embodiment, the eukaryotic organism further comprises an acetyl-CoA pathway selected from the group consisting of (i) 2A, 2B and 2D; (ii) 2A, 2C and 2D; (iii) 2A, 2B, 2E and 2F; (iv) 2A, 2C, 2E and 2F; (v) 2A, 2B, 2E , 2K , and 2L; (vi.) 2A, 2C, 2E, 2K and 2L; (vii) 5A and 5B; (viii) 5A, 5C and SD; (ix) 5E. 5F, SC and 5D; (x) 5G and 5D; (xi) 6A. 6D and 6C; (xii) 6B, 6E and 6C; (xiii) IA, 10B and 10C; (xiv) ION, 10H-[, 1013 and 10C; (xv) ION, 1OL, 10M, 1013 and 10(; (xvi) IGA, lOB, 1OG and I0D; (xvii) ION, 10H, 10B, 1OG and IOD; (xviii) ION, lGL, 10M, 1GB, 1OG and IOD; (xix) I0A, 1OB, 10J, 1OK and IOD; (xx) ION, lOH, 10B, 10J, 10K and 1OD; (xxi) ION, 10L, 10M, 1OB, 10J, 10K and 1OD; (xxii) 10A, 1OB and 1OD; (xxiii) 1ON, 10H, lOF and IOD; and (xxiv) ION, IOL, 1GM, lOF and IOD. 4.6 Attenuation of competing byproduct production pathways [003021 In certain embodiments, carbon flux towards 1,3-BDO formation is improved by deleting or attenuating competing pathways. Typical fermentation products of yeast include ethanol and glycerol. The deletion or attenuation of these byproducts can be accomplished by approaches delineated above. -153- [003031 Additionally, in the 1,3-BDO pathway, some byproducts can be formed because of the non-specific enzymes acting on the pathway intermediates. For example, CoA hydrolases and CoA transferases can act on acetoacetyl-CoA and 3-hydroxybutyryl-CoA to form acetoacetate and 3-hydroxybutyrate respectively. Accordingly, in certain embodiments, deletion or attenuation of pathways acting on 1,3-BDO pathway intermediates within any of the non naturally occurring eukaryotic organisms provided herein can help to increase production of 1,3 BDO in these organisms. [003041 The conversion of 3-hydroxybutyryl-CoA to 3-hydroxybutyrate can be catalyzed by an enzyme with 3-hydroxybutyratyl-CoA transferase or hydrolase activity. Similarly, the conversion of acetoacetyl-CoA to acetoacetate can be catalyzed by an enzyme with acetoacetyl CoA transferase or hydrolase activity. These side reactions that divert 1,3-BDO pathway intermediates from 1,3-BDO production can be prevented by deletion or attenuation of enzymes with these activities. Exemplary CoA hydrolases and CoA transferases are shown in the table below. TABLE S Protein GeoBank ID __ number Organism Tes! NP 012553.1 6322 480 Saccharonyces cereavisia s288c 4 CH1 NP 009538.1 6319456 Saccharonyces cerevis/ae s288c Y JAUOF14729p XP 505426.1 50556036 Yarrowia lipolytica YALIOE3 096Sp XP 5046 13.1 505-5m4409 Yarroia hpo/vt/ca KLLA0E!6523g XP 454694.1 50309373 Khuveromyces lactis KLLA&E1056ig XP 454427.1 5-308845 Kluyveromvces lactis A CI 1 P83773.2 229462795 Candida albic-ns CaO19.10681 XP 714720.1 68482646 Candida albicans AN1 318184 XP_00140151 2.1 145256774 Aspergi//us niger ANY / 1594124 XP 00 1401252.2 1:317035188 Apr//sia tesB NP 414986.1 16128437 Escherichia coli [003051 In another aspect, provided herein is a non-naturally eukaryotic organism comprising a 1,3-BDO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a 1 ,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO, and wherein the organism: (I) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding an acetoacetyl-CoA hydrolase or transferase; (ii) expresses an -154attenuated acetoacetyl-CoA hydrolase or transferase; and/or (iii) has lower or no acetoacetvl CoA hydrolase or transferase enzymatic activity as compared to a wild-type version of the eukarvotic organism. In one embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding an acetoacetyl-CoA hydrolase or transferase; and (ii) expresses an attenuated acetoacetyl-CoA hydrolase or transferase. In another embodiment, the organisrn i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding an acetoacetyl- CoA hydrolase or transferase; and (iii) has lower or no acetoacetyl-CoA hydrolase or transferase enzymatic activity as compared to a wild-type version of the eukaryotic organism. In another embodiment, the organism (ii) expresses an attenuated acetoacetyl-CoA hydrolase or transferase; and (iii) has lower or no acetoacetyl-CoA hydrolase or transferase enzymatic activity as compared to a wild-type version of the eukaryotic organism. In yet another embodiment, the organism i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding an acetoacetyl-CoA hydrolase or transferase; (ii) expresses an attenuated acetoacetyl-CoA hydrolase or transferase; and (iii) has lower or no acetoacetyl-CoA hydrolase or transferase enzymatic activity as compared to a wild-type version of the eukaryotic organism. [003061 In another aspect, provided herein is a non-naturally eukaryotic organism comprising a 1,3-BDO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a I,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO, and wherein the organism: (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a 3-hydroxybutyryl-CoA hydrolase or transferase; (ii) expresses an attenuated 3-hydroxybutyryl-CoA hydrolase or transferase; and/or (iii) has lower or no 3-hydroxybutyryl-CoA hydrolase or transferase enzymatic activity as compared to a wild type version of the eukaryotic organism. In one embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a 3-hydroxybutyryl-CoA hydrolase or transferase; and (ii) expresses an attenuated 3-hydroxybutyryl-CoA hydrolase or transferase. In another embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding an 3-hydroxybutyryl-CoA hydrolase or transferase; and (iii) has lower or no 3-hydroxybutyryl-CoA hydrolase or transferase enzymatic activity as compared to a wild-type version of the eukaryotic organism. In another embodiment, the -155organism (ii) expresses an attenuated 3-hydroxybutyryl-CoA hydrolase or transferase; and (iii) has lower or no 3-hydroxybutyryl-CoA hydrolase or transferase enzymatic activity as compared to a wild-type version of the eukaryotic organism. In yet another embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a 3 hydroxybutyryl-CoA hydrolase or transferase; (ii) expresses an attenuated 3-hydroxybutyryl CoA hydrolase or transferase; and (iii) has lower or no 3-hydroxybutyryl-CoA hydrolase or transferase enzymatic activity as compared to a wild-type version of the eukaryotic organism. [003071 Non-specific native aldehyde dehydrogenases are another example of enzymes that acts on 1 5 3-BDO pathway intermediates. Such enzymes can, for example, convert acetyl-CoA into acetaldehyde or 3-hydroxybutyraldehyde to 3-hydroxybutyrate or 3-oxobutyraldehyde to acetoacetate. Acylating acetaldehyde dehydrogenase enzymes are described in Example I. Several Saccharoiyces cerevisiae enzyrnes catalyze the oxidation of aldehydes to acids including ALD 1 (ALD6), ALD2 and ALD3 (Navarro-Avino et al, Yeast 15:829-42 (1999); Quash et al, Biochem Pharrnacol 64:1279-92 (2002)). The mitochondrial proteins ALD4 and ALD5 catalyze similar transformations (Wang et al, J Bacteriol 180:822-30 (1998); Boubekeur et al, Eur J Biochem 268:5057-65 (2001)). Aldehyde dehydrogenase enzymes in E. coli that catalyze the conversion of acetaldehyde to acetate include YdcW, BetB, FeaB and AldA (Gruez et al, J Mol Biol 343:29-41 (2004); Yilmaz et al. Biotechnol Prog 18:1176-82 (2002) Rodriguez Zavala et al, Protein Sci 15: 1387-96 (2006)). Acid-forming aldehyde dehydrogenase enzymes are listed in the table below. TABLE 9 Protein GenBank ID GI number Organism ALD3 NP 013892.1 6323821 Saccharomyces cerevisiaes288c ALD4 NP 0150191 6324950 Saccharonyces cerevisiae s288c ALDS N 010996.2 330443526 Saceharonivees cerevv',iae g2M8c ALD6 NP 015264.1 6325196 Saccharomyces cerevisiae s288c H-FDI NP_013828.1 6323757 Saccharonvces cerevisiae s288c C(a 0 9.8 .561 ----------- XP 7 710976.1 68490403 Candfida albicans ---------------- CaO9. 742 XP 710989.1 68490378 Candida albicans Y4L10C03025 CA.G81682,1 49647250 Yarrowia lipolytica ANJ 1_1334164 XP 001398871.1 145255133 Aspergills niger AlM 1 223407_4 _P 001392964.2 31703 1176__ snrgiTusniger -156- A/VfI1226174 XP 001402476.1 145256256 4 7 ,e2'ai,~ nt1*1er ALDI P41751.1 1169291 Aspergius niger KLLA0D09999 CAH00602.1 49642640 Kluyve romyces lactis ydcw NP 415961.1 16129403 Escherichia col; be/B --------------- NP 414846.1 --------------i6128297 t- scbuu ihe colifeaB AAC74467.2 87081896 Escherichia coli aldA NP 415933.1 16129376 Escherhicha coli 1003081 In another aspect, provided herein is a non-naturally eukaryotic organism comprising a 1 .3-BDO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a 1 ,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO, and wherein the organism: (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding an acetaldehyde dehydrogenase (acylating); (ii) expresses an attenuated acetaldehyde dehydrogenase (acylating); and/or (iii) has lower or no acetaldehyde dehydrogenase (acylating) enzymatic activity as compared to a wild-type version of the eukarvotic organism. In one embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding an acetaldehyde dehydrogenase (acylating); and (ii) expresses an attenuated acetaldehyde dehydrogenase (acylating). In another embodiment the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding an acetaldehyde dehydrogenase (acylating); and (iii) has lower or no acetaldehyde dehydrogenase (acylating) enzymatic activity as compared to a wild-type version of the eukaryotic organism. In another embodiment the organism (ii) expresses an attenuated acetaldehyde dehydrogenase (acylating); and (iii) has lower or no acetaldehyde dehydrogenase (acylating) enzymatic activity as comipared to a wild-type version of the eukaryotic organism. In yet another embodiment the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding an acetaldehyde dehydrogenase (acylating); (ii) expresses an attenuated acetaldehyde dehydrogenase (acylating); and (iii) has lower or no acetaldehyde dehydrogenase (acylating) enzymatic activity as compared to a wild-type version of the eukaryotic organism. [003091 In another aspect, provided herein is a non-naturally eukaryotic organism comprising a 1,3-BDO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a 1,3-BD) pathway enzyme expressed in a sufficient amount to produce -157- I .3-BDO, and wherein the organism: (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a 3-hydroxybutyraldehyde dehydrogenase; (ii) expresses an attenuated 3-hydroxybutyraldehyde dehydrogenase; and/or (iii) has lower or no 3 hydroxybutyraidehyde dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism. In one embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding an 3-hydroxybutyraldehyde dehydrogenase; and (ii) expresses an attenuated 3-hydroxybutyraldehyde dehydrogenase. In another embodiment the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a 3-hydroxybutyraldehyde dehydrogenase; and (iii) has lower or no 3 hydroxybutyraldehyde dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism. In another embodiment the organism (ii) expresses an attenuated 3 hydroxybutyraldehyde dehydrogenase; and (iii) has lower or no 3-hydroxybutyraldehyde dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism. In yet another embodiment the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a 3-hydroxybutyraldehyde dehydrogenase; (ii) expresses an attenuated 3-hydroxybutyraldehyde dehydrogenase; and (iii) has lower or no 3 hydroxybutyraldehyde dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism. 1003101 In another aspect, provided herein is a non-naturally eukaryotic organism comprising a 1,3-BDO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO, and wherein the organism: (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a 3-oxobutyraldehyde dehydrogenase; (ii) expresses an attenuated 3-oxobutyraldehyde dehydrogenase; and/or (iii) has lower or no 3-oxobutyraldehyde dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism. In one embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding an 3-oxobutyraldehyde dehydrogenase; and (ii) expresses an attenuated 3-oxobutyraldehyde dehydrogenase. In another embodiment the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding a 3 oxobutyraldehyde dehydrogenase; and (iii) has lower or no 3-oxobutyraldehyde dehydrogenase -158enzymatic activity as compared to a wild-type version of the eukaryotic organism. In another embodiment the organism (ii) expresses an attenuated 3-oxobutyraldehyde dehydrogenase; and (iii) has lower or no 3-oxobutyraldehyde dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism, In yet another embodiment the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding an 3 oxobutyraldehyde dehydrogenase; (ii) expresses an attenuated 3-oxobutyraldehyde dehydrogenase; and (iii) has lower or no 3-oxobutyraldehyde dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism. [003111 Other enzymes that act on 1,3-BDO pathway intermediates include ethanol dehydrogenases that convert acetaldehyde into ethanol, as discussed above and 1,3-butanediol into 3-oxobutanol. A number of organisms encode genes that catalyze the interconversion of 3 oxobutanol and 1,3-butanediol, including those belonging to the genus Bacillus, Brevibacteriun, Candida, and Klebsiella, as described by Matsuyama et at. J 1 il Cat B Enz, 11:513-521 (2001). One of these enzymes, SADH from Candida parapsilosis, was cloned and characterized in . coli. A mutated Rhodococcus phenylacetaldehyde reductase (Sar268) and a Leijbnia alcohol dehydrogenase have also been shown to catalyze this transformation (Itoh et al., ApplI.Microbiol Biotechnol. 75:1249-1256 (2007)). These enzymes and those previously described for conversion of acetaldehyde to ethanol are suitable candidates for deletion and/or attenuation. Gene candidates are listed above. [003121 In another aspect, provided herein is a non-naturally eukaryotic organism comprising a 1,3-BDO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a 1,3-BDO pathway enzyme expressed in a sufficient amount to produce I ,3-BDO, and wherein the organism: (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding an ethanol dehydrogenase; (ii) expresses an attenuated ethanol dehydrogenase; and/or (iii) has lower or no ethanol dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism. In one embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding an ethanol dehydrogenase; and (ii) expresses an attenuated ethanol dehydrogenase. In another embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid -159encoding an ethanol dehydrogenase; and (iii) has lower or no ethanol dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism. In another ernbodimenr, the organism (ii) expresses an attenuated ethanol dehydrogenase; and (iiii) has lower or no ethanol dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism. In yet another embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding an ethanol dehydrogenase; (ii) expresses an attenuated ethanol dehydrogenase; and (iii) has lower or no ethanol dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism. In some embodiments, one or more other alcohol deydrogenases are used in place of the ethanol dehydrogenase. 1003131 In another aspect, provided herein is a non-naturally eukaryotic organism comprising a 1.3-BDO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1 ,3-BDO, and wherein the organism: (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding an 1,3-butanediol dehydrogenase; (ii) expresses an attenuated 1,3-butanediol dehydrogenase; and/or (iii) has lower or no 1,3-butanediol dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism. In one embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding an 1,3-butanediol dehydrogenase; and (ii) expresses an attenuated 1,3-butanediol dehydrogenase. In another embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding an 1,3-butanediol dehydrogenase; and (iii) has lower or no 1,3-butanediol dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism. In another embodiment, the organism (ii) expresses an attenuated 1I,3-butanediol dehydrogenase; and (iiii) has lower or no 1,3-butanediol dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism. In yet another embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding an 1,3-butanediol dehydrogenase; (ii) expresses an attenuated 1,3 -butanediol dehydrogenase; and (iii) has lower or no 1 ,3-butanediol dehydrogenase enzymatic activity as compared to a wild-type version of the eukaryotic organism. -160- [003141 In an organism expressing a 1,3-BDO pathway comprising an acetyl-CoA carboxylase and acetoacetvl-C oA synthase (7E17F), in some embodiments, it may be advantageous to delete or attenuate endogenous acetoacetyl-CoA thiolase activity. Acetoacetyl-CoA thiolase enzymes are typically reversible, whereas acetoacetyl-CoA synthase catalyzes an irreversible reaction. Deletion of acetoacetyl-CoA thiolase would therefore reduce backflux of acetoacetyl-CoA to acctyl-CoA and thereby improve flux toward the 1,3-BDO product. [003151 In another aspect, provided herein is a non-naturally eukaryotic organism comprising a 1,3-BDO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-13DO, and wherein the organism: (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding an acetoacetyl-CoA thiolase; (ii) expresses an attenuated acetoacetyl-CoA thiolase; and/or (iii) has lower or no acetoacetyl-CoA thiolase enzymatic activity as compared to a wild-type version of the eukaryotic organism. In one embodiment, the organism (I) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding an acetoacetyl-CoA thiolase; and (ii) expresses an attenuated 1 acetoacetyl-CoA thiolase. In another embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding an acetoacetyl-CoA thiolase; and (iii) has lower or no acetoacetvl-CoA thiolase enzymatic activity as compared to a wild-type version of the eukarvotic organism. In another embodiment, the organism (ii) expresses an attenuated acetoacetyl-CoA thiolase; and (iiii) has lower or no acetoacetyl-CoA thiolase enzymatic activity as compared to a wild-type version of the eukaryotic organism. In yet another embodiment, the organism (i) comprises a disruption in an endogenous and/or exogenous nucleic acid encoding an acetoacetyl CoA thiolase; (ii) expresses an attenuated acetoacetyi-CoA thiolase; and (iii) has lower or no acetoacetyl-CoA thiolase enzymatic activity as compared to a wild-type version of the eukaryotic organism. [003161 In one embodiment of the eukaryotic organisms provided above, the 1,3-BDO pathway comprises 4A, 4E, 4F and 4G. In another embodiment, the 1,3-3DO pathway comprises 4A, 4B and 4D. In other embodiments, the 1,3-BDO pathway comprises 4A, 4E, 4C and 4D. In some embodiments, the 1,3-BDO pathway comprises 4A, 41-1 and 4J. In other -161embodiments, the 1,3-BDO pathway comprises 4A, 4H, 41 and 4G. In certain embodiments, the 1,3-3D0 pathway comprises 4A, 41-I, 4M, 4N and 4G. In another embodiment, the 1,3-13D) pathway comprises 4A, 4K, 40, 4N and 4G. In yet another embodiment, the 1,3-13DO pathway comprises 4A, 4K, 4L, 4F and 4G. In another embodiment, the eukaryotic organism further comprises an acetvl-CoA pathway selected from the group consisting of: () 2A, 2B and 21); (ii) 2A, 2C and 2D; (iii) 2A, 213, 2E and 2F; (iv) 2A, 2C, 2E and 2F; (v) 2A, 213, 2E, 2K, and 2L; (vi.) 2A, 2C, 2E, 2K and 2L; (vii) 5A and 513; (viii) 5A, 5C and 5D; (ix) 51, SF, 5C and 5D; (x) 5G and 5D; (xi) 6A, 6D and 6C; (xii) 6B, 6E and 6C; (xiii) 0A, 101B and TOC; (xiv) ION, 10, 1013 and 10 C; (xv) ION, 10L, 10M, 1013 and 10C; (xvi) 10A, 1013, lOG and 101D; (xvii) ION, IOH, 10B, 10G and IOD; (xviii) ION, 1OL, 10M, 10B, TOG and IOD; (xix) lOA, 10B iOJ, 10K and 101); (xx) TON, 101H, 1013, 10., 10K and 10D; (xxi) ION, 10 L, 10 N/, 1013, 10., 10K and 10D; (xxii) 1OA, 10F and 10D; (xxiii) TON, IOH, TOF and 10D; and (xxiv) ION, 10L, 10M, 10F and 10D. [003171 In another embodiment of the eukaryotic organisms provided above, the I ,3-3DO pathway comprises 7E, 7F, 4E, 4F and 4G. In another embodiment, the 1,3-BDO pathway comprises 7E, 7F, 4B and 4D. In other embodiments, the 1,3-BDO pathway comprises 7E, 7F, 4E, 4C and 41). In some embodiments, the 1,3-131) pathway comprises 7E, 71, 41H and 4J. In other embodiments, the 1,3-BDO pathway comprises 7E. 7F, 4H, 41 and 4G. In certain embodiments, the 1,3-131 pathway comprises 7E, 71, 41-1, 4M, 4N and 4G. In another embodiment, the 1,3-BDO pathway comprises 7E, 7F, 4K, 40, 4N and 4G. In yet another embodiment, the 1,3-BDO pathway comprises 7E, 7,17 4K, 4L, 4F and 4G. In another embodiment, the eukaryotic organism further comprises an acetyl-CoA pathway selected from the group consisting of: (i) 2A, 2B and 21); (ii) 2A, 2C and 2D; (iii) 2A, 213, 2E and 2F; (iv) 2A, 2 1 C, 2E and 217; (v) 2A, 23, 2E, 2K, and 2L; (vi ) 2A, 2C, 2E, 2K and 2L; (vii) 5A and 513; (viii) 5A, SC and 5D; (ix) 5E, 5F, 5C and 5D; (x) 5G and 5D; (xi) 6A, 6D and 6C; (xii) 6B, 6E and 6C; (xiii) I CA, 1013 and 10C; (xiv) ION, 1OHl, 10B and I0C; (xv) ION, 10L, 10M, 1013 and 10C; (xvi) 10A, 1013, TOG and 10D; (xvii) ION, IOH, 10B, 10G and 10D; (xviii) TON, 1OL, 10M, 1013, lOG and LCD; (xix) lOA, 10B, i0J, 10K and LCD; (xx) ION, 1011, 101B, TOJ, 10K and 10D; (xxi) TON, 1OL, 1OM, 10B, IOJ, 10K and 10D; (xxii) lOA, TOF and 10D; (xxiii) TON, 10H, 1F and 10D; and (xxiv) ION, 10L, 10M, 101F and 10D, -162- 4.7 1,3-BDO Exportation [003181 In certain embodiments, 1,3-butanediol exits a production organism provided herein in order to be recovered and/or dehvdrated to butadiene. Examples of genes encoding enzymes that can facilitate the transport of 1,3-butanediol include glycerol facilitator protein homologs are provided in Example XI. [00319] In one aspect, provided herein is a non-naturally occurring eukaryotic organism comprising a 1,3-BDO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a I,3-BDO pathway enzyme expressed in a sufficient amount to produce 1 ,3-BDO; and wherein said organism further comprises an endogenous and/or exogenous nucleic acid encoding a 1,3-BDO transporter, wherein the nucleic acid encoding the 1,3-BD) transporter is expressed in a sufficient amount for the exportation of 1,3 BDO from the eukaryotic organism. [003201 In one embodiment of the eukaryotic organisms provided above, the 1.3-BDO pathway comprises 4A, 4E, 4F and 4G. In another embodiment, the 1,3-BDO pathway comprises 4A, 4B and 4D. In other embodiments, the 1,3-BDO pathway comprises 4A, 4E, 4C and 4D. In some embodiments, the 1,3-BDO pathway comprises 4A, 41 and 4J. In other embodiments, the 1,3-13DO pathway comprises 4A, 4H, 41 and 4G. In certain embodiments, the 1,3-BDO pathway comprises 4A, 41, 4M, 4N and 4G. In another embodiment, the 1,3-BDO pathway comprises 4A, 4K, 40, 4N and 4G. In yet another embodiment, the 1,3-BDO pathway comprises 4A, 4K. 4L. 4F and 4G. In another embodiment, the eukaryotic organism further comprises an acetyl-CoA pathway selected from the group consisting of: (i) 2A, 213 and 21D; (ii) 2A, 2C and 2D; (iii) 2A, 2B, 2E and 2F; (iv) 2A, 2C, 2E and 2F; (v) 2A, 213, 2E, 2K. and 2L; (vi.) 2A, 2C, 2E, 2K and 2.; (vii) 5A and 513; (viii) SA, 5C and 5D; (ix) 5E, 5F, 5C and SD; (x) 5G and 5D; (xi) 6A, 6D and 6C; (xii) 6B, 6E and 6C; (xiii) 10A, lOB and 10C; (xiv) ION, lOH, 10B and IOC; (xv) ION, 1OL, 10M, 10B and 1OC; (xvi) iGA, 10B, I0G and 10D; (xvii) ION, 10H, 10B, lOG and IOD; (xviii) ION, IOL, 10M, 1013, lOG and lOD; (xix) 10A, 10B, l0J, IK and IOD; (xx) IN IOH, 10B, I0J, 10K and l0D; (xxi) ION, 1OL, 10M, 10B, I0J, 10K and I GD; (xxii) I A, 10 and 10); (xxiii) ION, 101-I, 1 OF and I GD; and (xxiv) ION, I CL, 10M, IF and l0D. -163- [003211 In another embodiment of the eukaryotic organisms provided above, the 1,3-BDO pathway comprises 7E, 7F, 4E' 4F and 4G. In another embodiment, the 1,3-43DO pathway comprises 7E, 7F, 4B and 4D. In other embodiments, the 1,3-BDO pathway comprises 7E, 7F, 4E, 4C and 4D. In some embodiments, the 1,3-BDO pathway comprises TE, 7F, 41-1 and 4J. In other embodiments, the 1,30-BDO pathway comprises 7E, 7F, 4H, 41 and 4G. In certain embodiments, the 1,3-BDO pathway comprises 7E, 7, 41-, 4M, 4N and 4G, In another embodiment, the 1,3-BDO pathway comprises 7E, 7, 4K, 40, 4N and 4G. In yet another embodiment, the 1,3-BDO pathway comprises 7E, 7T, 4K, 4L, 4F and 4G. In another embodiment, the eukaryotic organism further comprises an acetyl-CoA pathway selected from the group consisting of: (i) 2A, 2B and 2D; (ii) 2 A 2C and 2D; (iii) 2A. 213, 2E and 2F; (iv) 2A, 2C, 2E and 2F; (v) 2A, 23, 2E, 2K, and 2L; (vi.) 2A, 2C, ,- 2K and 2L; (vii) 5A and 513; (viii) 5A, 5C and 5D; (ix) 5E, 5B, 5C and 513; (x) 5G and 5D; (xi) 6A, 6D and 6C; (xii) 613, 6E and 6C; (xiii) 10A, 10B and 10C; (xiv) 10N, 1011, 101B and 10C (xv) 10N, IOL, IOM, 1 OB and 10C; (xvi) I0A, 101B, lOG and 10D (xvii) ION, LOH, 10B, lOG and IOD; (xviii) ION, IOL, 1GM, 101B, lOG and 10D; (xix) IGA, 10B, IOJ, 10K and 10D; (xx) ION, I0H, 10B, 10J, 10K and IOD; (xxi) ION, 1OL, IOM, 1013, 101, 10K and 101D; (xxii) I0A, 10F and 10D; (xxiii) ION, 1011, 10F and 10D; and (xxiv) ION, 1OL, 10M, 10F and 10D. 4.8 Mitochondrial Production of 1,3-BDO [003221 In some embodiments, a eukaryotic organism provided herein is engineered to efficiently direct carbon and reducing equivalents into a mitochondrial I,3-13DO production pathway. One advantage of producing 1,3-BDO in the mitochondria is the naturally abundant mitochondrial pool of acetyl-CoA, the key 1,3-13DO pathway precursor. Efficient conversion of acetyl-CoA to 1,3-BDO in the mitochondria requires expressing I,3-BDO pathway enzymes in the mitochondria. It also requires an excess of reducing equivalents to drive the pathway forward. Exemplary methods for increasing the amount of reduced NAD(P)H in the mitochondria are similar to those employed in the cytosol and are described in further detail below. To further increase the availability of the acetyl-CoA precursor, pathways that consume acetyl-CoA in the mitochondria and cytosol can be attenuated as needed. If the 1.3-BDO product is not exported out of the mitochondria by native enzymes or by diffusion, expression of -164a heterologous 1,3-BDO transporter, such as the glycerol facilitator, can also improve 1 ,3-BDO production, [00323] In some embodiments, targeting genes to the mitochondria is be accomplished by adding a mitochondrial targeting sequence to pathway enzymes. Mitochondrial targeting sequences are well known in the art. For example, fusion of the mitochondrial targeting signal peptide from the yeast COX4 gene to valencene production pathway enzymes resulted in a mitochondrial valencene production pathway that yielded increased titers relative to the same pathway expressed in the cytosol (Farhi et al, A1et Eng 13:474-81 (201 1)), In one embodiment, the eukaryotic organism comprises a 1 ,3-BDO pathway, wherein said organism consists of 1,3-BDO pathway enzymes that are localized in the mitochondria of the eukaryotic organism. [003241 In other embodiments, levels of metabolic cofactors in the mitochondria are manipulated to increase flux through the 1 ,3-BDO pathway, which can further improve mitochondrial production of 1,3-BDO. For example, increasing the availability of reduced NAD(P)H can help to drive the 1,3-BDO pathway forward. This can be accomplished, for example, by increasing the supply of NAD(P)I in the mitochondria and/or attenuating NAD(P)H sinks. [003251 In eukaryotic cells, a significant portion of the cellular NAD pool is contained in the mitochondria (Di Lisa et aL, FEBS Lett 492:4-8 (2001)). Increasing the supply of mitochondrial NAD(P)H can be accomplished in different ways. Pyrimidine nucleotides are synthesized in the cytosol and must be transported to the mitochondria in the forn of NAD' by carrier proteins. The NAD carrier proteins of Saccharonyces cerevisiae are encoded by N DTI (GI: 6322185) and NDT2 (GI: 6320831) (Todisco et al, JiRiol Chei 281:1524-31 (2006)), Reduced cofactors such as NAD(P)-l are not transported across the inner mitochondrial membrane (von Jagow et al, Eur J Biochem 12:583-92 (1970); Lee et al, JMemnbr Biol 161:173-181 (1998)). NADH in the mitochondria is normally generated by the TCA cycle and the pyruvate dehydrogenase complex. NADPH is generated by the TCA cycle, and can also be generated from NADH if the organism expresses an endogenous or exogenous mitochondrial NADH transhydrogenase. NADH transhydrogenase enzyme candidates are described below. -165- TABLE 10 Protein GenBank ID GI number Organism A\TD Ti NP012260.1 6322185 Suechaiwnnescyi's ANI1 1592184 XP 001401484.2 317038471 Aspergilius niger CaJ7 0216 XP 888808,1 77022728 Candida altbicans yAL0IE16478- XP 504023.1 5 05 5122 6 Yarrowria Iivolyltra KLLAOD140 36 XP 453688.1 50307419 Kluyveromyces lactis [003261 Increasing the redox potential (NAD(P)H/NAD(P) ratio) of the mitochondria can be utilized to drive the ],3-BO)) pathway in the forward direction. Attenuation of mitochondrial redox sinks will increase the redox potential and hence the reducing equivalents available for ],3-BO1). Exemplary NAD(P)I-l consuming enzymes or pathways for attenuation include the TCA cycle, NADH dehydrogenases or oxidases, alcohol dehydrogenases and aldehyde dehydrogenases. [003271 The non-naturally occurring eukaryotic organisms provided herein can, in certain embodiments, be produced by introducing expressible nucleic acids encoding one or more of the enzymes or proteins participating in one or more 1,3-BDO or acetyl-CoA pathways. in some embodiments, the non-naturally occurring eukaryotic organisms provided herein can be produced by introducing expressible nucleic acids encoding one or more of the enzymes or proteins participating in one or more acetyl-CoA pathways and one or more 1,3-3DO pathways. Depending on the host eukaryotic organism chosen, nucleic acids for some or all of a particular acctyl-CoA pathway and/or 1,3-13DO can be expressed. In some embodiments, nucleic acids for some or all of a particular acetyl-CoA pathway are expressed. In other embodiments, the eukaryotic organism further comprises nucleic acids expressing some or all of a particular 1,3 BDO pathway. For example, if a chosen host is deficient in one or more enzymes or proteins for a desired pathway, then expressible nucleic acids for the deficient enzyme(s) or protein(s) are introduced into the host for subsequent exogenous expression. Alternatively, if the chosen host exhibits endogenous expression of some pathway genes, but is deficient in others, then an encoding nucleic acid is needed for the deficient enzyme(s) or protein(s) to achieve cytosolic acetyl-CoA production, or acetyl-CoA production in combination with 1,3-BDO production. Thus, in certain embodiments, a non-naturally occurring eukaryotic organism provided herein -166can be produced by introducing exogenous enzyme or protein activities to obtain a desired acetyl-CoA pathway and/or I,3-DO pathway. Alternatively, a desired acetyl-CoA pathway can be obtained by introducing one or more exogenous enzyme or protein activities that, together with one or more endogenous enzymes or proteins, allows for the transport of acetyl-CoA from a mitochondrion of the organism to the cytosol of the organism, production of cytosolic acetyl CoA. In other ernbodirnents, the organism further comprises a 1,3-BDO pathway that can be obtained by introducing one or more exogenous enzyme or protein activities that, together with one or more endogenous enzymes or proteins, allows for the production of 1,3-BDO in the organism. 1003281 Further genetic modifications described herein to facilitate and/or optimize I,3-BDO production, for example, manipulation of particular endogenous nucleic acids of interest in the host cell to attenuate or delete competing byproduct pathways and enzymes, can be performed by any method known to those skilled in the art and as provided, for instance, in Example X. [003291 Host eukaryotic organisms can be selected from, and the non-naturally occurring eukaryotic organisms generated in, for example, yeast, fungus or any of a variety of other eukaryotic applicable to fermentation processes. Exemplary yeasts or fungi include species selected from Saccharomyces cerevisiae, Schizosaccharonyces pombe, Knveromnyces lactis, Kuyvveromyces marxianus, Aspergillus terreus, Aspergillus niger, Pichia pastoris, Rhizopus arrhizus, Rhizobus orvyzae, Yarrowia ipolytica, and the like. It is understood that any suitable eukaryotic host organism caii be used to introduce metabolic and/or genetic modifications to produce a desired product. In certain embodiments, the eukaryotic organism is a yeast, such as Saccharoiyces cerevisiae. In some embodiments, the eukaryotic organism is a, fungus. [00330] Organisms and methods described herein with general reference to the metabolic reaction, reactant or product thereof, or with specific reference to one or more nucleic acids or genes encoding an enzyme associated with or catalyzing, or a protein associated with, the referenced metabolic reaction, reactant or product. Unless otherwise expressly stated herein, those skilled in the art will understand that reference to a reaction also constitutes reference to the reactants and products of the reaction. Similarly, unless otherwise expressly stated herein, reference to a reactant or product also references the reaction, and reference to any of these -167metabolic constituents also references the gene or genes encoding the enzymes that catalyze or proteins involved in the referenced reaction, reactant or product, Likewise, given the well known fields of metabolic biochemistry, enzymology and genomics, reference herein to a gene or encoding nucleic acid also constitutes a reference to the corresponding encoded enzyme and the reaction it catalyzes or a protein associated with the reaction as well as the reactants and products of the reaction. [003311 As disclosed herein, intermediates en route to 1,3-BDO can be carboxylic acids or CoA esters thereof, such as 4-hydroxy butyrate, 3-hydroxybutyrate, their CoA esters, as well as crotonyl-CoA. Any carboxylic acid intermediate can occur in various ionized forms, including fully protonated, partially protonated, and fully deprotonated forms. Accordingly, the suffix " ate," or the acid form, can be used interchangeably to describe both the free acid form as well as any deprotonated form, in particular since the ionized form is known to depend on the pH in which the compound is found. it is understood that carboxylate intermediates includes ester forms of carboxylate products or pathway intermediates, such as 0-carboxylate and S carboxylate esters. 0- and S-carboxylates can include lower alkyl, that is Cl to C6, branched or straight chain carboxylates. Some such 0- or S-carboxylates include, without limitation, methyl, ethyl, n-propyl, n-butyl, i-propyl, sec-butyl, and tert-butyl, pentyl, hexyl 0- or S-carboxylates, any of which can further possess an unsaturation, providing for example, propenyl, butenyl, pentyl, and hexenyl 0- or S-carboxylates. 0-carboxylates can be the product of a biosynthetic pathway. Exemplary 0-carboxylates accessed via biosynthetic pathways can include, without limitation, methyl 4-hydroxybutyrate, methy l-3 -hydroxybutyrate, ethyl 4-hydroxybutyrate, ethyl 3-hydroxybutyrate, n-propyl 4-hydroxybutyrate, and n-propyl 3-hydroxybutyrate. Other biosynthetically accessible 0-carboxylates can include medium to long chain groups, that is C7 C22, 0-carboxylate esters derived from fatty alcohols, such heptyl, octyl, nonyl, decyl, undecyl, lauryl, tridecyl, myristyl, pentadecyl, cetyl. palmitolyl, heptadecyl, stearyl, nonadecyl, arachidyl, heneicosyl, and behenyl alcohols, any one of which can be optionally branched and/or contain unsaturations. 0-carboxylate esters can also be accessed via a biochemical or chemical process, such as esterification of a free carboxylic acid product or transesterification of an 0- or S carboxylate. S-carboxylates are exemplified by CoA S-esters, cysteinyl S-esters, alkylthioesters, and various aryl and heteroaryl thioesters. -168- [003321 Depending on the 1,3-BDO biosynthetic pathway constituents of a selected host eukarvotic organism comprising an 1,3-BDO pathway, the non-naturally occurring organisms provided herein comprising a 1,3-BDO pathway can include at least one exogenously expressed 1,3-BDO pathway-encoding nucleic acid and up to all encoding nucleic acids for one or more 1,3-BDO biosynthetic pathways. For example, 1,3-BDO biosynthesis can be established in a host deficient in a pathway enzyme or protein through exogenous expression of the corresponding encoding nucleic acid. In a host deficient in all enzymes or proteins of a 1,3-13DO pathway, exogenous expression of all enzyme or proteins in the pathway can be included, although it is understood that all enzymes or proteins of a pathway can be expressed even if the host contains at least one of the pathway enzymes or proteins. For example. exogenous expression of all enzymes or proteins in a pathway for production of 1,3-BDO can be included. [00333] In addition, depending on the acetyl-CoA pathway constituents of a selected host eukaryotic organism, the non-naturally occurring eukaryotic organisms provided herein can include at least one exogenously expressed acetyi-CoA pathway-encoding nucleic acid and up to all encoding nucleic acids for one or more acetyl-CoA pathways. For example, mitochondrial and/or peroxisomal acetyl-CoA exportation into the cytosol of a host and/or increase in cytosolic acetyl-CoA in the host can be established in a host deficient in a pathway enzyme or protein through exogenous expression of the corresponding encoding nucleic acid. In a host deficient in all enzymes or proteins of an acetyl-CoA pathway, exogenous expression of all enzyme or proteins in the pathway can be included, although it is understood that all enzymes or proteins of a pathway can be expressed even if the host contains at least one of the pathway enzymes or proteins. For example, exogenous expression of all enzymes or proteins in a pathway for production of cytosolic acetyl-CoA can be included, such as a citrate synthase, a citrate transporter, a citrate/oxaloacetate transporter, a citrate/malate transporter, an ATP citrate lyase, a citrate lyase, an acetyl-CoA synthetase, an acetate kinase and phosphotransacetylase, an oxaloacetate transporter, a cytosolic malate dehydrogenase, a malate transporter a mitochondrial malate dehydrogenase; a pyruvate oxidase (acetate forming); an acetyl-CoA ligase or transferase; an acetate kinase; a phosphotransacetylase; a pyruvate decarboxylase; an acetaldehyde dehydrogenase; a pyruvate oxidase (acetyl-phosphate forming); a pyruvate dehydrogenase, a pyruvate:ferredoxin oxidoreductase or pyruvate fornate lyase; a acetaldehyde dehydrogenase -169- (acylating); a threonine aldolase; a mitochondrial acetvlcamitine transferase; a peroxisomal acetylcarnitine transferase; a cytosolic acetylcarnitine transferase; a mitochondrial acetyicarnitine translocase; a peroxisomal acetylcarnitine translocase; a PEP carboxylase; a PEP carboxykinase; an oxaloacetate decarboxylase; a malonate semialdehyde dehydrogenase (acetylating); an acetyl CoA carboxylase; a malonyl-CoA decarboxylase; an oxaloacetate dehydrogenase; an oxaloacetate oxidoreductase; a nalonyi-CoA reductase; a pyruvate carboxylase; a rnalonate semialdehyde dehydrogenase; a malonyl-CoA synthetase; a malonyl-CoA transferase; a malic enzyme a malate dehydrogenase; a malate oxidoreductase; a pyruvate kinase; or a PEP phosphatase;. 1003341 Given the teachings and guidance provided herein, those skilled in the art will understand that the number of encoding nucleic acids to introduce in an expressible form will, at least, parallel the acetyl-CoA pathway deficiencies of the selected host eukaryotic organism. Therefore, a non-naturally occurring eukaryotic organism provided herein can have one, two, three, four, five, six, seven, eight, nine, ten, up to all nucleic acids encoding the enzymes or proteins constituting an acetyl-CoA pathway disclosed herein. In some embodiments, the non naturally occurring eukaryotic organisms also can include other genetic modifications that facilitate or optimize production of cytosolic acetyl-CoA in the organism or that confer other useful functions onto the host eukaryotic organism. In addition, those skilled in the art will further understand that, in embodiments involving eukaryotic organisms comprising an acetyl CoA pathway and 1,3-BDO pathway, the number of encoding nucleic acids to introduce in an expressible fom will, at least, parallel the 1,3-BDO pathway deficiencies of the selected host eukaryotic organism. Therefore, a non-naturally occurring eukaryotic organism provided herein can have one, two, three, four, five, up to all nucleic acids encoding the enzymes or proteins constituting a 1,3-BD0 biosynthetic pathway disclosed herein. In some embodiments, the non naturally occurring eukaryotic organisms also can include other genetic modifications that facilitate or optimize 1,3-BDO biosynthesis or that confer other useful functions onto the host eukaryotic organism. One such other functionality can include, for example, augmentation of the synthesis of one or more of the 1,3-BDO pathway precursors such as acetyl-CoA, -170- [003351 Generally, a host eukaryotic organism is selected such that it produces the precursor of an acetyl-CoA pathway, either as a naturally produced molecule or as an engineered product that either provides dIe novo production of a desired precursor or increased production of a precursor naturally produced by the host eukaryotic organism. For example, mitochondrial acetyi-CoA is produced naturally in a host organism such as Saccharonvces cerevisiae. A host organism can be engineered to increase production of a precursor, as disclosed herein. In addition, a eukarvotic organism that has been engineered to produce a desired precursor can be used as a host organism and further engneered to express enzyntes or proteins of an acetyl-CoA pathway, and optionally a 1,3-13DO pathway. 1003361 In some embodiments, a non-naturally occurring eukaryotic organism provided herein is generated from a host that contains the enzymatic capability to synthesize cytosolic acetyl CoA. In this specific embodiment it can be useful to increase the synthesis or accumulation of an acetyl-CoA pathway product to, for example, drive acetyl-CoA pathway reactions toward cytosolic acetyl-CoA production. Increased synthesis or accumulation can be accomplished by, for example, overexpression of nucleic acids encoding one or more of the above-described acetyl-CoA pathway enzymes or proteins. Overexpression of the enzyme or enzymes and/or protein or proteins of the acetyl-CoA pathway can occur, for example, through exogenous expression of the endogenous gene or genes, or through exogenous expression of the heterologous gene or genes. Therefore, naturally occurring organisms can be readily generated to be non-naturally occurring eukaryotic organisms as provided herein, for example, producing cytosolic acetyl-CoA, through overexpression of one, two, three, four, five, six, seven, eight, nine or ten, that is, up to all nucleic acids encoding acetyl-CoA pathway enzymes or proteins. In addition, a non-naturally occurring organism can be generated by mnutagenesis of an endogenous gene that results in an increase in activity of an enzyme in the acetyl-CoA pathway. 1003371 In certain embodiments, wherein the eukaryotic organism comprises an acetvl-CoA pathway and 1,3-BDO pathway, the organism is generated from a host that contains the enzymatic capability to synthesize both acetyl-CoA and 1,3-BDO. In this specific embodiment it can be useful to increase the synthesis or accumulation of a cytosolic acetyl-CoA and/or 1,3 BDO pathway product to, for exam ple, drive 1,3-BDO pathway reactions toward 1,3-BDO -17 1production. Increased synthesis or accumulation can be accomplished by, for example, overexpression of nucleic acids encoding one or more of the above-described acetvl-CoA and/or l,3-BDO pathway enzymes or proteins. Overexpression of the enzyme or enzymes and/or protein or proteins of the acetyl-CoA and/or I .3-BDO pathways can occur, for example, through exogenous expression of the endogenous gene or genes, or through exogenous expression of the heterologous gene or genes. Therefore, naturally occurring organisms can be readily generated to be non-naturally occurring eukaryotic organisms provided herein, for example, producing 1,3 BDO, through overexpression of one, two, three, four, five, that is, up to all nucleic acids encoding ],3-BO)( biosynthetic pathway enzymes or proteins. In addition, a non-naturally occurring organism can be generated by mutagenesis of an endogenous gene that results in an increase in activity of an enzyme in the acetyl CoA and/or ],3-BO)( biosynthetic pathway. [00338] In particularly useful embodiments, exogenous expression of the encoding nucleic acids is employed. Exogenous expression confers the ability to custom tailor the expression and/or regulatory elements to the host and application to achieve a desired expression level that is controlled by the user. However, endogenous expression also can be utilized in other embodiments such as by removing a negative regulatory effector or induction of the gene's promoter when linked to an inducible promoter or other regulatory element. Thus, an endogenous gene having a naturally occurring inducible promoter can be up-regulated by providing the appropriate inducing agent, or the regulatory region of an endogenous gene can be engineered to incorporate an inducible regulatory element, thereby allowing the regulation of increased expression of an endogenous gene at a desired time. Similarly, an inducible promoter can be included as a regulatory element for an exogenous gene introduced into a non-naturally occurring eukaryotic organism. [003391 It is understood that, in certain embodiments, any of the one or more exogenous nucleic acids can be introduced into a eukaryotic organism to produce a non-naturally occurring eukaryotic organism provided herein. The nucleic acid(s) can be introduced so as to confer, for example, an acetyl-CoA pathway onto the organism, for example, by expressing a polypeptide(s) having the given activity that is encoded by the nucleic acid(s). The nucleic acids can also be introduced so as to further a I .3-BDO biosynthetic pathway onto the organism -Alternatively, -172encoding nucleic acids can be introduced to produce an intermediate organism having the biosynthetic capability to catalyze some of the required reactions to confer acetyl-CoA production or transport, or further 1,3-BDO biosynthetic capability. For example, a non naturally occurring organism having an acetyl-CoA pathway, either alone or in combination with a 1,3-BDO biosynthetic pathway, can comprise at least two exogenous nucleic acids encoding desired enzymes or proteins. For example, the non-naturally occurring eukaryotic organism can comprise at least two exogenous nucleic acids encoding a pyruvate oxidase (acetate forming) and an acetyl-CoA synthetase (Figure 5, steps A and B). Thus. it is understood that any combination of two or more enzymes or proteins of a biosynthetic pathway can be included in a non-naturally occurring organism provided herein. Similarly, it is understood that any combination of three or more enzymes or proteins of a biosynthetic pathway can be included in a non-naturally occurring organism of provided herein, and so forth, as desired, so long as the combination of enzymes and/or proteins of the desired biosynthetic pathway results in production of the corresponding desired product. For example, the non-naturally occurring eukaiyotic organism can comprise at least three exogenous nucleic acids encoding a pyruvate oxidase (acetate forming), an acetate kinase, and a phosphotransacetylase (Figure 5, steps A, C and D); or an acetoacetyl-CoA thiolase, an acetoacetyl-CoA reductase (ketone reducing), and a 3-hydroxybutyryl-CoA reductase (alcohol forming) (Figure 4, steps A, [H and .1). Similarly, any combination of four or more enzymes or proteins of a biosynthetic pathway as disclosed herein can be included in a non-naturally occurring eukaryotic organism provided herein, as desired, so long as the combination of enzymes and/or proteins of the desired biosynthetic pathway results in production of the corresponding desired product, For example, the non-naturally occurring eukaryotic organism can comprise at least four exogenous nucleic acids encoding citrate synthase, a citrate transporter, a citrate lyase and an acetyl-CoA synthetase (Figure 2, steps A. B, E and F); or an acetoacetyl-CoA thiolase, an acetoacetyl-CoA reductase (ketone reducing), a 3 hydroxybutyryl-CoA reductase (aldehyde forming), and 3-hydroxybutyraldehyde reductase (Figure 4, steps A, 1, 1 and G). Other individual pathways depicted in the figures are also contemplated embodiments of the compositions and methods provided herein. Similarly, it is understood that a non-naturally occurring eukaryotic organism can, for example, comprise at least six exogenous nucleic acids, with three exogenous nucleic acids encoding three acetyl-CoA -173pathway enzymes and three exogenous nucleic acids encoding three 1,3-BDO pathway enzymes. Other numbers and/or combinations of nucleic acids and pathway enzymes are likewise contemplated herein. [003401 In some embodiments, the eukaryotic organism comprises exogenous nucleic acids encoding each of the enzymes of an acetyl Co-A pathway provided herein. In other embodiments, the eukaryotic organism comprises exogenous nucleic acids encoding each of the enzymes of a 1,3-BDO pathway provided herein. In yet other embodiments, the eukarvotic organism comprises exogenous nucleic acids encoding each of the enzymes of an acetyl Co-A pathway provided herein, and the eukaryotic organism further comprises exogenous nucleic acids encoding each of the enzymes of a 1,3-BD() pathway provided herein. 1003411 In addition to the biosynthesis of cytosolic acetyl-CoA, either alone or in combination with I,3-BDO, as described herein, the non-naturally occurring eukaryotic organisms and methods provided herein also can be utilized in various combinations with each other and with other eukaryotic organisms and methods well known in the art to achieve product biosynthesis by other routes. For example, one alternative to produce cytosolic acetyl-CoA other than use of than cytosolic acetyl-CoA producers is through addition of another eukaryotic organism capable of converting an acetyl-CoA pathway intermediate to acetyi-CoA. One such procedure includes, for example, the culturing or fermenting of a eukaryotic organism that produces an acetyl-CoA pathway intermediate. The acetyl-CoA pathway intermediate can then be used as a substrate for a second eukaryotic organism that converts the acetyl-CoA pathway intermediate to cytosolic acetyl-CoA. The acetyl-CoA pathway intermediate can be added directly to another culture of the second organism or the original culture of the acetyl-CoA pathway intermediate producers can be depleted of these eukaryotic organisms by, for example, cell separation, and then subsequent addition of the second organism to the fermentation broth can be utilized to produce the final product without intermediate purification steps. 1003421 In other embodiments, wherein the non-naturally occurring eukaryotic organism further comprises a 1,3-BDO pathway, one potential alternative to produce 1,3-BDO other than use of the I,3-BDO producers is through addition of another eukaryotic organism capable of converting 1,3-BDO pathway intermediate to 1,3-BDO. One such procedure includes, for -174example, the fermentation of a eukaryotic organism that produces 1,3-BDO pathway intermediate. The 1,3-3DO pathway intermediate can then be used as a substrate for a second eukarvotic organism that converts the I 3-BDO pathway intermediate to 1,3-BDO. The 1,3 BDO pathway intermediate can be added directly to another culture of the second organism or the original culture of the 1,3-BDO pathway intermediate producers can be depleted of these eukaryotic organisms by, for example, cell separation, and then subsequent addition of the second organism to the fermentation broth can be utilized to produce the final product without intermediate purification steps. [003431 In other embodiments, the non-naturally occurring eukaryotic organisms and methods provided herein can be assembled in a wide variety of subpathways to achieve biosynthesis of, for example, cytosolic acetyl-CoA. In these embodiments, biosynthetic pathways for a desired product can be segregated into different eukaryotic organisms, arid the different eukaryotic organisms can be co-cultured to produce the final product. in such a biosynthetic scheme, the product of one eukaryotic organism is the substrate for a second eukaryotic organism until the final product is synthesized. For example, the biosynthesis of cytosolic acetyl-CoA can be accomplished by constructing a eukaryotic organism that contains biosynthetic pathways for conversion of one pathway intermediate to another pathway intermediate or the product. Alternatively, cytosolic acetvl-CoA also can be biosynthetically produced from eukaryotic organisms through co-culture or co-fermentation using two organisms in the same vessel, where the first eukaryotic organism produces a cytosolic acetyl-CoA intermediate and the second eukaryotic organism converts the intermediate to acetyl-CoA. [00344] In certain embodiments, wherein the non-naturally occurring eukaryotic organisms further comprise a 1,3-BDO pathway, the organisms and methods provided herein can be assembled in a wide variety of subpathways to achieve biosynthesis of acetyl-CoA and/or 1,3 BDO. In these embodiments, biosvnihetic pathways for a desired product provided herein can be segregated into different eukaryotic organisms, and the different eukaryotic organisms can be co cultured to produce the final product. In such a biosynthetic scheme, the product of one eukaryotic organism is the substrate for a second eukaryotic organism until the final product is synthesized. For example, the biosynthesis of 1,3-13DO can be accomplished by constructing a - 175eukaryotic organism that contains biosynthetic pathways for conversion of one pathway intermediate to another pathway intermediate or the product. Alternatively, ],3-BD) also can be biosynthetically produced from eukaryotic organisms through co-culture or co-fermentation using two organisms in the same vessel, where the first eukarvotic organism produces ,3-BDO intennediate and the second eukarvotic organism converts the intennediate to 1 ,3-BDO. Certain embodiments include any combination of acetyl-CoA and 1,3-BDO pathway components. [003451 Given the teachings and guidance provided herein, those skilled in the art will understand that a wide variety of combinations and permutations exist for the non-naturally occurring eukaryotic organisms and methods provided herein, together with other eukaryotic organisms, with the co-culture of other non-naturally occurring eukaryotic organisms having subpathways and with combinations of other chemical and/or biochemical procedures well known in the art to produce cytosolic acetyl-CoA, either alone or in combination with a 1,3 BDO. [003461 Sources of encoding nucleic acids for an acetyl-CoA pathway enzyme or protein can include, for example, any species where the encoded gene product is capable of catalyzing the referenced reaction. Similarly, sources of encoding nucleic acids for a 1,3-13D pathway enzyme or protein or a related protein or enzyme that affects 1,3-BDO production as described herein (e.g., 1,3-13D byproduct pathway enzymes) can include, for example, any species where the encoded gene product is capable of catalyzing the referenced reaction. Such species include both prokaryotic and eukaryotic organisms including, but not limited to, bacteria, including archaea and eubacteria, and eukaryotes, including yeast, plant, insect, animal, and mammal, including human. Exemplary species for such sources include, for example, Escherichia coli Acidamninococcusfermentans, Acinetobacter baylvi, Acinetobacter calcoaceticus, Aquikfx aeolicus, Arabidopsis thaliana, Archaeoglobusfiulgidus, Aspergillus niger, Aspergi/us terreus, Bacillus subtilis, Bos Taurus, Candida albicans, Candida tropicalis, Chlamyudomonas reinhardtii, Chlorobiun tepidum, Citrobacter koseri, Citrus junos, Clostrid/iul acetobutvlicun, Clostridium kluyveri, Clostridium saccharoperbuityacetonicuim, Cyanobium PCC7001, Desuifatibacilium alkenivorans, Dictvostelium discoideum, Fusobacteriuni nucleatum, Ha/oarcu/a mzarismortui, Homoe sapiens, Hvdrogenobacter thermophilus, Klebsie/la -176- Pneumoniae, K/uyveroYmces lactis, Lactobacilius brevis, Leuconostoc inesenteroides, M~etallosphaera secula, Methanothernobacter thermautotrophicus Mus musculus, Mycobacteriun avium, Mvcobacterun bovis, 1vcobacteriwn marinwn, lvcobacteriun siegm atis, Nicotiana tabacum, Nocardia iowensis, Onvctoigus cuniculus, Penicilliun chrysogenum, Pichia pastors, Porphy roionas gingiv alis, Porphiyronionas gingivals, Pseudomnonas aeruginos, Pseudiomonas putida, Pyrobaculun aerophium, Ralstonia eutropha, Rat/us norvegicus, Rhodobacter sphaeroides, Saccharomyces cerevisiae, Salmonella enteric, Salmonella typhinurium, Schizosaccharomyces pombe, Sulfolobus acidocaldarius, Sulblobus so//Maricus, Sul/blobus tokodaui, Thermoanaerobacter tengeongensis, Therinus thermophilus, Trvpanosoma brucei. Tsukanurella paurometabola, Yarrowia lipolytica, Zoogloea ramigera and Zvmomonas mobilis, as well as other exemplary species disclosed herein or available as source organisms for corresponding genes. However, with the complete genome sequence available for now more than 550 species (with more than half of these available on public databases such as the NCBI), including 395 eukaryotic organism genomes and a variety of yeast, fungi, plant, and mammalian genones, the identification of genes encoding the requisite cytosolic acetyl-CoA and/or 1,3-BDO biosynthetic activity for one or more genes in related or distant species, including for example, homologues, orthologs, paralogs and nonorthologous gene displacements of known genes, and the interchange of genetic alterations between organisms is routine and well known in the art. Accordingly, the metabolic alterations allowing biosynthesis of cytosolic acetyl-CoA and/or 1,3-BDO described herein with reference to a particular organism can be readily applied to other eukaryotic organisms alike. Given the teachings and guidance provided herein, those skilled in the art will know that a metabolic alteration exemplified in one organism can be applied equally to other organisms. 1003471 In some instances, such as when an alternative cytosolic acetyl-CoA and/or 1,3-BDO biosynthetic pathway exists in an unrelated species, the cytosolic acetyl-CoA and/or 1,3-BDO biosynthesis can be conferred onto the host species by, for example, exogenous expression of a paralog or paralogs from the unrelated species that catalyzes a similar, yet non-identical metabolic reaction to replace the referenced reaction. Because certain differences among metabolic networks exist between different organisms, those skilled in the art will understand that the actual gene usage between different organisms can differ. However, given the teachings -177and guidance provided herein, those skilled in the art also will understand that the teachings and methods provided herein can be applied to all eukaryotic organisms using the cognate metabolic alterations to those exemplified herein to construct a eukaryotic organism in a species of interest that will synthesize cytosolic acetyl-CoA, either alone or in combination with 1,3-BDO. [003481 Methods for constructing and testing the expression levels of a non-naturally occurring cytosolic acetyl-CoA producing host can be performed, for example, by recombinant and detection methods well known in the art. Methods for constructing and testing the expression levels of a non-naturally occurring 1,3-131)0-producing host can also be performed, for example, by recombinant and detection methods well known in the art. Such methods can be found described in, for example, Sambrook et al., Molecular Clonina: A Laboratorv Manual, Third Ed., Cold Spring Harbor Laboratory, New York (2001); and Ausubel eti al., Current Protocols in Molecular Biology, John Wiley and Sons, Baltimore, MD (1999). [00349] Exogenous nucleic acid sequences involved in a pathway for production of cytosolic acetyl-CoA can be introduced stably or transiently into a host cell using techniques well known in the art including, but not limited to, conjugation, electroporation, chemical transformation, transduction, transfection, and ultrasound transformation. In embodiments, wherein the eukaryotic organism further comprises a 1,3-BDO pathway, exogenous nucleic acid sequences involved in a pathway for production of 1,3-BDO can also be introduced stably or transiently into a host cell using these same techniques. For exogenous expression in yeast or other eukaryotic cells, genes can be expressed in the cytosol without the addition of leader sequence, or can be targeted to mitochondrion or other organelies, or targeted for secretion, by the addition of a suitable targeting sequence such as a mitochondrial targeting or secretion signal suitable for the host cells. Thus, it is understood that appropriate modifications to a nucleic acid sequence to remove or include a targeting sequence can be incorporated into an exogenous nucleic acid sequence to impart desirable properties. Furthermore, genes can be subjected to codon optimization with techniques well known in the art to achieve optimized expression of the proteins. [00350] An expression vector or vectors can be constructed to include one or more cytosolic acetyl-CoA biosynthetic pathway encoding nucleic acids as exemplified herein operably linked -178to expression control sequences functional in the host organism. An expression vector or vectors can also be constructed to include one or more I,3-BDO biosynthetic pathway encoding nucleic acids as exemplified herein operably linked to expression control sequences functional in the host organism. Expression vectors applicable for use in the eukaryotic host organisms provided herein include, for example, plasmids, phage vectors, viral vectors, episomes and artificial chromosomes, including vectors and selection sequences or markers operable for stable integration into a host chromosome. Additionally, the expression vectors can include one or more selectable marker genes and appropriate expression control sequences. Selectable marker genes also can be included that, for example, provide resistance to antibiotics or toxins, complement auxotrophic deficiencies, or supply critical nutrients not in the culture media. Expression control sequences can include constitutive and inducible promoters, transcription enhancers, transcription terminators, and the like which are well known in the art. When two or more exogenous encoding nucleic acids are to be co-expressed, both nucleic acids can be inserted, for example, into a single expression vector or in separate expression vectors. For single vector expression, the encoding nucleic acids can be operationally linked to one common expression control sequence or linked to different expression control sequences, such as one inducible promoter and one constitutive promoter. The transformation of exogenous nucleic acid sequences involved in a metabolic or synthetic pathway can be confirmed using methods well known in the art. Such methods include, for example, nucleic acid analysis such as Northern blots or polymerase chain reaction (PCR-) amplification of mRNA, or immunoblotting for expression of gene products, or other suitable analytical methods to test the expression of an introduced nucleic acid sequence or its corresponding gene product. It is understood by those skilled in the art that the exogenous nucleic acid is expressed in a sufficient amount to produce the desired product, and it is further understood that expression levels can be optimized to obtain sufficient expression using methods well known in the art and as disclosed herein. [003511 In some embodiments, provided herein is a method for producing cytosolic acetyl CoA in a non-naturally occurring eukaryotic organism comprising an acetyl-CoA pathway comprising culturing any of the non-naturally occurring eukaryotic organisms comprising an acetyl-CoA pathway described herein under sufficient conditions for a sufficient period of time to produce cytosolic acetyl-CoA. In other embodiments, provided herein is a method for -179producing 1,3-BDO in a non-naturally occurring eukaryotic organism comprising an acetyl-CoA pathway and a I,3-BDO pathway, comprising culturing any of the non-naturally occurring eukarvotic organisms comprising an 1,3-BDO pathway described herein under sufficient conditions for a sufficient period of time to produce cytosolic acetyl-CoA and I,3-BDO. [003521 Suitable purification and/or assays to test for the production of cytosolic acetvl-CoA and/or 1,3-BDO can be performed using well known methods. Suitable replicates such as triplicate cultures can be grown for each engineered strain to be tested. For example, product and byproduct formation in the engineered production host can be monitored. The final product and intermediates, and other organic compounds, can be analyzed by methods such as HPLC (UHigh Performance Liquid Chromatography), GC-MS (Gas Chromatography-Mass Spectroscopy) and LC-MS (Liquid Chromatography-Mass Spectroscopy) or other suitable analytical methods using routine procedures well known in the art. The release of product in the fennentation broth can also be tested with the culture supernatant. Byproducts and residual glucose can be quantified by HPLC using, for example, a refractive index detector for glucose and alcohols, and a UV detector for organic acids (Lin et al., Biotechnol. Bioeng. 90:775-779 (2005)), or other suitable assay and detection methods well known in the art. The individual enzyme or protein activities from the exogenous DNA sequences can also be assayed using methods well known in the art. An increase in the availability of cytosolic acetyl-CoA can be demonstrated by an increased production of a metabolite that is formed form cytosolic acetyl CoA (e.g., 1-3-butanediol). Alternatively, functional cytosolic acetyl-COA pathways can be screened using an organism (e.g., S cerevis'iae) engineered so that it cannot synthesize sufficient cytosolic acetyl-CoA to support growth on minimal media. See WO/2009/013159. Growth on minimal media is restored by introducing a functional non-native mechanism into the organism for cytosolic acetyl-CoA production. 1003531 The cytosolic acetyl-CoA and/or 1,3-13DO can be separated from other components in the culture using a variety of methods well known in the art. Such separation methods include. for example, extraction procedures as well as methods that include continuous liquid-liquid extraction, pervaporation, membrane filtration, membrane separation, reverse osmosis, electrodialysis, distillation, crystallization, centrifugation, extractive filtration, ion exchange -180chromatography, size exclusion chromatography, adsorption chromatography, and ultrafiltration. All of the above methods are well known in the art, [00354] Any of the non-naturally occurring eukaryotic organisms described herein can be cultured to produce and/or secrete the biosynthetic products provided herein. For example, the cytosolic acetyl-CoA producers can be cultured for the biosynthetic production of cytosolic acetyl-CoA and or 1,3-BDO. 100355] For the production of cytosolic acetyl-CoA and/or 1,3-BDO, the recombinant strains are cultured in a medium with carbon source and other essential nutrients. It is sometimes desirable and can be highly desirable to maintain anaerobic conditions in the fermenter to reduce the cost of the overall process. Such conditions can be obtained, for example, by first sparging the medium with nitrogen and then sealing the flasks with a septum and crimp-cap. For strains where growth is not observed anaerobically, microaerobic or substantially anaerobic conditions can be applied by perforating the septum with a small hole for limited aeration. Exemplary anaerobic conditions have been described previously and are well-known in the art. Exemplary aerobic and anaerobic conditions are described, for example, in United State publication 2009/0047719, filed August 10, 2007. Fermentations can be performed in a batch, fed-batch or continuous manner, as disclosed herein. [003561 If desired, the pH of the medium can be maintained at a desired pH, in particular neutral p1, such as a pH of around 7 by addition of a base, such as NaOH or other bases, or acid, as needed to maintain the culture medium at a desirable pH. The growth rate can be determined by measuring optical density using a spectrophotometer (600 nm), and the glucose uptake rate by monitoring carbon source depletion over time. 1003571 In addition to renewable feedstocks such as those exemplified above, the eukaryotic organisms provided herein also can be modified for growth on syngas as its source of carbon. In this specific embodiment, one or more proteins or enzymes are expressed in the eukaryotic organisms to provide a metabolic pathway for utilization of syngas or other gaseous carbon source. -181- [003581 Organisms provided herein can utilize, and the growth medium can include, for example, any carbohydrate source which can supply a source of carbon to the non-naturally occurring eukaryotic organism. Such sources include, for example, sugars such as glucose, xylose, arabinose, galactose, rnannose, fructose, sucrose and starch. Other sources of carbohydrate include, for example, renewable feedstocks and biomass. Exemplary types of biomasses that can be used as feedstocks in the methods provided herein include cellulosic biomass, hemicellulosic biomass and lignin feedstocks or portions of feedstocks. Such biomass feedstocks contain, for example, carbohydrate substrates useful as carbon sources such as glucose, xylose, arabinose, galactose, mannose, fructose and starch. Given the teachings and guidance provided herein, those skilled in the art will understand that renewable feedstocks and biomass other than those exemplified above also can be used for culturing the eukaryotic organisms provided herein for the production of cytosolic acetyl-CoA and/or 1,3-BDO. [003591 In addition to renewable feedstocks such as those exemplified above, the eukaryotic organisms provided herein also can be modified for growth on syngas as its source of carbon. In this specific embodiment, one or more proteins or enzymes are expressed in the cytosolic acetyl CoA producing organisms to provide a metabolic pathway for utilization of syngas or other gaseous carbon source. [003601 Synthesis gas, also known as syngas or producer gas, is the major product of gasification of coal and of carbonaceous materials such as biomass materials, including agricultural crops and residues, Syngas is a mixture primarily of 1-12 and CO and can be obtained from the gasification of any organic feedstock, including but not limited to coal, coal oil, natural gas, biomass, and waste organic matter. Gasification is generally carried out under a high fuel to oxygen ratio. Although largely H2 and CO, syngas can also include CO2 and other gases in smaller quantities. Thus, synthesis gas provides a cost effective source of gaseous carbon such as CO and, additionally, C02. 1003611 Accordingly, given the teachings and guidance provided herein, those skilled in the art will understand that a non-naturally occurring eukaryotic organism can be produced that secretes the biosynthesized compounds provided herein when grown on a carbon source such as a carbohydrate. Such compounds include, for example, cytosolic acetyl-CoA and any of the -182intermediate metabolites in the acetyl-CoA pathway. Such compounds canals include, for example, 1,3-BDO and any of the intermediate metabolites in the 1,3-BDO pathway. All that is required is to engineer in one or more of the required enzyme or protein activities to achieve biosynthesis of the desired compound or intermediate including, for example, inclusion of some or all of the cytosolic acetyl-CoA and/or I,3-BDO biosynthetic pathways. Accordingly, in some embodiments, provided herein is a non-naturally occurring eukaryotic organism that produces and/or secretes cytosolic acetyl-CoA when grown on a carbohydrate or other carbon source and produces and/or secretes any of the intermediate metabolites shown in the acetyl-CoA pathway when grown on a carbohydrate or other carbon source. The cytosolic acetyl-CoA producing eukaryotic organisms provided herein can initiate synthesis from an intermediate, for example, citrate and acetate. In other embodiments, provided herein is a non-naturally occurring eukaryotic organism that produces and/or secretes 1,3-BDO when grown on a carbohydrate or other carbon source and produces and/or secretes any of the intermediate metabolites shown in the 1,3-BDO pathway when grown on a carbohydrate or other carbon source. The 1.3-BDO producing organism can initiate synthesis of 1,3-BDO from acetyl-CoA, and, as such, a combination of pathways is possible. [003621 The non-naturally occurring eukaryotic organisms provided herein are constructed using methods well known in the art as exemplified herein to exogenously express at least one nucleic acid encoding an acetyl-CoA pathway enzyme or protein in sufficient amounts to produce cytosolic acetyl-CoA. It is understood that the eukaryotic organisms provided herein are cultured under conditions sufficient to produce cytosolic acetyl-CoA. Following the teachings and guidance provided herein, the non-naturally occurring eukaryotic organisms provided herein can achieve biosynthesis of cytosolic acetyl-CoA resulting in intracellular concentrations between about 0.1-200 mM or more. Generally, the intracellular concentration of cytosolic acetyl-CoA is between about 3-150 mM, particularly between about 5-125 mM and more particularly between about 8-100 mM, including about 10 nMNI, 20 mM, 50 mM, 80 mM, or more. Intracellular concentrations between and above each of these exemplary ranges also can be achieved from the non-naturally occurring organisms provided herein. -183- [003631 In certain embodiments, wherein the non-naturally occurring eukaryotic organism comprises an acetyl-CoA pathway and a 1,3-3DO pathway, the organisms can be constructed using methods well known in the art as exemplified herein to exogenously express at least one nucleic acid encoding an acetyl-CoA pathway and/or 1,3-BDO pathway enzyme or protein in sufficient amounts to produce acetyl-CoA and/or 1,3-BDO. It is understood that the organisms provided herein can be cultured under conditions sufficient to produce cytosolic acetyl-CoA and/or 1,3-BD). Following the teachings and guidance provided herein, the non-naturally occurring organisms provided herein can achieve biosynthesis of 1,3-BDO resulting in intracellular concentrations between about 0.1-2000 mM or more. Generally, the intracellular concentration of 1,3-BDO is between about 3-1800 mM. particularly between about 5-1700 mM and more particularly between about 8-1600 mMI, including about 100 mM, 200 mM, 500 mM, 800 mM, or more. Intracellular concentrations between and above each of these exemplary ranges also can be achieved from the non-naturally occurring organisms provided herein. [003641 In some embodiments, culture conditions include anaerobic or substantially anaerobic growth or maintenance conditions. Exemplary anaerobic conditions have been described previously and are well known in the art. Exemplary anaerobic conditions for fermentation processes are described herein and are described, for example, in U.S. publication 2009/0047719, filed August 10, 2007. Any of these conditions can be employed with the non naturally occurring eukaryotic organisms as well as other anaerobic conditions well known in the art. Under such anaerobic or substantially anaerobic conditions, the cytosolic acetyl-CoA producers can synthesize cytosolic acetyl-CoA at intracellular concentrations of 0.005-1000 mM or more as well as all other concentrations exemplified herein. It is understood that, even though the above description refers to intracellular concentrations, cytosolic acetyl-CoA producing eukaryotic organisms can produce cytosolic acetvl-CoA intracellularly and/or secrete the product into the culture medium. In embodiments, wherein the non-naturally occurring eukaryotic organism further comprises a 1,3-BDO pathway, under such anaerobic conditions, the 1,3-BDO producers can synthesize 1,3-BDO at intracellular concentrations of 5-10 mM or more as well as all other concentrations exemplified herein. It is understood that, even though the above description refers to intracellular concentrations, 1,3-BDO producing eukaryotic organisms can produce 1,31-BDO intracellularly and/or secrete the product into the culture medium. -184- [003651 In addition to the culturing and fermentation conditions disclosed herein, growth condition for achieving biosynthesis of cytosolic acetyl-CoA and/or 1,3-3DO can include the addition of an osmoprotectant to the culturing conditions. In certain embodiments, the non naturally occurring eukaryotic organisms provided herein can be sustained, cultured or fenrmented as described herein in the presence of an osmoprotectant. Briefly, an osmoprotectant refers to a compound that acts as an osmolyte and helps a eukaryotic organism as described herein survive osmotic stress. Osmoprotectants include, but are not limited to, betaines, amino acids, and the sugar trehalose. Non-limiting examples of such are glycine betaine, praline betaine, dim ethylthetin, dimethyl sifonioproprionate, 3 -dimethylsulfornio-2-methylproprionate, pipecolic acid, dimethylsulfonioacetate, choline, L-camitine and ectoine. In one aspect, the osmoprotectant is glycine betaine. It is understood to one of ordinary skill in the art that the amount and type of osmoprotectant suitable for protecting a eukaryotic organism described herein from osmotic stress will depend on the eukaryotic organisrn used. The amount of osmoprotectant in the culturing conditions can be, for example, no more than about 0 1 mM, no more than about 0.5 mnM, no more than about 1.0 mM, no more than about 1.5 mM, no more than about 2.0 mM, no more than about 2.5 mM, no more than about 3.0 mM, no more than about 5.0 mM, no more than about 7.0 mM, no more than about 10 mM, no more than about 50 mM, no more than about 100 mM or no more than about 500 mM, 1003661 In some embodiments, the carbon feedstock and other cellular uptake sources such as phosphate, ammonia, sulfate, chloride and other halogens can be chosen to alter the isotopic distribution of the atoms present in cytosolic acetyl-CoA or any acetyl-CoA pathway intermediate. The various carbon feedstock and other uptake sources enumerated above will be referred to herein, collectively, as "uptake sources." Uptake sources can provide isotopic enrichment for any atom present in the product cytosolic acetyl-CoA or acetvl-CoA pathway intermediate including any cytosolic acetyl-CoA impurities generated in diverging away from the pathway at any point. Uptake sources can also provide isotopic enrichment for any atom present in the product 1,3-BDO or 1,3-BDO pathway intermediate including any 1,3-BDO impurities generated by diverging away from the pathway at any point. Isotopic enrichment can be achieved for any target atom including, for example, carbon, hydrogen, oxygen, nitrogen, sulfur, phosphorus, chloride or other halogens. -185- [003671 In some embodiments, the uptake sources can be selected to alter the carbon-12, carbon-13, and carbon-14 ratios. In some embodiments, the uptake sources can be selected to alter the oxygen-16, oxygen-17, and oxygen-18 ratios. In some embodiments, the uptake sources can be selected to alter the hydrogen, deuterium, and tritium ratios. In some embodiments, the uptake sources can be selected to alter the nitrogen-14 and nitrogen-15 ratios. In some embodiments, the uptake sources can be selected to alter the sulfur-32, sulfur-33, sulfur-34, and sulfur-35 ratios. In some embodiments, the uptake sources can be selected to alter the phosphorus-31, phosphorus-32, and phosphorus-33 ratios. In some embodiments, the uptake sources can be selected to alter the chlorine-35, chlorine-36, and chlorine-37 ratios. 1003681 In some embodiments, a target isotopic ratio of an uptake source can be obtained via synthetic chemical enrichment of the uptake source. Such isotopically enriched uptake sources can be purchased commercially or prepared in the laboratory. In some embodiments, a target isotopic ratio of an uptake source can be obtained by choice of origin of the uptake source in nature. In some embodiments, the isotopic ratio of a target atom can be varied to a desired ratio by selecting one or more uptake sources. An uptake source can be derived from a natural source, as found in nature, or from a man-made source. and one skilled in the art can select a natural source, a man-made source, or a combination thereof, to achieve a desired isotopic ratio of a target atom. An example of a man-made uptake source includes, for example, an uptake source that is at least partially derived from a chemical synthetic reaction. Such isotopically enriched uptake sources can be purchased commercially or prepared in the laboratory and/or optionally mixed with a natural source of the uptake source to achieve a desired isotopic ratio. In some embodiments, a target atom isotopic ratio of an uptake source can be achieved by selecting a desired origin of the uptake source as found in nature. For example, as discussed herein, a natural source can be a biobased derived from or synthesized by a biological organism or a source such as petroleum-based products or the atmosphere. In some such embodiments, a source of carbon, for example, can be selected from a fossil tuel-derived carbon source, which can be relatively depleted of carbon-14, or an environmental carbon source. such as C02, which can possess a larger amount of carbon- 14 than its petroleum-derived counterpart. -186- [003691 The unstable carbon isotope carbon-14 or radiocarbon makes up for roughly 1 in 1012 carbon atoms in the earth's atmosphere and has a half-life of about 5700 years. The stock of carbon is replenished in the upper atmosphere by a nuclear reaction involving cosmic rays and ordinary nitrogen (14N). Fossil fuels contain no carbon-14, as it decayed long ago. Burning of fossil fuels lowers the atmospheric carbon-14 fraction, the so-called "Suess effect". 1003701 Methods of determining the isotopic ratios of atoms in a compound are well known to those skilled in the art. Isotopic enrichment is readily assessed by mass spectrometry using techniques known in the art such as accelerated mass spectrometry (AMS), Stable Isotope Ratio Mass Spectrometry (SIRMS) and Site-Specific Natural Isotopic Fractionation by Nuclear Magnetic Resonance (SN!F-NMR). Such mass spectral techniques can be integrated with separation techniques such as liquid chromatography (LC), high performance liquid chromatography (HPLC) and/or gas chromatography, and the like. [003711 In the case of carbon, ASTM D6866 was developed in the United States as a standardized analytical method for determining the biobased content of solid, liquid, and gaseous samples using radiocarbon dating by the American Society for Testing and Materials (ASTM) International. The standard is based on the use of radiocarbon dating for the determination of a product's biobased content. ASTM D6866 was first published in 2004, and the current active version of the standard is ASTM 1)6866-11 (effective April 1, 2011). Radiocarbon dating techniques are well known to those skilled in the art, including those described herein. [003721 The biobased content of a compound is estimated by the ratio of carbon-14 (IC) to carbon-12 ("C). Specifically, the Fraction Modern (Fm) is computed from the expression: Fm= (S-B)/(M-B), where B, S and M represent the 1C/ZC ratios of the blank, the sample and the modern reference, respectively. Fraction Modern is a measurement of the deviation of the

C/'

2 C ratio of a sample from "Modern." Modern is defined as 95% of the radiocarbon concentration (in AD 1950) of National Bureau of Standards (NBS) Oxalic Acid I (i.e., standard reference materials (SRM) 4990b) normalized to 60 CyPDr=-19 per mil. Olsson, The use of Oxalic acid ais a Standard. in, Radiocarbon Variations and Absolute Chronology, Nobel Symposium, 12th Proc., John Wiley & Sons, New York (1970). Mass spectrometry results, for example, measured by ASM, are calculated using the internationally agreed upon definition of -187- 0.95 times the specific activity of NBS Oxalic Acid I (SRM 4990b) normalized to 6 1 3 Cypjs=-19 per mi . This is equivalent to an absolute (AD 1950) 'C/'C ratio of 1.176 + 0,010 x 10 (Karlen et al., Arkiv 6Ceofvsik, 4:465-471 (1968)). The standard calculations take into account the differential uptake of one isotope with respect to another, for example, the preferential uptake in biological systems of C 1 - over C over C 1 , and these corrections are reflected as a Fm corrected for 61. [003731 An oxalic acid standard (SRM 4990b or HOx 1) was made from a crop of 1955 sugar beet. Although there were 1000 lbs made, this oxalic acid standard is no longer commercially available. The Oxalic Acid II standard (HOx 2; N.I.S.T designation SRM 4990 C) was made from a crop of 1977 French beet molasses. In the early 1980's, a group of 12 laboratories measured the ratios of the two standards. The ratio of the activity of Oxalic acid II to I is 1.2933i0.001 (the weighted mean). The isotopic ratio of H Ox II is -17.8 per mille. ASTM D6866-11 suggests use of the available Oxalic Acid II standard SRM 4990 C (Hox2) for the modern standard (see discussion of original vs. currently available oxalic acid standards in Mann, Radiocarbon, 25(2):519-527 (1983)). A Fm = 0% represents the entire lack of carbon-14 atoms in a material, thus indicating a fossil (for example, petroleum based) carbon source. A Fm 100%, after correction for the post-1950 injection of carbon-14 into the atmosphere from nuclear bomb testing, indicates an entirely modern carbon source. As described herein, such a "modern" source includes biobased sources. [003741 As described in ASTM D6866, the percent modern carbon (pMC) can be greater than 100% because of the continuing but diminishing effects of the 1950s nuclear testing programs, which resulted in a considerable enrichment of carbon-14 in the atmosphere as described in ASTM D6866- 11. Because all sample carbon-14 activities are referenced to a "pre-bomb" standard, and because nearly all new biobased products are produced in a post-bomb environment, all pMC values (after correction for isotopic fraction) must be multiplied by 0.95 (as of 2010) to better reflect the true biobased content of the sample. A biobased content that is greater than 103% suggests that either an analytical error has occurred, or that the source of biobased carbon is more than several years old. -188- [003751 ASTM D6866 quantifies the biobased content relative to the material's total organic content and does not consider the inorganic carbon and other non-carbon containing substances present. For example, a product that is 50% starch-based material and 50% water would be considered to have a Biobased Content = 100% (50% organic content that is 100% biobased) based on ASTM D6866. In another example, a product that is 50% starch-based material, 25% petroleum-based, and 25% water would have a Biobased Content:= 66.7% (75% organic content but only 50% of the product is biobased). In another example, a product that is 50% organic carbon and is a petroleum-based product would be considered to have a Biobased Content = 0% (50% organic carbon but from fossil sources). Thus, based on the well known methods and known standards for determining the biobased content of a compound or material, one skilled in the art can readily determine the biobased content and/or prepared downstream products that utilize of the invention having a desired biobased content. [003761 Applications of carbon- 14 dating techniques to quantify bio-based content of materials are known in the art (Currie et al., Nuclear Instruments and Methods in Physics Research 8, 172:281-287 (2000)). For example, carbon-14 dating has been used to quantify bio-based content in terephthalate-containing materials (Colonna et al., Green Chemnistry, 13:2543-2548 (2011)). Notably, polypropylene terephthalate (PPT) polymers derived from renewable 1,3 propanediol and petroleum-derived terephthalic acid resulted in Fm values near 30% (i.e., since 3/11 of the polymeric carbon derives from renewable 1,3-propanediol and 8/11 from the fossil end member terephthalic acid) (Currie et aL, supra, 2000). In contrast, polybutylene terephthalate polymer derived from both renewable 1,4-butanediol and renewable terephthalic acid resulted in bio-based content exceeding 90% (Colonna et al., supra, 2011). [003771 Accordingly, in some embodiments, provided herein is a cytosolic acetyl-CoA or a cytosolic acetyl-CoA intermediate that has a carbon-12, carbon-13, and carbon-14 ratio that reflects an atmospheric carbon uptake source. For example, in some aspects the cytosolic acetyl CoA or cytosolic acetyl-CoA intermediate can have an Fm value of at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 651, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98% or as much as 100%. In some embodiments, the uptake -189source is C02. In some embodiments, the cytosolic acetyl-CoA or cytosolic acetyl-CoA intermediate has a carbon-12, carbon-13, and carbon-14 ratio that reflects petroleum-based carbon uptake source. In some embodiments, the cytosolic acetyl-CoA or cytosolic acetyl-CoA intermediate that has a carbon-12, carbon- 13, and carbon-14 ratio that is obtained by a combination of an atmospheric carbon uptake source with a petroleum-based uptake source. In this aspect, the cytosolic acetyl-CoA or cytosolic acetyl-CoA intermediate can have an Fm value of less than 95%, less than 90%, less than 85%, less than 80%, less than 75%, less than 70%, less than 65%, less than 60%, less than 55%, less than 50%, less than 45%, less than 40%, less than 35%, less than 30%, less than 25%, less than 20%, less than 15%, less than 10%, less than 5%, less than 2% or less than 1%. In some embodiments, provided herein is a cytosolic acetvl-CoA or cytosolic acetyl-CoA intermediate that has a carbon-12, carbon-13, and carbon-I 4 ratio that is obtained by a combination of an atmospheric carbon uptake source with a petroleum-based uptake source. Using such a combination of uptake sources is one way by which the carbon- 12, carbon-13, and carbon-14 ratio can be varied, and the respective ratios would reflect the proportions of the uptake sources. [003781 In other embodiments, wherein the eukaryotic organism further comprises a 1 ,3-BDO pathway, provided herein is a 1,3-13D0 or I,3-BDO intermediate that has a carbon-12, carbon 13, and carbon-14 ratio that reflects an atmospheric carbon uptake source. For example, in some aspects the 1,3-13DO or I,3-BDO intermediate can have an Fm value of at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98% or as much as 1 00%. In some embodiments, the uptake source is C02. In some embodiments, the 1,3-BDO or 1,3-BDO intermediate has a carbon-12, carbon-13, and carbon-14 ratio that reflects petroleum-based carbon uptake source. In some embodiments, the 1,3-BDO or 1,3-BDO intermediate has a carbon-12, carbon-13, and carbon-14 ratio that is obtained by a combination of an atmospheric carbon uptake source with a petroleum-based uptake source. In this aspect, the 1,3-BDO or 1,3-BDO intermediate can have an Fm value of less than 95%, less than 90%, less than 85%, less than 80%, less than 75%, less than 70%, less than 65%, less than 60%, less than 55%, less than 50%, less than 45%, less than 40%, less than 35%, less than 30%, less than 25%, less than 20%, less than 15%, less than 10%, -190less than 5%, less than 2% or less than 1%. In some embodiments, provided herein is a 1.3-BDO or I,3-BDO intermediate that has a carbon-12, carbon-I 3, and carbon-14 ratio that is obtained by a combination of an atmospheric carbon uptake source with a petroleum-based uptake source. Using such a combination of uptake sources is one way by which the carbon-12, carbon-13, and carbon-14 ratio can be varied, and the respective ratios would reflect the proportions of the uptake sources. [003791 Further, the present invention relates to the biologically produced 1,3-BDO or 1,3 BDO intermediate as disclosed herein, and to the products derived therefrom, wherein the 1,3 BDO or a 1,3-BDO intermediate has a carbon-12, carbon-13, and carbon-14 isotope ratio of about the same value as the CO 2 that occurs in the environment. For example, in some aspects the invention provides: bioderived 1,3-BDO or a bioderived l,3-BDO intermediate having a carbon-i2 versus carbon-1 3 versus carbon-i4 isotope ratio of about the same value as the CO2 that occurs in the environment, or any of the other ratios disclosed herein. It is understood, as disclosed herein, that a product can have a carbon-12 versus carbon-13 versus carbon-14 isotope ratio of about the same value as the CO 2 that occurs in the environment, or any of the ratios disclosed herein, wherein the product is generated from bioderived 1,3-BDO or a bioderived 1,3 BDO intermediate as disclosed herein, wherein the bioderived product is chemically modified to generate a final product. Methods of chemically modifying a bioderived product of 1,3-BDO. or an intermediate thereof, to generate a desired product are well known to those skilled in the art, as described herein. The invention further provides organic solvents, polyurethane resins, polyester resins, hypoglycaemic agents, butadiene and/or butadiene-based products having a carbon-12 versus carbon-13 versus carbon-14 isotope ratio of about the same value as the CO2 that occurs in the environment, wherein the organic solvents, polyurethane resins, polyester resins, hypoglycaemic agents, butadiene and/or butadiene-based products are generated directly from or in combination with bioderived 1 ,3-BDO or a bioderived I ,3-BDO intennediate as disclosed herein. [003801 1,3-13DO is a chemical commonly used in many commercial and industrial applications, and is also used as a raw material in the production of a wide range of products. Non-limiting examples of such applications and products include organic solvents, polyurethane -191resins, polyester resins, hypoglycaienic agents, butadiene and/or butadiene-based products organic solvents, polyure thane resins, polyester resins, hypoglycaemic agents, butadiene and/or butadiene-based products. Accordingly, in some embodiments, the invention provides biobased used as a raw material in the production of a wide range of products comprising one or more bioderived 1,3-BDO or bioderived 1,3-BDO intermediate produced by a non-naturally occurring microorganism of the invention or produced using a method disclosed herein. [003811 As used herein, the term "bioderived" means derived from or synthesized by a biological organism and can be considered a renewable resource since it can be generated by a biological organism. Such a biological organism, in particular the microbial organisms of the invention disclosed herein, can utilize feedstock or biomass, such as, sugars or carbohydrates obtained from an agricultural, plant, bacterial, or animal source. Alternatively, the biological organism can utilize atmospheric carbon. As used herein, the terni "biobased" means a product as described above that is composed, in whole or in part, of a bioderived compound of the invention. A biobased or bioderived product is in contrast to a petroleum derived product, wherein such a product is derived from or synthesized from petroleum or a petrochemical feedstock. [003821 In some embodiments, the invention provides organic solvents, polyurethane resins, polyester resins, hypoglycaemic agents, butadiene and/or butadiene-based products comprising bioderived 1,3-1BDO or bioderived 1,3-BDO intermediate, wherein the bioderived 1 ,3-BDO or bioderived I ,3-BDO intermediate includes all or part of the 1,3-BDO or I,3-BDO intermediate used in the production of organic solvents, polyurethane resins, polyester resins, hypoglycaemic agents, butadiene and/or butadiene-based products. Thus, in some aspects, the invention provides biobased organic solvents, polyurethane resins, polyester resins, hypoglycaemic agents, butadiene and/or butadiene-based products comprising at least 2%, at least 3%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98% or 100% bioderived 1,3-3DO or bioderived 1,3-3DO intermediate as disclosed herein. Additionally, in some aspects, the invention provides biobased organic solvents, polyurethane resins, polyester resins, hypoglycaeniic agents, butadiene and/or butadiene-based products -192wherein the 1,3-BDO or 1,3-BDO intermediate used in its production is a combination of bioderived and petroleum derived 1,3-BDO or 1,3-BDO intermediate. For example, biobased organic solvents, polyurethane resins, polyester resins, hypoglycaemic agents, butadiene and/or butadiene-based products can be produced using 50% bioderived 1,3-13DO and 50% petroleum derived 1,3-BDO or other desired ratios such as 60%/40%, 70%/30%, 80%/20%, 90%/10%, 95%/ 5%, 10%/0%, 40%/60%, 30%4/70%, 20%/80%, 1 0%/90% of bioderived/petroleum derived precursors, so long as at least a portion of the product comprises a bioderived product produced by the microbial organisms disclosed herein. It is understood that methods for producing organic solvents, polyurethane resins, polyester resins, hypoglycaemic agents, butadiene and/or butadiene-based products using the bioderived 1,3-BDO or bioderived 1,3-BDO intermediate of the invention are well known in the art. [00383] The culture conditions can include, for example, liquid culture procedures as well as fennentation and other large scale culture procedures. As described herein, particularly useful yields of cytosolic acetyl-CoA and/or biosynthetic products, such as 1,3-B DO and others, can be obtained under anaerobic or substantially anaerobic culture conditions. 1003841 As described herein, one exemplary growth condition for achieving biosynthesis of cytosolic acetyl-CoA and/or 1,3-BDO includes anaerobic culture or fermentation conditions. In certain embodiments, the non-naturally occurring eukaryotic organisms provided herein can be sustained, cultured or fermented under anaerobic or substantially anaerobic conditions. Briefly, anaerobic conditions refer to an environment devoid of oxygen. Substantially anaerobic conditions include, for example, a culture, batch fermentation or continuous fennentation such that the dissolved oxygen concentration in the medium remains between 0 and 10% of saturation. Substantially anaerobic conditions also includes growing or resting cells in liquid medium or on solid agar inside a sealed chamber maintained with an atmosphere of less than 1% oxygen. The percent of oxygen can be maintained by, for example, sparging the culture with an N2/CO 2 mixture or other suitable non-oxygen gas or gases. [003851 The culture conditions described herein can be scaled up and grown continuously for producing cytosolic acetyl-CoA. Exemplary growth procedures include, for example, fed-batch fermentation and batch separation; fed-batch fermentation and continuous separation, or -193continuous fermentation and continuous separation. All of these processes are well known in the art. Fermentation procedures are particularly useful for the biosynthetic production of cytosolic acetyl-CoA. Generally, and as with non-continuous culture procedures, the continuous and/or near-continuous production of cytosolic acetyl-CoA will include culturing a non-naturally occurring cytosolic acetyi-CoA producing organism provided herein further comprising a biosynthetic pathway for the production of a compound that can be synthesized using cytosolic acetyl-CoA in sufficient nutrients and medium to sustain and/or nearly sustain growth in an exponential phase. The culture conditions described herein can likewise be used, scaled up and grown continuously for manufacturing of 1,3-BDO. Fermentation procedures are particularly useful for the biosynthetic production of commercial quantities of 1.3-BDO. Generally, and as with non-continuous culture procedures, the continuous and/or near-continuous production of 1 ,3-BDO will include culturing a non-naturally occurring 1,3-BDO producing organism in sufficient nutrients and medium to sustain and/or nearly sustain growth in an exponential phase. [003861 Continuous culture under such conditions can include, for example, growth for I day, 2, 3, 4, 5, 6 or 7 days or more. Additionally, continuous culture can include longer time periods of I week, 2, 3, 4 or 5 or more weeks and up to several months. Alternatively, organisms provided herein can be cultured for hours, if suitable for a particular application. It is to be understood that the continuous and/or near-continuous culture conditions also can include all time intervals in between these exemplary periods. It is further understood that the time of culturing the eukaryotic organisms provided herein is for a sufficient period of time to produce a sufficient amount of product for a desired purpose. [00387] Fermentation procedures are we] I known in the art. Briefly, fermentation for the biosynthetic production of cytosolic acetyl-CoA can be utilized in, for example, fed-batch fermentation and batch separation; fed-batch fermentation and continuous separation, or continuous fermentation and continuous separation. Examples of batch and continuous fermentation procedures are well known in the art. [00388] In addition to the above fermentation procedures using the cytosolic acetyl-CoA producers provided herein for continuous production of substantial quantities of cvtosolic acetyl CoA, the cytosolic acetyl-CoA producers also can be, for example, simultaneously subjected to -194chemical synthesis procedures to convert the product to other compounds or the product can be separated from the fermentation culture and sequentially subjected to chemical or enzymatic conversion to convert the product to other compounds, if desired. Likewise, 1,3-BDO producers also can be, for example, simultaneously subjected to chemical synthesis procedures to convert the product to other compounds or the product can be separated from the fermentation culture and sequentially subjected to chemical conversion to convert the product to other compounds, if desired. For example, 1,3-13DO can be dehydrated to provide 1,343DO. In some embodiments, a non-naturally occurring eukaryotic organism comprising an acetyl-CoA pathway further comprises a biosynthetic pathway for the production of a compound that uses cytosolic acetyl CoA as a precursor, the biosynthetic pathway comprising at least one exogenous nucleic acid encoding an enzyme expressed in a sufficient amount to produce the compound. Compounds of interest that can be produced be produced using cytosolic acetyl-CoA as a precursor include 1,3 BDO and others. [003891 In some embodiments, syngas can be used as a carbon feedstock. Important process considerations for a syngas fermentation are high biomass concentration and good gas-liquid mass transfer (Bredwell et al., Biotechnol Prog., 15:834-844 (1999). The solubility of CO in water is somewhat less than that of oxygen. Continuously gas-sparged fermentations can be performed in controlled fermenters with constant off-gas analysis by mass spectrometry and periodic liquid sampling and analysis by CK and -PLC. The liquid phase can function in batch mode. Fermentation products such as alcohols, organic acids, and residual glucose along with residual methanol are quantified by HPLC (Shimadzu, Columbia MD), for example, using an Aminex' series of HPLC columns (for example, HPX-87 series) (BioRad, Hercules CA), using a refractive index detector for glucose and alcohols, and a UV detector for organic acids. The growth rate is determined by measuring optical density using a spectrophotometer (600 nm). All piping in these systems is glass or metal to maintain anaerobic conditions. The gas sparging is performed with glass fits to decrease bubble size and improve mass transfer. Various sparging rates are tested, ranging from about 0.1 to I vvm (vapor volumes per minute). To obtain accurate measurements of gas uptake rates, periodic challenges are performed in which the gas flow is temporarily stopped, and the gas phase composition is monitored as a function of time. -195- [003901 In order to achieve the overall target productivity, methods of cell retention or recycle are employed. One method to increase the microbial concentration is to recycle cells via a tangential flow membrane from a sidestream. Repeated batch culture can also be used, as previously described for production of acetate by Moorella (Sakai et al., J Biosci. Bioeng, 99:252-258 (2005)). Various other methods can also be used (Bredwell et aL, Biotechnol Prog., 15:834-844 (1999); Datar et aL, Biotechnol Bioeng, 86:587-594 (2004)). Additional optimization can be tested such as overpressure at 1.5 atm to improve mass transfer (Najafpour et aL, Enzyme and Microbial Technology, 38[1-2]. 223-228 (2006)). [003911 Once satisfactory performance is achieved using pure H2/CO as the feed, synthetic gas mixtures are generated containing inhibitors likely to be present in commercial syngas. For example. a typical impurity profile is 4.5% CH4, 0.1% C2H2, 0.35% C2H6, 1.4% C2H4, and 150 ppm nitric oxide (Datar et aL., Biotechnol Bioeng, 86:587-594 (2004)). Tars, represented by compounds such as benzene, toluene, ethylbenzene, p-xylene, o-xylene, and naphthalene, are added at ppm levels to test for any effect on production. For example, it has been shown that 40 ppm NO is inhibitory to C. carboxidivorans (Ahmed et al., Biotechnol Bioeng, 97:1080-1086 (2007)). Cultures are tested in shake-flask cultures before moving to a fermentor. Also, different levels of these potential inhibitory compounds are tested to quantify the effect they have on cell growth. This knowledge is used to develop specifications for syngas purity, which is utilized for scale up studies and production. If any particular component is found to be difficult to decrease or remove from syngas used for scale up, an adaptive evolution procedure is utilized to adapt cells to tolerate one or more impurities. [00392] Advances in the field of protein engineering make it feasible to alter any of the enzymes disclosed herein to act efficiently on substrates not known to be natural to them. Below are several examples of broad-specificity enzymes from diverse classes of interest and methods that have been used for evolving such enzymes to act on non-natural substrates. 1003931 To generate better producers, metabolic modeling can be utilized to optimize growth conditions. Modeling can also be used to design gene knockouts that additionally optimize utilization of the pathway (see, for example, U.S. patent publications US 2002/0012939, US 2003/0224363, US 2004/0029149, US 2004/0072723, US 2003/0059792, US 2002/0168654 and -196- US 2004/0009466, and U.S. Patent No. 7,127,379). Modeling analysis allows reliable predictions of the effects on cell growth of shifting the metabolism towards more efficient production of cytosolic acetyl-CoA. [003941 One computational method for identifying and designing metabolic alterations favoring biosynthesis of a desired product is the OptKnock computational framework (Burgard et al., Biotechnol. Bioeng. 84:647-657 (2003)). OptKnock is a metabolic modeling and simulation program that suggests gene deletion or disruption Methods that result in genetically stable eukaryotic organisms which overproduce the target product. Specifically, the framework examines the complete metabolic and/or biochemical network of a eukaryotic organism in order to suggest genetic manipulations that force the desired biochemical to become an obligatory byproduct of cell growth. By coupling biochemical production with cell growth through strategically placed gene deletions or other functional gene disruption, the growth selection pressures imposed on the engineered strains after long periods of time in a bioreactor lead to improvements in performance as a result of the compulsory growth-coupled biochemical production. Lastly, when gene deletions are constructed there is a negligible possibility of the designed strains reverting to their wild-type states because the genes selected by OptKnock are to be completely removed from the genorne. Therefore, this computational methodology can be used to either identify alternative pathways that lead to biosynthesis of a desired product or used in connection with the non-naturally occurring eukaryotic organisms for further optimization of biosynthesis of a desired product. 1003951 Briefly, OptKnock is a tern used herein to refer to a computational method and system for modeling cellular metabolism. The OptKnock program relates to a framework of models and methods that incorporate particular constraints into flux balance analysis (FBA) models. These constraints include, for example, qualitative kinetic information, qualitative regulatory information, and/or DNA microarray experimental data. OptKnock also computes solutions to various metabolic problems by, for example, tightening the flux boundaries derived through flux balance models and subsequently probing the performance limits of metabolic networks in the presence of gene additions or deletions. OptKnock computational framework allows the construction of model formulations that allow an effective query of the performance -197limits of metabolic networks and provides methods for solving the resulting mixed-integer linear programming problems. The metabolic modeling and simulation methods referred to herein as OptKnock are described in, for example, U.S. publication 2002/0168654, filed January 10, 2002, in International Patent No. PCT/US02/00660, filed January 10, 2002, and U.S. publication 2009/0047719, filed August 10, 2007. 1003961 Another computational method for identifying and designing metabolic alterations favoring biosynthetic production of a product is a metabolic modeling and simulation system termed SimPhenyni. This computational method and system is described in, for example, U.S. publication 2003/0233218, filed June 14, 2002, and in International Patent Application No. PCT/USO3/18838, filed June 13, 2003. SirnPheny@ is a computational system that can be used to produce a network model in silico and to simulate the flux of mass, energy or charge through the chemical reactions of a biological system to define a solution space that contains any and all possible ftinctionalities of the chemical reactions in the system, thereby determining a range of allowed activities for the biological system. This approach is referred to as constraints-based modeling because the solution space is defined by constraints such as the known stoichiometry of the included reactions as well as reaction thermodynamic and capacity constraints associated with maximum fluxes through reactions. The space defined by these constraints can be interrogated to determine the phenotypic capabilities and behavior of the biological system or of its biochemical components. [003971 These computational approaches are consistent with biological realities because biological systems are flexible and can reach the same result in many different ways. Biological systems are designed through evolutionary mechanisms that have been restricted by fundamental constraints that all living systems must face. Therefore, constraints-based modeling strategy embraces these general realities. Further, the ability to continuously impose further restrictions on a network model via the tightening of constraints results in a reduction in the size of the solution space, thereby enhancing the precision with which physiological performance or phenotype can be predicted. [00398] Given the teachings and guidance provided herein, those skilled in the art will be able to apply various computational frameworks for metabolic modeling and simulation to design and -198implement biosynthesis of a desired compound in host organisms. Such metabolic modeling and simulation methods include, for example, the computational systems exemplified above as SimiPheny@ and OptKnock. For illustration, some methods are described herein with reference to the OptKnock computation framework for rnodeling and simulation. Those skilled in the art will know how to apply the identification, design and implementation of the metabolic alterations using OptKnock to any of such other metabolic modeling and simulation computational frameworks and methods well known in the art, [003991 The methods described above will provide one set of metabolic reactions to disrupt. Elimination of each reaction within the set or metabolic modification can result in a desired product as an obligatory product during the growth phase of the organism. Because the reactions are known, a solution to the bilevel OptKnock problem also will provide the associated gene or genes encoding one or more enzynes that catalyze each reaction within the set of reactions. Identification of a set of reactions and their corresponding genes encoding the enzymes participating in each reaction is generally an automated process, accomplished through correlation of the reactions with a reaction database having a relationship between enzymes and encoding genes. [004001 Once identified, the set of reactions that are to be disrupted in order to achieve production of a desired product are implemented in the target cell or organism by functional disruption of at least one gene encoding each metabolic reaction within the set. One particularly useful means to achieve functional disruption of the reaction set is by deletion of each encoding gene. However, in some instances, it can be beneficial to disrupt the reaction by other genetic aberrations including, for example, mutation, deletion of regulatory regions such as promoters or cis binding sites for regulatory factors, or by truncation of the coding sequence at any of a number of locations. These latter aberrations, resulting in less than total deletion of the gene set can be useful, for example, when rapid assessments of the coupling of a product are desired or when genetic reversion is less likely to occur. [004011 To identify additional productive solutions to the above described bilevel OptKnock problem which lead to further sets of reactions to disrupt or metabolic modifications that can result in the biosynthesis, including growth-coupled biosynthesis of a desired product, an -199optimization method, termed integer cuts, can be implemented. This method proceeds by iteratively solving the OptKnock problem exemplified above with the incorporation of an additional constraint referred to as an integer cut at each iteration. Integer cut constraints effectively prevent the solution procedure from choosing the exact same set of reactions identified in any previous iteration that obligatorily couples product biosynthesis to growth. For example, if a previously identified growth-coupled metabolic modification specifies reactions 1, 2, and 3 for disruption, then the following constraint prevents the same reactions from being simultaneously considered in subsequent solutions. The integer cut method is well known in the art and can be found described in, for example, Burgard et al., Siotechnol. Prog. 17:791-797 (2001). As with all methods described herein with reference to their use in combination with the Optlinock computational framework for metabolic modeling and simulation, the integer cut method of reducing redundancy in iterative computational analysis also can be applied with other computational frameworks well known in the art including, for example, SimPheny®. [004021 The methods exemplified herein allow the construction of cells and organisms that biosynthetically produce a desired product, including the obligatory coupling of production of a target biochemical product to growth of the cell or organism engineered to harbor the identified genetic alterations. Therefore, the computational methods described herein allow the identification and implementation of metabolic modifications that are identified by an in silicon method selected from OptKnock or SimPheny@. The set of metabolic modifications can include, for example, addition of one or more biosynthetic pathway enzymes and/or functional disruption of one or more metabolic reactions including, for example, disruption by gene deletion. [004031 As discussed above, the OptKnock methodology was developed on the premise that mutant microbial networks can be evolved towards their computationally predicted maximum growth phenotypes when subjected to long periods of growth selection. In other words, the approach leverages an organism's ability to self-optimize under selective pressures. The OptKnock framework allows for the exhaustive enumeration of gene deletion combinations that force a coupling between biochemical production and cell growth based on network stoichiometry. The identification of optimal gene/reaction knockouts requires the solution of a -200bilevel optimization problem that chooses the set of active reactions such that an optimal growth solution for the resulting network overproduces the biochemical of interest (Burgard et al., Biotechnol. Bioeng. 84:647-657 (2003)). [004041 An in silico stoichiometric model of . coli metabolism can be employed to identify essential genes for metabolic pathways as exemplified previously and described in, for example, U.S. patent publications US 2002/0012939, US 2003/0224363, US 2004/0029149, US 2004/0072723., US 2003/0059792, US 2002/0168654 and US 2004/0009466, and in U.S. Patent No. 7,127,379. As disclosed herein, the OptKnock mathematical framework can be applied to pinpoint gene deletions leading to the growth-coupled production of a desired product. Further, the solution of the bilevel OptKnock problem provides only one set of deletions. To enumerate all meaningful solutions, that is, all sets of knockouts leading to growth-coupled production formation, an optimization technique, terrned integer cuts, can be implemented. This entails iteratively solving the OptKnock problem with the incorporation of an additional constraint referred to as an integer cut at each iteration, as discussed above. [004051 As disclosed herein, a nucleic acid encoding a desired activity of anl acetyl-CoA pathway and/or I,3-BDO pathway can be introduced into a host organism. In some cases, it can be desirable to modify an activity of an acetyl-CoA pathway enzyme or protein and/or 1,3-BDO pathway enzyme or protein to increase production of cytosolic acetyl-CoA or 1,3-3DO, respectively. For example, known mutations that increase the activity of a protein or enzyme can be introduced into an encoding nucleic acid molecule. Additionally, optimization methods can be applied to increase the activity of an enzyme or protein and/or decrease an inhibitory activity, for example, decrease the activity of a negative regulator. [00406] One such optimization method is directed evolution. Directed evolution methods have made possible the modifi cation of an enzyme to function on an array of unnatural substrates. The substrate specificity of the lipase in P. aeruginosa was broadened by randomization of amino acid residues near the active site. This allowed for the acceptance of alpha-substituted carboxylic acid esters by this enzyme Reetz et al., Angew. Chem. Int. Ed Engl. 44:4192-4196 (2005)). In another successful attempt, DNA shuffling was employed to create an Escherichia coli aminotransferase that accepted n-branched substrates, which were -201poorly accepted by the wild-type enzyme (Yano et aL., Proc. Vat. Ac ad. Sci. U. S. A. 95:5511 5515 (1998)). Specifically, at the end of four rounds of shuffling, the activity of aspartate aminotransferase for valine and 2-oxovaline increased by up to five orders of magnitude, while decreasing the activity towards the natural substrate, aspartate, by up to 30-fold. Recently, an algorithm was used to design a retro-aldolase that could be used to catalyze the carbon-carbon bond cleavage in a non-natural and non-biological substrate, 4-hydroxy-4-(6-methoxy-2 naphthyl)-2-butanone. These algorithms used different combinations of four different catalytic motifs to design new enzymes and 20 of the selected designs for experimental characterization had four-fold improved rates over the uncatalyzed reaction (Jiang et al., Science 319:1387-1391 (2008)). Thus, not only are these engineering approaches capable of expanding the array of substrates on which an enzyme can act, but allow the design and construction of very efficient enzymes. For example, a method of DNA shuffling (random chimeragenesis on transient templates or RACHITT) was reported to lead to an engineered monooxygenase that had an improved rate of desulfurization on complex substrates as well as 20-fold faster conversion of a non-natural substrate ( Coco et al, Nat. Biotechnol. 19:354-359 (2001)). Similarly, the specific activity of a sluggish mutant triosephosphate isomerase enzyme was improved up to 19-fold from 1.3 fold ( Hermes et al., Proc. NatL. Acad. Sci. U. S. A. 87:696-700 (1990)). This enhancement in specific activity was accomplished by using random mutagenesis over the whole length of the protein and the improvement could be traced back to mutations in six amino acid residues. [00407] The effectiveness of protein engineering approaches to alter the substrate specificity of an enzyme for a desired substrate has also been demonstrated. Isopropylmalate dehydrogenase from Thernws thermophilus was modified by changing residues close to the active site so that it could now act on malate and D-lactate as substrates (Fujita et al,, Biosci, Biotechnol Biochem. 65:2695-2700 (2001)). In this study as well as in others, it was pointed out that one or a few residues could be modified to alter the substrate specificity. A case in point is the dihydroflavonol 4-reductase for which a single amino acid was changed in the presumed substrate-binding region that could preferentially reduce dihydrokaempferol Johnson et al., PlantJ. 25:325-333 (2001)). 'The substrate specificity of a very specific isocitrate dehydrogenase from Escherichia coli was changed fironi isocitrate to isopropynialate by -202changing one residue in the active site ( Doyle et al., Biochemistry 40:234-4241 (2001)). In a similar vein, the cofactor specificity of a NAD--dependent 1,5-hydroxyprostaglandin dehydrogenase was altered to NADP+ by changing a few residues near the N-terminal end Cho et al., A rch. Biochem. Biophys. 419:139-146 (2003)). Sequence analysis and molecular modeling analysis were used to identify the key residues for modification, which were further studied by site-directed mutagenesis. [004081 A fucosidase was evolved from a galactosidase in E. coli by DNA shuffling and screening ( Zhang et al., Proc Natl Acad Sci US. A. 94:4504-4509 (1997)). Similarly, aspartate aminotransferase from E. coli was converted into a tyrosine aminotransferase using homology modeling and site-directed mutagenesis ( Onuffer et al., Protein Sci. 4:1750-1757 (1995)). Site directed mutagenesis of two residues in the active site of benzoyiformate decarboxylase from P. putida reportedly altered the affinity (Km) towards natural and non-natural substrates Siegert et al., Protein Eng Des Sel 18:345-357 (2005)). Cytochrome c peroxidase (CCP) from Saccharomvces cerevisiae was subjected to directed molecular evolution to generate mutants with increased activity against the classical peroxidase substrate guaiacol, thus changing the substrate specificity of CCP from the protein cytochrome c to a small organic molecule. After three rounds of DNA shuffling and screening, mutants were isolated which possessed a 300-fold increased activity against guaiacol and up to 1000-fold increased specificity for this substrate relative to that for the natural substrate ( Iffland et al., Biochemiswt 39:10790-10798 (2000)). [004091 In some cases, enzymes with different substrate preferences than both the parent enzymes have been obtained. For example, biphenyl-dioxygenase-mediated degradation of polychlorinated biphenyls was improved by shuffling genes from two bacteria, Pseudomonas pseudoalcaligens and Burkholderia cepacia (Kumamaru et al., Nat. Biotechno!. 16, 663-666 (1998)). The resulting chimeric biphenyl oxygenases showed different substrate preferences than both the parental enzymes and enhanced the degradation activity towards related biphenyl compounds and single aromatic ring hydrocarbons such as toluene and benzene which were originally poor substrates for the enzyme. [004101 It is not only possible to change the enzyme specificity but also to enhance the activities on those substrates on which the enzymes naturally have low activities. One study -203demonstrated that amino acid racemase from P. putida that had broad substrate specificity (on lysine, arginine, alanine, serine, methionine, cysteine, leucine and histidine among others) but low activity towards tryptophan could be improved significantly by random mutagenesis Kino et al., Appl. icrobiol. Biotechnol. 73:1299-1305 (2007)). Similarly, the active site of the bovine BCKAD was engineered to favor alternate substrate acetyl-CoA (Meng et al., Biochenistry 33:12879-12885 (1994)). An interesting aspect of these approaches is that even when random methods have been applied to generate these mutated enzymes with efficacious activities, the exact mutations or structural changes that confer the improvement in activity can be identified. For example, in the aforementioned study, the mutations that facilitated improved activity on tryptophan could be traced back to two different positions. [004111 Directed evolution has also been used to express proteins that are difficult to express. For example, by subjecting the horseradish peroxidase to rando inmutagenesis and gene recombination, mutants could be extracted that had more than 14-fold activity than the wild type (Lin et al., Biotechnol. Prog. 15:467-471 (1999)). [004121 A final example of directed evolution shows the extensive modifications to which an enzyme can be subjected to achieve a range of desired functions. The enzyme, lactate dehydrogenase from Bacillus stearothernophilus was subjected to site-directed mutagenesis, and three amino acid substitutions were made at sites that were indicated to determine the specificity towards different hydroxyacids (Clarke et al., Biochen. Biophys. Res. Conniun. 148:15-23 (1987)). After these mutations, the specificity for oxaloacetate over pyruvate was increased to 500 in contrast to the wild type enzyme that had a catalytic specificity for pyruvate over oxaloacetate of 1000. This enzyme was further engineered using site-directed mutagenesis to have activity towards branched-chain substituted pyruvates ( Wilks et al., Biochemistry 29:8587 8591 (1990)). Specifically, the enzyme had a 55-fold improvement in Kcat for alpha ketoisocaproate. Three structural modifications were made in the same enzyme to change its substrate specificity from lactate to malate. The enzyme was highly active and specific towards palate (Wilks et al., Science 242:1541-1544 (1988)), The same enzyme from B. stearothermophilus was subsequently engineered to have high catalytic activity towards alpha keto acids with positively charged side chains, such as those containing ammonium groups -204- (Hogan et al, Biochemistry 34:4225-4230 (1995)). Mutants with acidic amino acids introduced at position 102 of the enzyme favored binding of such side chain ammonium groups. The results obtained proved that the mutants showed up to 25-fold improvements in kcat/Km values for omega-amino-alpha-keto acid substrates. This enzyme was also structurally modified to function as a phenyllactate dehydrogenase instead of a lactate dehydrogenase (Wilks et al., Biochenistry 31:7802-7806 (1992)). Restriction sites were introduced into the gene for the enzyme which allowed a region of the gene to be excised. This region coded for a mobile surface loop of polypeptide (residues 98-110) which normally seals the active site vacuole from bulk solvent and is a major determinant of substrate specificity. The variable length and sequence loops were inserted into the cut gene and used to synthesize hydroxyacid dehydrogenases with altered substrate specificities. With one longer loop construction, activity with pyruvate was reduced one-million-fold but activity with phenylpyruvate was largely unaltered. A switch in specificity (kcat/Kn) of 390,000-fold was achieved. The 1700:1 selectivity of this enzyme for phenylpyruvate over pyruvate is that required in a phenyllactate dehydrogenase. 1004131 As indicated above, directed evolution is a powerful approach that involves the introduction of mutations targeted to a specific gene in order to improve and/or alter the properties of an enzyme. Improved and/or altered enzymes can be identified through the development and implementation of sensitive high-throughput screening assays that allow the automted anant p -e >104). I-erative rounds of automated screening of many enzyme variants (for example, > I r d mutagenesis and screening typically are performed to afford an enzyme with optimized properties. Computational algorithms that can help to identify areas of the gene for mutagenesis also have been developed and can significantly reduce the number of enzyme variants that need to be generated and screened. [004141 Numerous directed evolution technologies have been developed (for reviews, see Hibbert et al., Biomol, Eng 22:11-19 (2005); [Huisman and Lalonde, Biocatalysis in the Pharmaceutical and Biotechnology Industries pgs. 717-742 (2007), Patel (ed.), CRC Press; Otten and Quax. Biomol. Eng 22:1-9 (2005).; and Sen et al., AppIl Biochem. Biotechnol 143:212 23 (200 7 )) to be effective at creating diverse variant libraries, and these methods have been -205successfully applied to the improvement of a wide range of properties across many enzyme classes. [00415] Enzyme characteristics that have been improved and/or altered by directed evolution technologies include, for example: selectivity/specificity, for conversion of non-natural substrates: temperature stability, for robust high temperature processing: pH stability, for bioprocessing under lower or higher pH conditions; substrate or product tolerance, so that high product titers can be achieved; binding (Km,), including broadening substrate binding to include non-natural substrates; inhibition (Ki), to remove inhibition by products, substrates, or key intermediates; activity (kcat), to increases enzymatic reaction rates to achieve desired flux; expression levels, to increase protein yields and overall pathway flux: oxygen stability, for operation of air sensitive enzymes under aerobic conditions: and anaerobic activity, for operation of an aerobic enzyme in the absence of oxygen. [00416] A number of exemplary methods have been developed for the mnutagenesis and diversification of genes to target desired properties of specific enzymes. Such methods are well known to those skilled in the art Any of these can be used to alter and/or optimize the activity of an acetyl-CoA pathway enzyme or protein. Such methods include, but are not limited to EpPCR, which introduces random point mutations by reducing the fidelity of DNA polymerase in PCR reactions (Pritchard et aL, J Theor Biol. 234:497-509 (2005)); Error-prone Rolling Circle Amplification (epRCA), which is similar to epPCR except a whole circular plasmid is used as the template and random 6-mers with exonuclease resistant thiophosphate linkages on the last 2 nucleotides are used to amplify the plasmid followed by transformation into cells in which the plasmid is re-circularized at tandem repeats (Fujii et a]., Nucleic Acids Res. 32:e 145 (2004); and Fuiii et al., Nat. Protoc. 1:2493-2497 (2006)): DNA or Family Shuffling, which typically involves digestion of two or more variant genes with nucleases such as Dnase I or EndoV to generate a pool of random fragments that are reassembled by cycles of annealing and extension in the presence of DNA polymerase to create a library of chimeric genes (Stemmer, Proc Natl Acad Sci USA 91:10747-10751 (1994); and Stemmer, Nature 370:389-391 (1994)); Staggered Extension (StEP), which entails template priming followed by repeated cycles of 2 step PCR with denaturation and very short duration of annealing/extension (as short as 5 sec) (Zhao et aL , -206- Nat. Biotechnol. 16:258-261 (1998)); Random Priming Recombination (RPR), in which random sequence primers are used to generate many short DNA fragments complementary to different segments of the template (Shao et al., Nucleic Acids Res 26:681-683 (1998)). [004171 Additional methods include heteroduplex recombination, in which linearized plasmid DNA is used to form heteroduplexes that are repaired by mismatch repair (Volkov et al., Nucleic Acids Res. 27:e18 (1999); and Volkov et al., Methods Enzvmol. 328:456-463 (2000)); Random Chimeragenesis on Transient Templates (RACHITT), which employs Dnase I fragmentation and size fractionation of single stranded DNA (ssDNA) (Coco et al., Nat. Biotechnol, 19:354-359 (2001)); Recombined Extension on Truncated templates (RETT), which entails template switching of unidirectionally growing strands from primers in the presence of unidirectional ssDNA fragments used as a pool of templates (Lee et al., ,J. Molec. Catalysis 26:119-129 (2003)); Degenerate Oligonucleotide Gene Shuffling (DOGS), in which degenerate primers are used to control recombination between molecules; (Bergquist and Gibbs., Methods Aol. Biol 352:191-204 (2007); Bergquist et al., Biomol. Eng 22:63-72 (2005); Gibbs et al., Gene 271:13-20 (2001)); Incremental Truncation for the Creation of Hybrid Enzymes (ITCHY), which creates a combinatorial library with I base pair deletions of a gene or gene fragment of interest (Ostermeier et aL, Proc. Nat. Acad. Sci. USA 96:3562-3567 (1999); and Ostermeier et al., Nat, Biotechnol. 17:1205-1209 (1999)); Thio-Incremental Truncation for the Creation of Hybrid Enzymes (THIO-ITCHY) which is similar to ITCHY except that phosphothioate dNTPs are used to generate truncations (Lutz et al., Nucleic Acids Res 29:E 16 (2001 )); SCRATCHY, which combines two methods for recombining genes, ITCHY and DNA shuffling (Lutz et al., Proc. Natl. Acad. Sci. USA 98:11248-11253 (200 1)); Random Drift Mutagenesis (RNDM), in which mutations made via epPCR are followed by screening/selection for those retaining usable activity (Bergquist et al, Biomol. Eng. 22:63-72 (2005)); Sequence Saturation Mutagenesis (SeSaM), a random mutagenesis method that generates a pool of random length fragments using random incorporation of a phosphothioate nucleotide and cleavage, which is used as a template to extend in the presence of "universal" bases such as inosine, and replication of an inosine-containing complement gives random base incorporation and, consequently, mutagenesis (Wong et al., Biotechnol. J. 3:74-82 (2008); Wong et al., Nucleic Acids Res. 32:e26 (2004); and Wong et al., Anal. Biochein. 341:187-189 (2005)); Synthetic Shuffling, which uses overlapping -207oligonucleotides designed to encode "all genetic diversity in targets" and allows a very high diversity for the shuffled progeny (Ness et aL, Nat. Biotechnol. 20:1251-1255 (2002)); Nucleotide Exchange and Excision Technology NexT, which exploits a combination of dUTP incorporation followed by treatment with uracil DNA glycosylase and then piperidine to perform endpoint DNA fragmentation (Muller et al., Nucieic Acids Res. 33:el 17 (2005)). 1004181 Further methods include Sequence Homology-Independent Protein Recombination (SHIPREC), in which a linker is used to facilitate fusion between two distantly related or unrelated genes, and a range of chimeras is generated between the two genes, resulting in libraries of single-crossover hybrids (Sieber et al., Nat. BiotechnoL 19:456-460 (2001)); Gene Site Saturation MutagenesisTM (GSSMTrM), in which the starting materials include a supercoiled double stranded DNA (dsDNA) plasmid containing an insert and two primers which are degenerate at the desired site of mutations (Kretz et al., Methods Enzymol. 388:3-11 (2004)); Combinatorial Cassette Mutagenesis (CCM), which involves the use of short oligonucleotide cassettes to replace limited regions with a large number of possible amino acid sequence alterations (Reidhaar-Olson et al. Methods Enz7mol. 208:564-586 (1991); and Reidhaar-Olson et al. Science 241:53-57 (1988)); Combinatorial Multiple Cassette Mutagenesis (CMCM), which is essentially similar to CCM and uses epPCR at high mutation rate to identify hot spots and hot regions and then extension by CMCM to cover a defined region of protein sequence space (Reetz et al,, Angew. Chen. Int. Ed Engl. 40:3589-3591 (2001)); the Mutator Strains technique, in which conditional ts mutator plasmids, utilizing the nutD5 gene, which encodes a mutant subunit of DNA polymerase 1Il, to allow increases of 20 to 4000-X in random and natural mutation frequency during selection and block accumulation of deleterious mutations when selection is not required (Selifonova et al., Appl. Environ. Microbiol. 67:3645-3649 (2001)); Low et al., J. Mol. Biol. 260:359-3680 (1996)). 1004191 Additional exemplary methods include Look-Through Mutagenesis (LTM), which is a multidimensional mutagenesis method that assesses and optimizes combinatorial mutations of selected amino acids (Rajpal et at, Proc. atl. Acad. Sci. USA 102:8466-8471 (2005)); Gene Reassembly, which is a DNA shuffling method that can be applied to multiple genes at one time or to create a large library of chimeras (multiple mutations) of a single gene (Tunable -208- GeneReassemblyTM (TGRTM) Technology supplied by Verenium Corporation), in Silico Protein Design Automation (PDA), which is an optimization algorithm that anchors the structurally defined protein backbone possessing a particular fold, and searches sequence space for amino acid substitutions that can stabilize the fold and overall protein energetics, and generally works most effectively on proteins with known three-dimensional structures (Hayes et al., Proc. NIt. A cad. Sci. USA 99:15926-15931 (2002)); and Iterative Saturation Mutagenesis (ISM), which involves using knowledge of structure/function to choose a likely site for enzyme improvement, performing saturation mutagenesis at chosen site using a mutagenesis method such as Stratagene QuikChange (Stratagene; San Diego CA), screening/selecting for desired properties, and, using improved clone(s), starting over at another site and continue repeating until a desired activity is achieved (Reetz et al., Nat. Protoc. 2:891-903 (2007); and Reetz et al., Angew. Chem. Int. Ed Engl. 45:7745-7751 (2006)). [004201 Any of the aforementioned methods for mutagenesis can be used alone or in any combination. Additionally, any one or combination of the directed evolution methods can be used in conjunction with adaptive evolution techniques, as described herein. 1004211 It is understood that modifications which do not substantially affect the activity of the various embodiments provided herein are also provided within the definition provided herein. Accordingly, the following examples are intended to illustrate but not limit. EXAMPLE I PATHWAYS FOR PRODUCING CYTOSOLIC ACETYL-COA FROM MITOCHONDRIAL ACETYL-COA [004221 The production of cytosolic acetyl-CoA from mitochondrial acetyl-CoA can be accomplished by a number of pathways, for example, in three to five enzymatic steps. In one exemplary pathway, mitochondrial acetyl-CoA and oxaloacetate are combined into citrate by a citrate synthase and the citrate is exported out of the mitochondrion by a citrate or citrate/oxaloacetate transporter. Enzymatic conversion of the citrate in the cytosol results in cytosolic acetyl-CoA and oxaloacetate. The cytosolic oxaloacetate can then optionally be transported back into the mitochondrion by an oxaloacetate transporter and/or a citrate/oxaloacetate transporter. In another exemplary pathway, the cytosolic oxaloacetate is first -209enzymatically converted into malate in the cytosol and then optionally transferred into the mitochondrion by a palate transporter and/or a malate/citrate transporter. Mitochondrial malate can then be converted into oxaloacetate with a mitochondrial malate dehydrogenase. [004231 In yet another exemplary pathway, mitochondrial acetyl-CoA can be converted to cytosolic acetyl-CoA via a citramalate intermediate. For example, mitochondrial acetyl-CoA and pyruvate are converted to citramalate by citramalate synthase. Citramalate can then be transported into the cytosol by a citramalate or dicarboxylic acid transporter. Cytosolic acetyl CoA and pyruvate are then regenerated from citramalate, directly or indirectly, and the pyruvate can re-enter the mitochondria. [004241 Along these lines, several exemplary acetyl-CoA pathways for the production of cytosolic acetyl-CoA from mitochondrial acetyl-CoA are shown in FIGS. 2, 3 and 8. In one embodiment, mitochondrial oxaloacetate is combined with mitochondrial acetyl-CoA to form citrate by a citrate synthase (FIGS. 2, 3 and 8, A). The citrate is transported outside of the mitochondrion by a citrate transporter (FIGS. 2, 3 and 8, B), a citrate/oxaloacetate transporter (FIG. 2C) or a citrate/malate transporter (FIG, 3C). Cytosolic citrate is converted into cytosolic acetyl-CoA and oxaloacetate by an ATP citrate [yase (FIGS. 2, 3, D). In another pathway, cvtosolic citrate is converted into acetate and oxaloacetate by a citrate lyase (FIGS. 2 and 3, E). Acetate can then be converted into cytosolic acetyl-CoA by an acetyl-CoA synthetase or transferase (FIGS. 2 and 3. F). Alternatively, acetate can be converted by an acetate kinase (FIGS. 2 and 3, K) to acetyl phosphate, and the acetyl phosphate can be converted to cytosolic acetyl-CoA by a phosphotransacetylase (FIGS. 2 and 3, L). Exemplary enzyme candidates for acetyl-Co-A pathway enzymes are described below. [00425] The conversion of oxaloacetate and mitochondrial acetyl-CoA is catalyzed by a citrate synthase (FIGS. 2, 3 and 8, A). In certain embodiments, the citrate synthase is expressed in a mitochondrion of a non-naturally occurring eukaryotic organism provided herein. -210- TABLE 11 Protein GenBank ID G1 number Organism CIT I NP 014398.1 6324328 Sacaromvces cerevisiae S288c CIT2 NP 009931.1 6319850 Saccharonyces cervmisiae S288c GYP 3 NP-01 5325.1 6325257 S5accJharonvc'e cerei .si e S288c YALI0E02684p XP 503469.1 50551989 Yarrowia lipolytica YALIOE00638p XP 503380.1 50551811 Yarowia lipolytica ANT_1 876084 XP 001393983.1 145242820 Aspe.gilus niger CBS 513.88 ANT_1 1474074 XP 001393195.2 317030721 4spergillus niger CBS 513.88 AN_ 1 2950014 XP 001389414.2 317026339 Aspergil ls niger CBS 513.88 ANt 1 1226134 XP 00139673L1 145250435 Aspergillus niger CBS 513.88 gltA NP 415248.1 16128695 Ecleriuchia coli K-12 MG1655 [00426] Transport of citrate from the mitochondrion to the cytosol can be carried out by several transport proteins. Such proteins either export citrate directly (i.e., citrate transporter, FIGS. 2, 3 and 8, B) to the cytosol or export citrate to the cytosol while simultaneously transporting a molecule such as rnalate (i.e., citrate/malate transporter, FiG. 3C) or oxaloacetate (i.e., citrate/oxaloacetate transporter FIG. 2C) from the cytosol into the mitochondrion as shown in FIGS. 2, 3 and 8. Exemplary transport enzymes that carry out these transformations are provided in the table below. TABLE 12 Pro tein| GenBank ID GI number Organism CTP1 NP 0098501 6319768 Saccharonvces cerevisiae S288c YALI0F26323p XP 505902.1 50556988 Yarrowia lipot/ica ATEG 09970 EAU29419.1 114187719 Aspergillus terreus NIH2624 Kuveronvces lactis NRRL Y KLLA0E18723g XP 454797.1 50309571 1140 CTRG 02320 XP 002548023.1 255726194 Candida t;opical/s MYA-3404 -211- ANI 1 1474094 XP 0013950801 145245625 Aspergillus niger CBS 513.88 YH M2 NP 013968.1 6323897 Saccharomyces cerevisiae S288c DTC CAC 845491 19913113 Arabidopsis thaliana DTCI CAC84545 1 19913105 Nicotiana tabacun DTC2 CAC 845461 19913107 Nicotiana tabacum DTC3 CAC84547 1 19913109 Nicotiana tabacun DTC4 CAC84548.1 19913111 Nicotiana tabacua DTC AAR06239.1 37964368 Citrus junos [004271 ATP citrate lVase (ACL. EC 2.3.3.8, FIGS. 2 and 3. D), also called ATP citrate synthase, catalyzes the ATP-dependent cleavage of citrate to oxaloacetate and acetyl-CoA. In certain embodiments, ATP citrate lyase is expressed in the cytosol of a eukaryotic organism. ACL is an enzyme of the RTCA cycle that has been studied in green sulfur bacteria Chlorobiun imicola and Chlorobiumn tepidun. The alpha(4)beta(4) heteromeric enzyme from Chlorobiumn linicola was cloned and characterized in E. coli (Kanao et al., Ear. J. Biocheni. 269:3409-3416 (2002). The C. linmicola enzyme, encoded by aclAB, is irreversible and activity of the enzyme is regulated by the ratio of ADP/ATP. The Chlorobium tepid uni a recombinant ACL from Chlorobium tepidum was also expressed in E. coli and the holoenzyme was reconstituted in vitro, in a study elucidating the role of the alpha and beta subunits in the catalytic mechanism (Kim and Tabita, J Bacteriol. 188:6544-6552 (2006). ACL enzymes have also been identified in Balnearium lithotrophicum, Sulfurihydrogenibium subterraneum and other members of the bacterial phylurn Aquificae (Hugler em al., Environ. Microbiol. 9:81-92 (2007)). This activity has been reported in some fungi as well. Exemplary organisms include Sordaria nacrospora (Nowrousian et al., Curr. Genet. 37:189-93 (2000)), Aspergillus nidulans and Yarrowia lipolytica (Hynes and Murray, Eukarvotic Cell, July: 1039-1048, (2010) , and Aspergillus niger (Meijer etal. J Ind. MicrobioL Biotechnol. 36:1275-1280 (2009). Other candidates can be found based on sequence homology. Information related to these enzymes is tabulated below. -212- TABLE 13 Protein GenBank ID GI Number Organism acA BAB21376.1 12407237 Chlorobium linicola ac/B BAB21375.1 12407235 Chlorobiun /inicola ac/A AAM7232 1.1 21647054 Chlorobiun tepidun ac/B AAM7322 .1 21647055 Chlorobiun tepidum ac/B AB1-50084.1 114055039 Sidjithiydrogenibitii subterrancuin acL4 AAX76834.1 62199504 Sulfiurinonas denitrifcans ac/B AAX7683 5.1 62199506 Sufiurinonas denitrif/cans acil XP 504787.1 50554757 Yarrowia /ipolytica ac/ 2 XP_503231.1 5055 1 5 15 Yarrowia /ipolytica SPBCI 703.07 NP_596202.1 191122994 Schizosaccharonces ponbe SPAC22A12.16 NI P593246.1 19114158 Schizosaccharonyces ponbe acl CAB1376165.1 7160185 Sordaria muacrospora acl2 CAB76164.1 7160184 Sordaria macrospora ac/A CBF86850.1 259487849 Aspergi//us niduans ac/B CBF 86848 2594878 8 Aspergillus nidulans [004281 In some organisms the conversion of citrate to oxaloacetate and acetyl-CoA proceeds through a citryl.-CoA intermediate and is catalyzed by two separate enzymes, citryl-CoA synthetase (EC 6.2.1 18) and citryl-CoA Ivase (EC 4.1.3.34) (Aoshima, M,, Appl. Microbiol. Biotechnol. 75:249-255 (2007). Citrvl-CoA synthetase catalyzes the activation of citrate to citryl-CoA. The Hydrogenobacter thermophilus enzyme is composed of large and small subunits encoded by ccsA and ccsB, respectively (Aoshima et al., Mol. Micrbiol. 52:751 -761 (2004)). The citryl-CoA synthetase of Aquijex aeolicus is composed of alpha and beta subunits encoded by sucC/ and sucDl (Hugler et al., Environ. Microbiol. 9:81-92 (2007)). Citry-CoA lyase splits citryl-CoA into oxaloacetate and acetyl-CoA. This enzyme is a homotrimer encoded by cc/ in ivdrogenobacter thermophilus (Aoshinia et a., Mol. Microbiol. 52:763-770 (2004)) and aq_150 in Aquifex aeolicus (Hugler et al., supra (2007)). The genes for this mechanism of -213converting citrate to oxaloacetate and citryl-CoA have also been reported recently in Chlorobiun tepidum (Eisen et al,, PNAS 99(14): 9509-14 (2002)). TABLE 14 Protein GenBank ID GI Number Organism cus A BAD17844.1 46849514 lYdrogenobacter thermopihlus ccsB BAD17846.1 4684951 7 4Hydrogenobacter thermophilu sucC1 AAC07285 2983723 Aquilex aeolicus cc BAD17841 .1 46849510 Bydrogebacr therinophilua aq_150 AAC06486 2982866 Aquifex aeolicus CT0380 NP_661284 21673219 Chlorobium tepidan CT0269 NP 66117 3.1 21673108 Chlorobium tepida CT7834 AA M73 055.1 21647851 Chlorobium tepdum [004291 Citrate lyase (EC4.1.3.6, FIGS. 2 and 3, EB) catalyzes a series of reactions resulting in the cleavage of citrate to acetate and oxaloacetate. In certain embodiments, citrate lyase is expressed in the cytosol of a eukaryotic organism. The enzyme is active under anaerobic conditions and is composed of three subunits: an acyl-carrier protein (ACP, gamma), an ACP transferase (alpha), and an acyl lyase (beta). Enzyme activation uses covalent binding and acetylation of an unusual prosthetic group, 2'-(5"-phosphoribosyl)-3-'-dephospho-CoA, which is similar in structure to acetyl-CoA. Acylation is catalyzed by CitC, a citrate lyase synthetase. Two additional proteins, CitG and CitX, are used to convert the apo enzyme into the active holo enzyme (Schneider et al., Biochemistry 39:9438-9450 (2000)). Wild type E. coli does not have citrate lyase activity; however, mutants deficient in molybdenum cofactor synthesis have an active citrate lyase (Clark, FEMS Microbiol. Lett. 55:245-249 (1990)). The E. coli enzyme is encoded by citEFD and the citrate lyase synthetase is encoded by citC (Nilekani and SivaRaman, Biochemistry 22:4657-4663 (1983)). The Leuconostoc mnesenteroides citrate lyase has been cloned, characterized and expressed in E. coli (Bekal et al., J. Bacteriol. 180:647-654 (1998)). Citrate lyase enzymes have also been identified in enterobacteria that utilize citrate as a carbon and energy source, including Salmonelia typhimurium and K/cbsic/la pneumoniac (Bott, Arch. -214- Microblol. 167: 78-88 (1997); Bott and Dimroth, MoL Microbiol. 14:347-356 (1994)). The aforementioned proteins are tabulated below. TABLE 15 Protein GenBank I) GI Number Organism citF AAC73716.1 1786832 Escherichia coil cite AAC73717.2 87081764 Escherichia coli citD AAC73718.1 1786834 Escherichia coli citC AAC73719.2 87081765 Escherichia coli citG AAC73714 1 1786830 Escherichia coli citX AAC73715.1 1786831 Escherichia coli citF CAA71633. 12842397 Leuconostoc mesenteroides citE CAA71632.1 28421396 Leuconostoc nesenteroides citD CAA7 1635.1 2842395 Leuconostoc nesenteroides citC CAA7 1636.1 3413797 Leuconostoc mesenteroides citG CAA7 1634. 1 2842 398 Leuconostoc mlesenteroides cifX CAA 71634.1 2841398 /Leuconostoc mesenteroides citF Nl_ 459613.1 16763998 SaInionella typhimurium citE AA 19573.1 16419133 Salimonella typhimurium cliD NP 459064.1 16763449 Salmonella typhimurium citC NP 459616.1 16764001 Salmonella typhimurium citG NP 459611.1 16763996 Salmonella typhimurium citX NP 459612.1 16763997 Salmoniella typhimut/am citF CAA56217. 1 565619 Klebsiella pneunoniae citE CAA56216. 1 565618 Klebsiella pneunoniae citD CAA562 15.1 565617 Klebsieliapneumoniae citC BAH66541.1 238774045 Klebsielia pneumoniae

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citG C A A56218.1 565620 Klebs/ella pneunoniae citX AAL60463.1 18140907 Klcbsiella neunoniae -215- [004301 The acylation of acetate to acetyl-CoA is catalyzed by enzymes with acetyl-CoA synthetase activity (FIGS. 2 and 3, F). In certain embodiments, acetyl-CoA synthetase is expressed in the cytosol of a eukaryotic organism. Two enzymes that catalyze this reaction are AMP-forming acetyl-CoA synthetase (EC 6.2.1.1) and ADP-forming acetyl-CoA synthetase (EC 6.2.1.13). AMP-forming acetyl-CoA synthetase (ACS) is the predominant enzyme for activation of acetate to acetyl-CoA. Exemplary ACS enzymes are found in E. coli (Brown et al., J. Gen. Microbiol. 102:327-336 (1977)), Ralstonia eutropha (Priefert and Steinbuchel, J. Bacteriol. 174:6590-6599 (1992)), Methanothermobacter thermautotrophicus (Ingram-Smith and Smith, Archaea 2:95-107 (2007)), Salnonella enterica (Gulick et al., Biochenistry 42:2866-2873 (2003)) and Saccharoniyces cerevisiae (Jogl and Tong, Biochenistry 43:1425-1431 (2004)). TABLE 16 Protein GenBank ID GI Number Organism acs AAC77039.1 1790505 Escherichia coli acoE AAA2 1945.1 141890 Ralstonia eutropha acs I ABC87079.1 8616967 1 Miethanothermohacter thermzautotrophicus acs] AAL23099.1 16422835 Salmonella enterica A CS1 Q 00 574.2 257050994 Saccharomyces cerevisiace 1004311 ADP-forming acetyl-CoA synthetase (ACD, EC 6.2.1.13) is another candidate enzyme that couples the conversion of acyl-CoA esters to their corresponding acids with the concurrent synthesis of ATP. Several enzymes with broad substrate specificities have been described in the literature. ACD I from A rchaeogiobusfu4gidus, encoded by AF121 1, was shown to operate on a variety of linear and branched-chain substrates including acetyl-Co-A, propionyl-CoA, butyryl CoA, acetate, propionate, butyrate, isobutyryate, isovalerate, succinate, fumarate, phenylacetate, indoleacetate (Musfeldt et al., J. Bacteriol. 184:636-644- (2002)). The enzyme from fialoarcula marismortui (annotated as a succinyl-CoA synthetase) accepts propionate, butyrate, and branched-chain acids (isovalerate and isobutyrate) as substrates, and was shown to operate in the forward and reverse directions (Brasen et al,, Arch. Microbiol. 182:277-2287 (2004)). The ACD -216encoded by PAE3250 from hyperthermophilic crenarchaeon Pyrobacuiun aerophiluim showed the broadest substrate range of all characterized ACDs, reacting with acetyl-CoA, isobutyryl CoA (preferred substrate) and phenylacetyl-CoA (Brasen et al, supra (2004)). The enzymes from A. fulgidus, -f. narismortui and P. acrophilun have all been cloned, functionally expressed, and characterized in E. coli (Musfeldt et al., supra; Brasen et al., supra (2004)). Additional candidates include the succinyl-CoA synthetase encoded by sucCD in E, coli (Buck et al., Biochemisiry 24:6245-6252 (1985)) and the acyl-CoA ligase from seidomonas putida (Fernandez-Valverde et al., Appl. Environ. Microbiol. 59:1149-1154 (1993)). Information related to these proteins and genes is shown below. TABLE 17 Protein GenBank ID GI number Organism AF1211 NP 070039.1 11498810 Archaeoglobusfulgidus DSM 4304 AF1983 NP 070807.1 11499565 Archaeoglobusfugidus DSM 4304 scs YP 135572.1 55377722 Haloarcula marismortui ATCC 43049 PAE3250 NP 560604.1 18313937 Pvrobaculun aerophilum str. IM2 sucC NP 415256.1 16128703 Escherichia co/i sucD AAC73823,1 1786949 Escherichia coli paaF AAC24333,2 22711873 Pseudononasputida [004321 An alternative method for adding the CoA moiety to acetate is to apply a pair of enzymes such as a phosphate-transferring acyltransferase and an acetate kinase (FIGS. 2 and 3, F, FIGS. 8E and 8F). This activity enables the net formation of acetyl-CoA with the simultaneous consumption of ATP. In certain embodiments, phosphotransacetylase is expressed in the cytosol of a eukaryotic organism. An exemplary phosphate-transferring acyltransferase is phosphotransacetylase, encoded by pta. The pta gene from F. coli encodes an enzyme that can convert acetyl-CoA into acetyl-phosphate, and vice versa (Suzuki, T. Biochim.Biophys.Acta 191:559-569 (1969)). This enzyme can also utilize propionyl-CoA instead of acetyl-CoA forming propionate in the process (Hesslinger et al. Mo.Microbiol 27:77-492 (1998)). Homologs exist in several other organisms including Salmonella enterica and Chliamvdomonas reinhardii. -217- TABLE 18 Protein GenBank ID GI number Organism Pta NP_416800.1 16130232 Escherichia coli Pta NP 461280.1 16765665 Salmonella enterica subsp. enterica serovar Tvphinnuriun str. L T2 PAT2 XP_001694504.1 159472743 Chlanvdomonas reinhardtii PAT1 X P_001691787.1 159467202 ChaNivclomonas reinhardtii [004331 An exemplary acetate kinase is the E. coli acetate kinase, encoded by ackA (Skarstedt and SilversteinJ.Biol.Chei. 251:6775-6783 (1976)). Homologs exist in several other organisms including Salmonella enterica and Chlamdoionas reinhardtii. Information related to these proteins and genes is shown below: TABLE 19 Protein GenBank ID GI number Organism AckA NP 416799.1 16130231 Escherichia coli AckA NP 461279.1 16765664 Salmonella enterica subsp. enterica serovar Typhinurin str. L.T2 ACK I XP 001694505.1 159472745 Chlanydomonas reinhardtii ACK2 XP_001691682.1 159466992 Chlanivclononas reinhardtii [004341 In some embodiments, cytosolic oxaloacetate is transported back into a mitochondrion by an oxaloacetate transporter. Oxaloacetate transported back into a mitochondrion can then be used in the acetyl-CoA pathways described herein. 1004351 Transport of oxaloacetate from the cytosol to the mitochondrion can be carried out by several transport proteins. Such proteins either import oxaloacetate directly (i.e., oxaloacetate transporter, FIGS. 2i and 81-11) to the mitochondrion or import oxaloacetate to the cytosol while simultaneously transporting a molecule such as citrate (i.e., citrate/oxaloacetate transporter, FIGS. 2C and 8H) from the mitochondrion into the cytosol as shown in FIGS. 2 and 3. -218- Exemplary transport enzymes that carry out these transformations are provided in the table below. TABLE 20 Proteini GenBank I D G1 number ,Organism OACi NP_012802.1 6322729 Saccharomyvces cereviswe S288C Kluvv eronyces lactis NRR L Y KLLA0B12826g XP3 452102.1 50304305 1140 YALIOE04048g XP3_503525.1 50552101 Yarrowia lipoltica CTRG 02239 XP3 002547942. 1 255726032 Candida tropicalis MYA-3404 DCI NP_013452.1 6323381 Saccharomyces cerevisiae S288e YALI 0B03344g X P500457.1 50545838 Yarrowia lipolytica CT RG_02122 XP_002547815,1 255725772 Candida tropicalis MYA-3404 PAS chr4 0877 XP 0024943261 254574434 Pichia pastoris GS115 DTC CAC84549.1 19913113 Arabidopsis thaliana DICI CAC84-545.i 19913105 "icoliana tabacian DTC2 CAC84546.1 19913107 ANicotiana tabacun DTC CAC845 ---- 1 -913109 'N icodiana ta-acuni DTC4 CAC84548.1 19913111 Aicotiana tabacun DTC AAR06239.1 37964368 Citrus junos [004361 In some embodiments, cytosolic oxaloacetate is -first converted to malate by a cytosolic palate dehydrogenase (FIGS. 3H and 8J). Cytosolic malate is transported into a mitochondrion by a malate transporter or a citrate/malate transporter (FIGS. 3 and 8, I). Mitochondrial palate is then converted to oxaloacetate by a mitochondrial malate dehydrogenase (FIGS. 3J and 8K). Mitochondrial oxaloacetate can then be used in the acetyl-CoA pathways described herein. Exemplary examples of each of these enzymes are provided below. [004371 Oxaloacetate is converted into palate by palate dehydrogenase (EC 1. 11.37, FIGS, 3H and 8J). When malate is the dicarboxylate transported from the cytosol to mitochondrion, -. 219-~ expression of both a cytosolic and mitochondrial version of malate dehydrogenase, e.g., as shown in FIG.3, can be used. S. cerevisiae possesses three copies of malate dehydrogenase, MDHI (McAlister-Henn and Thompson, J Bacterio/. 169:5157-5166 (1987), 11DH2 (Minard and McAlister-Henn, Mol. Cell. Biol. 11:370-380 (1991); Gibson and McAlister-lenn, J. Biol Chein. 278:25628-25636 (2003)), and MDH3 (Steffan and McAlister-Henn, J. Biol. Cheim. 267:24708-24715 (1992)), which localize to the mitochondrion, cytosol, and peroxisone, respectively. Close homologs to the cytosolic palate dehydrogenase, MDN2, from S. cerevisiae are found in several organisms including Kiuyveromyces lactis and Candia tropicalis. . co/i is also known to have an active palate dehydrogenase encoded by ndh. TABLE 21 Protein GenBank ID CI Number Organism MDH1 NP_01 2838 6322765 Saccharomyces cerevisiae M/D12 NP_01 45 15 16006499 Saccharomyrces cerevisiae AIDH3 NP_010205 6320125 Saccharonyces cerevisiae AMd? N P_417703 .1 16131 I26 Escherichia coli Kluvveronyces lactis NRRL. Yf KLLA0E07525p XP 454288.1 50308571 1140 YALIOD16753g XP 502909.1 50550873 Yarrowia lipohtica CTRG_ 01021 XP_002546239.1 255722609 Candida tropicalis MYA-3404 [004381 Transport of malate from the cytosol to the mitochondrion can be carried out by several transport proteins. Such proteins either import malate directly (i.e., malate transporter) to the mitochondrion or import malate to the cytosol while simultaneously transporting a molecule such as citrate (i.e., citrate/inalate transporter) from the mitochondrion into the cytosol as shown in FIGS. 2, 3 and 8. Exemplary transport enzymes that carry out these transformations are provided in the table below. TABLE 22 -220- Protein GenBank ID GI number Organism OACI NP 012802.1 6322729 Saccharon yces cerevisae S288c Kluvveronvces lactis NRRL Y KLLA0312826g XP 452102.1 50304305 1140 YALOE04048g XP 503525.1 50521 01 Yarrowia ipolytica CTRG 02239 XP 002547942.1 255726032 Candida tropicais MYA-3404 DIC1 NP 013452.1 6323381 Saccharonyces cerev'isiae S288c YAL IB03344g XP 500457.1 50545838 Yarrowia ipolytica CTR G02122 XP 002547815.1 255725772 Candida tropicalis MYA-3404 PAS chr4_0877 XP 0024943126.1 254574434 Pichia pastoris GS 115 DTC CAC84549.1 19913113 Arabidopsis thaliana DTCI CAC84545.1 19913105 Nicotiana tabacun DTC2 CAC84546.1 19913107 Nicotiana tabacun DTC3 CAC84547.1 19913109 Nicotiana tabacun DTC4 CAC84548.1 19913111 Nicotiana tabacwn DTC AAR06239.1 3964368 Citrusjunos [004391 Malate can be converted into oxaloacetate by malate dehydrogenase (EC 1.1 1 37, FIG. 3, J). When palate is the dicarboxylate transported from the cytosol to mitochondrion, in certain embodiments, both a cytosolie and mitochondrial version of malate dehydrogenase is expressed, as shown in FIG. 3. S. cerevisiae possesses three copies of malate dehydrogenase, MDHI (McAlister-Henn and Thompson, J Bacteriol. 169:5157-5166 (1987), M1DH-2 (Minard and McAlister-Henn, Me. Cell. Biol. 11:370-380 (1991); Gibson and McAlister-Henn, J Biol. Chemt. 278:25628-25636 (2003)), and MDH3 (Steffan and McAlister-Henn, J. Biol. Chem. 267:24708-24715 (1992)), which localize to the mitochondrion, cytosol, and peroxisome, respectively. Close homologs to the mitochondrial palate dehydrogenase, MDH/I, from S, cercvisiae are found in several organisms including Kluyveromyces lactis, Yarrowia lipofytica, Candida tropicalis. E. coli is also known to have an active malate dehydrogenase encoded by mndh. -22 1- TABLE 23 Protein GenBank ID G] Number Organism AM11 NP_012838 6322765 Saccharonyces cerevisiae MVD12 NP 014515 116006499 Saccharonvces cerevisiae MDH3 NP 010205 6320125 .Saccharonces cerevisiae AM/h NP 4177031 16131126 Escherichia coli KLLA0F25960g XP 456236.1 50312405 |uveromyces lactis NRRL Y-1140 YALI0D1753g XP_502909.1 50550873 Yarrowia iipolvtica CYRG 00226 XP 002545445.1 255721021 Candida tropicalis MYA-3404 EXAMPLE II PATHWAYS FOR PRODUCING CYTOSOLAC ACETYL-COA FROM CYTOSOLIC PYRUVATE 1004401 The following example describes exemplary pathways for the conversion of cytosolic pyruvate and threonine to cytosolic acetyl-CoA, as shown in FIG 5. [004411 Direct conversion of pyruvate to acetyl-CoA can be catalyzed by pyruvate dehydrogenase, pyruvate fiorrnate lyase, pyruvate:NAD(P) oxidoreductase or pyruvate:ferredoxin oxidoreductase (FIG. 5H). [004421 Indirect conversion of pyruvate to acetyl-CoA can proceed through several alternate routes. Pyruvate can be converted to acetaldehyde by a pyruvate decarboxylase. Acetaldehyde can then converted to acetyl-CoA by an acylating (CoA-dependent) acetaldehyde dehydrogenase. Alternately, acetaldehyde generated by pyruvate decarboxylase can be converted to acetyl-CoA by the "PDFI bypass" pathway. In this pathway, acetaldehyde is oxidized by acetaldehyde dehydrogenase to acetate, which is then converted to acetyl-CoA by a CoA ligase, synthetase or transferase. In another embodiment, the acetate intermediate is converted by an acetate kinase to acetyl-phosphate that is then converted to acetyl-CoA by a phosphotransacetylase. In yet another embodiment, pyruvate is directly converted to acetyl -222phosphate by a pyruvate oxidase (acetyl-phosphate forming). Conversion of pyruvate to an acetate intermediate can also catalyzed by acetate-forming pyruvate oxidase. [00443] FIG. 5 depicts several pathways for the indirect conversion of cytosolic pyruvate to cytosolic acetyl-CoA (5A/5B, 5A/5C/5D, 5E/5 F/5C/5D, SC/ID). In the first route, pyruvate is converted to acetate by a pyruvate oxidase (acetate forcing) (step A). Acetate can then subsequently converted to acetyl-CoA either directly, by an acetyl-CoA synthetase, ligase or transferase (step B), or indirectly via an acetvl-phosphate intermediate (steps C, D). In an alternate route, pyruvate is decarboxylated to acetaldehyde by a pyruvate decarboxylase (step E). An acetaldehyde dehydrogenase oxidizes acetaldehyde to form acetate (step F). Acetate can then be converted to acetyl-CoA by an acetate kinase and phosphotransacetylase (steps C and D). In yet another route, pyruvate can be oxidized to acetylphosphate by pyruvate oxidase (acetyl phosphate forming) (step G). A phosphotrarisacetylase can then convert acetylphopshate to acetyl-CoA (step D). [004441 Cytosolic acetyl-CoA can also be synthesized from threonine by expressing a native or heterologous threonine aidolase (FIG. 5J) (van Maris et a], AEM 69:2094-9 (2003)). Threonine aldolase can convert threonine into acetaldehyde and glycine. The acetaldehyde product can then be converted to acetyl-CoA by various pathways described above. [004451 Gene candidates for the acetyl-CoA forming enzymes shown in Figure 5 are described below. [00446] Pyruvate oxidase (acetate-forming) (FIG. 5A) or pyruvate:quinone oxidoreductase (PQO) can catalyze the oxidative decarboxylation of pyruvate into acetate, using ubiquione (EC 1.2.5.1) or quinone (EC 1.2.2. 1) as an electron acceptor. The E. coli enzyme, PoxB, is localized on the inner membrane (Abdel-Hamid et at., Microbiol 147:1483-98 (2001)). The enzyme has thiamin pyrophosphate and flavin adenine dinucleotide (FAD) cofactors (Koland and Gennis. Biochemistry 21:4438-4442 (1982)); O'Brien et al., Biochemistry 16:3105-3109 (1977); O'Brien and Gennis, J. Biol. Chem. 255:3302-3307 (1980)). PoxB has similarity to pyruvate decarboxylase of S. cerevisiae and Zymjomfonas mobilis. 'i he pqo transcript of Corynebacteriwn glutainicun encodes a quinone-dependent and acetate-forming pyruvate oxidoreductase -223- (Schreiner et al.,JBacteriol 188:1341-50 (2006)). Similar enzymes can be inferred by sequence homology. TABLE 24 Protein GenBankID GI Number Organism poxB NP 415392.1 16128839 Escherichia co/i pqo YP 226851.1 62391449 Corvnebacterium glutamicum poxB YP 309835.1 74311416 Shigella sonne poXB ZP 03065403.1 194433121 Shigela dysenteriae [004471 The acylation of acetate to acetyl-CoA (FIG. 5B) can be catalyzed by enzymes with acetyl-CoA synthetase, ligase or transferase activity. Two enzymes that can catalyze this reaction are AMP-fonning acetyl-CoA synthetase or ligase (EC 6.2.1.1) and ADP-forming acetyl-CoA synthetase (EC 6.2. 1,13). AMP-forming acetyk-CoA synthetase (ACS) is the predominant enzyme for activation of acetate to acetyl-CoA. Exemplary ACS enzymes are found in k coli (Brown et al., . Gen. Microbiol. 102:327-336 (1977)), Ralstonia eutropha (Priefert and Steinbuchel, J Bacteriol. 174:6590-6599 (1992)), Methanothermobacter thermautotrophicus (Ingram-Smith and Smith, Archaea 2:95-107 (2007)), Salmonella enterica (Gulick et al., Biochemistry 42:2866-2873 (2003)) and Saccharomyces cerevisiae (Jogl and Tong, Biochemistry 43:1425-1431 (2004)). ADP-forning acetyl-CoA synthetases are reversible enzymes with a generally broad substrate range (Musfeldt and Schonheit, ,. Bacteriol. 184:636 644 (2002)). Two isozymes of ADP-forming acetyl-CoA synthetases are encoded in the Archaeoglobus fu/gdus genome by are encoded by AF 1211 and AF1983 (Musfeldt and Schonheit, supra (2002)). The enzyme from Haloarcula narismortui (annotated as a succinyl CoA synthetase) also accepts acetate as a substrate and reversibility of the enzyme was demonstrated (Brasen and Schonheit, Arch. Mficrobiol. 182:277-287 (2004)). The ACD encoded by P4E3250 from hyperthermophilic crenarchaeon Pyrobaculum aeroph ilun showed the broadest substrate range of all characterized ACDs, reacting with acetate, isobutyryi-CoA (preferred substrate) and phenylacetyl-CoA (Brasen and Schonheit, supra (2004)). Directed evolution or engineering can be used to modify this enzyme to operate at the physiological temperature of the host organism. The enzymes from A.fulgidus, H. marisnortui and P. aerophilum have all been cloned, functionally expressed, and characterized in E. coli (Brasen -224and Schonheit, supra (2004); Musfeldt and Schonheit, supra (2002)). Additional candidates include the succinyl-CoA synthetase encoded by sucCD in E. coli (Buck et al., Biochemistrv 24:6245-6252 (1985)) and the acyl-CoA ligase from Pseudonionas putida (Fernandez-Valverde et al., AppI. Environ. Aicrobiol. 59:1149-1154 (1993)). The aforementioned proteins are shown below. TABLE 25 Protein GenBank ID (A Number Organism acs AAC77039.1 1790505 Escherichia coli acoE AAA21945. 1 141890 Ralstonia eutropha acs] ABC87079.1 86169671 Methanothermobacter theriautotrophicus acsI AAL23099.1 16422835 Sahnonella enterica ACS! Q01574.2 257050994 Saccharomyces cerevisiae AFT211 NP 070039.1 11498810 Archaeoglobusfulgidus AF1983 NP 070807.1 11499565 Archaeoglobusf ugidus scs YP 135572.1 55377722 Haloarcula narismnortui PAE32S0 NP 560604.1 18313937 Pvrobaculun aerophiHn str. IM2L sucC NP 415256.1 16128703 Escherichia colt sucD AAC73823.1 1786949 Eschcrichia col paaF _______AAC2187Pseudononas puitia 1004481 The acylation of acetate to acetyl-CoA can also be catalyzed by CoA transferase enzymes (FIG. 5B). Numerous enzymes employ acetate as the CoA acceptor, resulting in the formation of acetyl-CoA. An exemplary CoA transferase is acetoacetyl-CoA transferase, encoded by the E. coil atoA (alpha subunit) and atoD (beta subunit) genes (Korolev et al., Acra Crstaflour.. Biol.Crvstaiiogr. 58:2116-2121 (2002); Vanderwinkel etal., 33:902-908 (1968)). This enzyme has a broad substrate range (Sramek et al., Arch Biochemi Biophys 171:14-26 (1975)) and has been shown to transfer the CoA moiety to acetate from a variety of branched and linear acyl-CoA substrates, including isobutyrate (Matthies et al., Appl Environ.Microbiol 58:1435-1439 (1992)), valerate (Vanderwinkel et al.. Biochen.Biophys.Res.Conunun. 33:902 908 (1968)) and butanoate (Vanderwinkel et al., Biochem.Biophs.Rs.Conun. 33:902-908 (1968)). Similar enzymes exist in Corynebacteruman autamicun ATCC 13032 (Duncan et al.. 68:5186-5190 (2002)), Clostridiun acetobutylicun (Cary et al., Appl Environ AMicrobiol 56:1576-1583 (1990); Wiesenborn et al., App! Environ Microbiol 55:323-329 (1989)), and

-L

Clostridiun saccharoperbutylacetonicut (Kosaka et al., Biosci.Biotechnol Biochem. 7 1: 5 8-68 (2007)). TABLE 26 Gene AcCession No Organism atoA 2492994 P76459.1 Escherichia coli atoD 2492990 P76458.1 Escherichia coli actA 62391407 YP 226809. 1 Coionnebacteriumt ghtamicuwm eg0592 62389399 YP 22480L 1 Corynebacteriwnglutamicum ctfA 15004866 NP 149326.1 Clostridium acetobutiyicum ctfB 15004867 NP 149327.1 Clostridium acetobutvlicum ctfA_ 31075384 AAP42564.1 Clostridiwn saccharoerbuvacetonzcum ctfB_ 31071538_ AAP412565.1 Clostridiunn saccharopebatpacetoncum 1004491 Acetate kinase (EC 2.7.2.1) can catalyzes the reversible ATP-dependent phosphorylation of acetate to acetylphosphate (FIG. 5C). Exemplary acetate kinase enzymes have been characterized in many organisms including E. coli, Clos tridium acetobutylicum and Methanosarcina thermophila (Ingram-Smith et al., J. Bacteriol. 187:2386-2394 (2005); Fox and Roseman,. Biot. Chen. 261:13487-13497 (1986); Winzer et al., Microbioloy 143 (Pt 10):3279 3286 (1997)). Acetate kinase activity has also been demonstrated in the gene product of E. coli parT (Marolewski et al., Biochemistry 33:2531-2537 (1994). Some butyrate kinase enzymes (EC 2 .7.2.

7 ), for example buk1 and b/k2 from Clostridium acetobutylicum, also accept acetate as a substrate (Hartmanis, M.G., J. Biol. Chen. 262:617-621 (1987)). Homologs exist in several other organisms including Salmonella enterica and Chlamydomonas reinhardtui. TABLE 27 Protein GenBank ID GI Number Organism ackI NP 416799.1 16130231 Escherichia coli Ack AAB1 8301,1 1491790 Clostridiun acetobutlicum Ack A AA 72 0421 349834 Methanosarcina thermophila pur T AAC74919.1 1788155 Escherichia coli bak N1P 349675 15896326 Clostridlam acetobutylicam buk 2 Q97111 0137415 Clostridiu m acetobutvlicun ackA NP 461279.1 16765664 Salmonella nphimurtum ACKI XP 001694505.1 159472745 Chiamy'domonas reinharatii ACK XP 001691682.1 159466992 Chlamyononas reinhardii -226- [004501 The formation of acetyl-CoA from acety-iphosphate can be catalyzed by phosphotransacetylase (EC 2.3.1 .8) (FIG. 5D), The pta gene from E. coli encodes an enzyme that reversibly converts acetyl-CoA into acetyl-phosphate (Suzuki, T., Biochim. Bioph.ys. Acta 191:559-569 (969)). Additional acetyltransferase enzymes have been characterized in Bacillus subtilis (Rado and Hoch, Biochin. Biophys. A cta 321:114-125 (1973), Clostridium k/u yveri (Stadtman, E., Methods EnzVmol. 1:5896-599 (1955), and Thermotoga naritina (Bock et at., Bacteriol. 181:1861-1867 (1999)). This reaction can also be catalyzed by some phosphotranbutyrylase enzymes (EC 2.3.1.19), including the ptb gene products from Clostridiun acetobutylicum (Wiesenborn et al., Ap Environ. Microbial. 55:3 1 7-322 (1989); Walter et al., Gene 134:107-111 (1993)). Additional ptb genes are found in butyrate-producing bacterium L2 50 (Louis et al., J. Bacterial. 186:2099-2106 (2004) and Bacillus megaterium (Vazquez et al., Curr. Microbiol. 42:345-349 (2001). Homologs to the E. colipta gene exist in several other organisms including Salmonella enterica and Chlaiydomonas reinhardtii. TABLE 28 Protein GenBanklID GIl Number Organism Pta NP 416800.1 71152910 Escherichia coli Pta P39646 730415 Bacillus subti/is Pta A 5N 80 1 146346896 Clostridiun kluvveri Pta Q9X L4 6685776 Thermotoga maritime Ptb NP P349676 3 4 5 4 048 4 Clostridium acetobutylicum Pth AA R19757,1 38425288 butyrate-producing bacterium L2-50 Ptb CAC07932.1 10046659 Bacillus nmegaterium Pta NP 461280.1 16765665 Sahmone/a enterica subsp. enterica serovar TyphNiurium str. L T2 PA T2 XP 001694504,1 159472743 Chlamvdomonas reinhardti PAT1 XP 001691787.1 159467202 Chliamvdomonas reinhardtii [004511 Pyruvate decarboxylase (PDC) is a key enzyme in alcoholic fenrmentation, catalyzing the decarboxylation of pyruvate to acetaldehyde. The PDC1 enzyme from Saccharonyces cerevsiae has been extensively studied (Killenberg-Jabs et al., Eur.J.Biochen. 268:1698-1704 (2001); Li et a]., Biochemistry. 38:10004-10012 (1999); ter Schure et al., AppI.Environ.Microbiol. 64:1303-1307 (1998)). Other well-characterized PDC enzymes are found in Zymomonas mobilus (Siegert et al., Protein Eng Des Sel 18:345-357 (2005)), Acetobacterpasteurians (Chandra et al., 176:443-451 (2001)) and Kluyveronyces lactis -227- (Krieger et al., 269:3256-3263 (2002)). The PDCI and PDC-5 enzymes of Saccharonyces cerevisiae are subject to positive transcriptional regulation by PDC2 (l-Iohrnann et al, 11ol Gen Genet 241:657-66 (1993)). Pyruvate decarboxylase activity is also possessed by a protein encoded by CTRG 03826 (GI:255729208) in Candida tropicalis, PDCI (GI number: 1226007) in KIuveronyces lactis, YALIOD10131g (GI:50550349) in Yarrowia lipolytica, PAS chr3 0188 (GI:254570575) in Picha pastoris, pyruvate decarboxylase (GI: ii: 159883897) in 5chizosaccharoiycL espom be, ANI_ 1 _1024084 (Gi:145241548), ANI_1 _796114 (GI:317034487), ANI1 _936024 (GI:317026934) and ANI_1 _2276014 (G1:317025935) in Aspergillus niger. TABLE 29 Protein GenBank ID GI |Oranisrn Number Ed_ P0672.1 118391 Z _vn8ononas niobilis pdcI P06169 30923 172 Saccharomnyces cerevisiae Pdc,2 -NP 010366.1 6320286 Saccharoivces cerev. .sz .ae Pdc5 NP 013235.1 6323163 Saccharonyces cerevisiae CTRG_ 03826 XP 002549529 255729208 Candida tropicalis CU329670. 1:585597.587312 CAA90807 159883897 Schizosaccharonvces porn be YALIOD1 0131 g XP 502647 50550349 Yarrowia 1/polyvtca PAS chr3 0188 XP 002492397 254570575 Pichia pastors pdc Q81388 20385191 Acetobacter pasteurans pdcl Q12629 52788279 Kuynveronvces lactis ANI 1 1024084 XP 001393420 145241548 Aspergillus niger ANI1_796114 XP 001399817 317026934 Aspergillus niger ANI 1 936024 XP 001396467 317034487 Ispergillus niger ANTI 1 2276014 NP 001388598 317025935_ Aspergti niger [004521 Aldehyde dehydrogenase enzymes in EC class 1.2 1 catalyze the oxidation of acetaldehyde to acetate (FIG. 5F). Exemplary genes encoding this activity were described above. The oxidation of acetaldehyde to acetate can also be catalyzed by an aldehyde oxidase with acetaldehyde oxidase activity. Such enzymes can convert acetaldehyde, water and 02 to acetate and hydrogen peroxide. Exemplary aldehyde oxidase enzymes that have been shown to catalyze this transformation can be found in Bos taurus and Mus nusculus (Garattini et al., Cell Mol Life Sci 65:1019-48 (2008): Cabre et al., Biochem Soc Trans 15:882-3 (1987)). Additional -228aldehyde oxidase gene candidates include the two flavin- and molybdenum- containing aldehyde oxidases of Zea mays, encoded by zmA0-i and znAO-2 (Sekimoto et at., J Biol Chen 272:15280-85 (1997)). TABLE 30 Gene GenBank Accession No. GI No. Organism zmAO-1 NI_001105308.1 162458742 Zea inavs zmAO-2 BAA23227.1 2589164 Zea mavs Aox1 054754.2 20978408 I us'nusculus _XDH______ DAA24801. 296182686 Bo auus 1004531 Pyruvate oxidase (acetyl-phosphate forming) can catalyze the conversion of pyruvate, oxygen and phosphate to acetyl-phosphate and hydrogen peroxide (FIG. 5G). This type of pyruvate oxidase is soluble and requires the cofactors thiamin diphosphate and flavin adenine dinucleotide (FAD). Acetyl-phosphate forming pyruvate oxidase enzymes can be found in lactic acid bacteria Lactobacillus delbrueckii and Lactobacillus plantarun (Lorquet et al., , Bacteriol 186:3749-3759 (2004); Hager et al., Fed Proc 13:734-38 (1954)). A crystal structure of the L. plantarum enzyme has been solved (Muller et al., (1994)). In Streptococcus sanguints and Streptococcus pneumonia, acetyl-phosphate forming pyruvate oxidase enzymes are encoded by the spxB gene (Spellerberg et al., Mol Micro 19:803-13 (1996); Ramos-Montanez et al., Mol Micro 67:729-46 (2008)). The SpxR was shown to positively regulate the transcription of spxB in S. pneuinoniae (Ramos-Montanez et al., supra). A similar regulator in S. sanguinis was identified by sequence homology. Introduction or modification of catalase activity can reduce accumulation of the hydrogen peroxide product. TABLE 31 Gene GenBank Accession No. GI No. Organism poxYB NP 786788.1 28379896 Lactobacillus plantarum spxB8 L39074.1 1161269 Streptococcus pneuniomae Spd_0969 YP_ 816445.1 1165171-39 Streptococcus pneunonzae (spxR) spxB ZP 07887723.1 315612812 Streptococcus sanguinis spxR ZP_07887944.1 G 1: 3 15613 033 Streptococcus sanguinis -229- [004541 The pyruvate dehydrogenase (PDH) complex can catalyze the conversion of pyrivate to acetyl-CoA (FIG. 5HF). The E. coli PDI complex is encoded by the genes aceEF and lpdA. Enzyme engineering efforts have improved the E. coli PDH enzyme activity under anaerobic conditions (Kim et al., J. Bacteriol. 190:3851-3858 (2008); Kim et at., Appl.Environ.Microbiol. 73:1766-1771 (2007); Zhou et al., Biotechnol.Lett. 30:335-342 (2008)). In contrast to the E. coli PDH, the B. subtilis complex is active and required for growth under anaerobic conditions (Nakano et al., 179:6749-6755 (1997)). The Klebsiella pneumoniae PDH, characterized during growth on glycerol, is also active under anaerobic conditions (Menzel et al., 56:135-142 (1997)). Crystal structures of the enzyme complex from bovine kidney (Zhou et al., 98:14802-14807 (2001)) and the E2 catalytic domain from Azotobacter vinelandii are available (Mattevi et aL. Science. 255:1544-1550 (1992)). Some mammalian PD-1 enzymes complexes can react on alternate substrates such as 2-oxobutanoate. Comparative kinetics of Rattus norvegicus PDH and BCKAD indicate that BCKAD has higher activity on 2-oxobutanoate as a substrate (Paxton et al., Biochem.J. 234:295-303 (1986)). The S. cerevisiae complex canconsist of an E2 (LA T7) core that binds El (PDA 1, PDBI), E3 (LPD1), and Protein X (PDXI) components (Pronk et al., Yeast 12:1607-1633 (1996)). TABLE 32 Gee Acession No. G1 Number Organism aceE NP 414656,1 16128107 Escherichia coli aceF NP 414657.1 16128108 Escherichia coli lpd NP 414658,1 16128109 Escherichia coli pdhA P2188 1 1 312.3 238 Bacillus subtilis pdhB P21 882.1 129068 Bacillus subtilis pdhC P21883.2 1 29054 Bacilhlus subtilis pdhD P2 1880.1 118672 Bacillus subtilis aceE YP 001333808.1 1 52968699 Klebsiella pneumonia aceF YP 001333809. 152968700 Klebsiella nnenoa _P4 _P 001333810.1 152968701 _Kebsielia pneunonia Pdhal NP 001004072.2 124430510 | Rattus norvegicus Pdha2 NP 446446,1 16758900 Rattus norvegicus D)at NP_112287.1 78365255 Rattus norvegicus DId NP_955417,1 40786469 Rattus norvegicus LA T7 N1P 014328 63242 58 Saccharonyces cerevisiae PDAI NP 011105 37362644 Saccharonyces cerevisiac -230 PDI NP 009780 6319698 Saccharomyces cerevisiae LPD1 N1P_ 116635 14318501 Saccharomvces cereviszae PlAY] NP 011709 632162_) Saccharomces cerevisiac [004551 As an alternative to the large multienzyme PDH complexes described above, some organisms utilize enzymes in the 2-ketoacid oxidoreductase family (OFOR) to catalyze acylating oxidative decarboxylation of 2-keto-acids. Unlike the dehydrogenase complexes, these enzymes contain iron-sulfur clusters, utilize different cofactors, and use ferredoxin or flavodixin as electron acceptors in lieu of NAD(P)-1. Pvruvate ferredoxin oxidoreductase (PFOR) can catalyze the oxidation of pyruvate to fonm acetyl-CoA (FIG. 5H). The PFOR from Desulfovibrio africanus has been cloned and expressed in . coli resulting in an active recombinant enzyme that was stable for several days in the presence of oxygen (Pieulle et al., JBacteriol. 179:5684 5692 (1997)). Oxygen stability is relatively uncommon in PFORs and is believed to be conferred by a 60 residue extension in the polypeptide chain of the D. africanus enzyme. The Ml. thermoacetica PFOR is also well characterized (Menon et al., Biochemistry 36:8484-8494 (1997)) and was even shown to have high activity in the direction of pyruvate synthesis during autotrophic growth (Furdui et al., JBIol Chem. 275:28494-28499 (2000)). Further, F. coi possesses an uncharacterized open reading frame, ydbK, that encodes a protein that is 51% identical to the l thernioacetica PFOR. Evidence for pyruvate oxidoreductase activity in F col has been described (Blaschkowski et al., Eur.J Biochem. 123:563-569 (1982)). Several additional PFOR enzymes are described in Ragsdale, Chem.Rev. 103:2333-2346 (2003). Finally, flavodoxin reductases (e.g., fqrB from lielicobacter pylori or Campylobacterjejuni (St Maurice et al., J.Bacteriol. 189:4764-4773 (2007))) or Rnf-type proteins (Seedorf et at., Proc.Nat.Acad.Sci. US.A. 105:2128-2133 (2008); Herrmann et aL, J.Bacteriol. 190:784-791 (2008)) provide a means to generate NADH or NADPFH from the reduced ferredoxin generated by PFOR. These proteins are identified below. TABLE 33 Protein GenBank ID GI Number Organism Por CAA70873.1 1770208 Desultbvibrio africanus Por YP 428946.1 83588937 Moorelia thernoacetica vd1bK NP 415896.1 16129339 Escherichia coli ft ______NP 2079 5 _5._1 15645778 _ _ilicobacter pylon -231- Protein GenBank ID GI Number Organism frB YP 001482096.1 1 57414840 Canpylobacterjejuni RJf EDK33306.1 146346770 Clostridiun kluyveri Rn/E EDK33307.1 146346771 Clostridiun kluyveri Rn~fG FDK3')3 308.1 1 46 346772 Ciostrkaun 1hiuvver1' Rn/P EDK33310.1 146346774 Clostridium uiyveri Rn/B EDK33311.1 146346775 Clostridium kuy'veri [00456] Pyruvate formate-lyase (PFL, EC 2.3.1.54) (FIG. 51), encoded by p/LB in t coli, can convert pyruvate into acetyl-CoA and formate. The activity of PFL can be enhanced by an activating enzyme encoded by p/lA (Knappe etta. ProcNal.Acad Sc US.A 81:1332-1335 (1984); Wong et al., Biochenistrv 32:14102-14110 (1993)). Keto-acid formiate-lyase (EC 2.3. 1.

) also known as 2-ketobutyrate formate-lyase (KFL) and pyruvate formate-lyase 4, is the gene product of tdcE in E. coli. This enzyme catalyzes the conversion of 2-ketobutyrate to propionyl CoA and fonnate during anaerobic threonine degradation, and can also substitute for pyruvate formate-lvase in anaerobic catabolism (Simanshu et al., JBiosci. 32:1195-1206 (2007)). The enzyie is oxygen-sensitive and, like PflB, can require post-translational modification by PFL AlE to activate a glycyl radical in the active site (Hesslinger et al., Mol,.Microbio 27:477-492 (1998)). A pyruvate fornmate-lyase from A rchaeg/ubusf#lgidus encoded by pj/D has been cloned, expressed in E. coli and characterized (Lehtio et al., Protein Eng Des Sel 17:545-552 (2004)). The crystal structures of the A. figidus and '. coli enzymes have been resolved (Lehdo et al.,. JMol.Biol. 357:221-235 (2006); Leppanen et aL, Structure. 7:733-744 (1999)). Additional PL. and PFL-AE candidates are found in Lactococcus lactis (Melchiorsen et al., App! !Vficrobiol Biotechnol 58:338-344 (2002)), and Streptococcus nutans (Takahashi-Abbe et al., Oral.MAicrobiol inmunol. 18:293-297 (2003)), Chlamiydomonas reinhardtii (Hemschemeier et al., Eukaryot.Cell 7:518-526 (2008b); Atteia et al., .J.Biol.Chenm. 281:9909-9918 (2006)) and Clostridiun pasteurianum (Weidner et al, J Bacteriol 178:2440-2444 (1996)). TABLE 34 Protein GenBank ID GI Number Organism ptlB N1 415423 16128870 Escherichia coli p//A NP 415422.1 16128869 Escherichia col; tdcE AAT48170.1 48994926 Escherichia coli -232pfD N P 070278.1 11499044 Archaegiubusfidgicus p CAA03993 2407931 Lactococcus lactis P _ _ _ BAA09085 1129082 S'trptoCoCCS gi titans PFL_ XP 001689719A1 159462978 C lanvdononas reinhardtii p//A] XP 001700657.1 159485246 Chlamydomonas reinhardtii N7 Q46266.1 2500058 Clostri dimnpasteurianum act CAA63749.1 1072362 Clostridiun pasteurianun [004571 The NAD(P) dependent oxidation of acetaldehyde to acetyl-CoA (FIG. 51) can be catalyzed by an acylating acetaldehyde dehydrogenase (EC 1.2. 1.10). Acylating acetaldehyde dehydrogenase enzymes of . coli are encoded by achE, eutE, and whpF (Ferrandez et al, J Bacterio/ 179:2573-81 (1997)). The Pseuclomnonas sp. CF600 enzyme, encoded by dnpi, participates in meta-cleavage pathways and forms a complex with 4-hydroxy-2-oxovalerate aldolase (Shingler et al, J Bacteriol 174:711 -24 (1992)). Solventogenic organisms such as Clostridiun acetobutv/icun encode bifunctional enzymes with alcohol dehydrogenase and acetaldehyde dehydrogenase activities. The bifunctional C. acetobulicum enzyrnes are encoded by bdh I and adhE2 (Walter, et al., J. Bacteriol. 174:7149-7158 (1992); Fontaine et al., J.Bacteriol. 184:821-830 (2002)). Yet another candidate for acylating acetaldehyde dehydrogenase is the aid gene from Clostriciun beijerincki (Toth, Appi. Environ. Aicrobiol. 65:4973-4980 (1999). This gene is very similar to the eutE acetaldehyde dehydrogenase genes of Salmonella typhinuriun and E. coli (Toth, Appl. Environ. Microbiol. 65:4973-4980 (1999). TABLE 35 Protein GenBank ID GI Number | Organism adhE NP 415757.1 16 129202 Escherichia coli mhpF NP_414885.1 | 16128336 Ebscherichia coli c/mpF CAA43226.1 | 45683 | Pseudomonas sp. CF600 adIhE2 AA K09379.1 12958626 C ostridiun acetobutvlicum bdh I N P 349892.1 | 15-896543 Clostridiwn acetobutylicum AI AAT 6643 6 | 4947 3535 C ostridium beijerinckii eutE NP 416950 16130380 Escherichia coli eutE AA A80209 |687645 Sahnonel/a typhimurium [004581 Threonine aldolase (EC 4.1 .2.5) catalyzes the cleavage of threonine to glycine and acetaldehyde (FIG. 5J). The Saccharonyces cerevisiae and Candida albicans enzymes are encoded by GLY I (Liu et al, Eur J Biochem 245:289-93 (1997); MvlcNeil et al, Yeast 16:167-75 -233- (2000)). The ItaE and glyA gene products of K coli also encode enzymes with this activity (Liu et al, Eur J Biochem 255:220-6 (1998)). TABLE 36 Protein GenBank tD GI Number (Jr----------------------0 gan-isni----------------- GLY! -TINP 010868.1 6320789 Saccharonvces cerevtszae GL Y] AAB64198.1 2282060 Candida albicans taE AAC73957.1 1787095 Escherichia coli gyA AAC75604.1 1788902 Escherichia coli EXAMPLE II PATHWAYS FOR INCREASING CYTOSOLIC ACETYL-COA FROM MITOCHONDRIAL AND PEROXI SONAL ACETY L-COA BY CARN I NE MEIDATED TRANSLOCATION [004591 This example describes pathways for the carnitine-mediated translocation of acetvl CoA from mitochondria and peroxisomes to the cytosol of a eukaryotic cell. [004601 Acetyl-CoA is a key metabolic intermediate of biosynthetic and degradation pathways that take place in different cellular compartments. For example, during growth on sugars, the majority of acetyl-CoA is generated in the mitochondria, where it feeds into the TCA cycle. During growth on fatty acid substrates such as oleate, acetyl-CoA is formed in peroxisomes where the beta-oxidation degradation reactions take place. A majority of acetyl-CoA is produced in the cytosol during growth on two-carbon substrates such as ethanol or acetate. The transport of acetyl-CoA or acetyl units among cellular compartments is essential for enabling growth on different substrates. [004611 One approach for increasing cytosolic acetyl-CoA is to modify the transport of acetyl CoA or acetyl units among cellular compartments. Several mechanisms for transporting acetyl CoA or acetyl units between cellular compartments are known in the art. For example, many eukaryotic organisms transport acetyl units using the carrier molecule carnitine (van Roermund et al., EMBO J 14:3480-86 (1995)). Acetyl-carnitine shuttles between cellular compartments have been characterized in yeasts such as Candida albicans (Strijbis et al, J Biol Chem -234- 285:24335-46 (2010)). In these shuttles, the acetyl moiety of acetyl-CoA is reversibly transferred to carnitine by acetylcarnitine transferase enzymes. Acetylcarnitine can then be transported across the membrane by acetylcarnitine/carnitine translocase enzymes. After translocation, the acetvl-CoA can be regenerated by acetylcarnitine transferase. [004621 Exemplary acetylcarnitine translocation pathways are depicted in Figure 6. In one pathway, mitochondrial acetyl-CoA is converted to acetylcarnitine by a mitochondrial carnitine acetyltransferase (step A). Mitochondrial acetylearnitine can then be translocated across the mitochondrial membrane into the cytosol by a mitochondrial acetylcarnitine translocase (step D). A cytosolic acetylcarnitine transferase regenerates acetyl-CoA (step C). Peroxisomal acetyl CoA is converted to acetylcarnitine by a peroxisomal acetylcarnitine transferase (step 13), Peroxisomal acetylcarnitine can then be translocated across the peroxisomal membrane into the cytosoi by a peroxisomal acetylcarnitine translocase (step E), and then converted to cytosolic acetyl-CoA by a cytosolic acetylcarnitine transferase (step C). [004631 While some yeast organisms such as Candida albicans synthesize carnitine Ce novo, others organisms such as Saccharonyces cerevisiae do not (van Roermund et al., EMBO) J 18:5843-52 (1999)). Organisms unable to synthesize carnitine de novo can be supplied carnitine exogenously or can be engineered to express a one or more carnitine biosynthetic pathway enzymes, in addition to the acetyltransferases and translocases required for shuttling acetyl-CoA from cellular compartments to the cytoplasm. Carnitine biosynthetic pathways are known in the art. In Cand/ida albicans, for example, carnitine is synthesized from trimethyl-L-lysine in four enzymatic steps (Strijbis et al., FASEB J23:2349-59 (2009)). 1004641 Enzyme candidates for carnitine shuttle proteins and the carnitine biosynthetic pathway are described in further detail in below. [004651 Carnitine acetyltransferase (CAT, EC 2.3.1.7) reversibly links acetyl units from acetyl-CoA to the carrier molecule, carnitine. Cand/ida albicans encodes three CAT isozymes: Cat2, Yat1 and Yat2 (Strijbis et al., JBiol Chein 285:24335-46 (2010)). Cat2 is expressed in both the mitochondrion and the peroxisomes, whereas Yatl and Yat2 are cytosolic. The Cat2 transcript contains two start codons that are regulated under different carbon source conditions. -235- The longer transcript contains a mitochondrial targeting sequence whereas the shorter transcript is targeted to peroxisomes. Cat2 of Saccharonees cerevisiae and AcuJ of Aspergillus nidulans employ similar mechanisms of dual localization (Elgersma et al., EIBO J 14:3472-9 (1995); Hynes et al., Euk Cell 10:547-55 (2011)). The cytosoiic CAT of A. nidulans is encoded byficC. Other exemplary CAT enzymes are found in Rattus norvegicus and Homo sapiens (Cordente et al., Biochem 45:6133-41 (2006)). Exemplary carnitine acyltransferase enzymes (EC 2.3.1.21) are the Cptl and Cpt2 gene products of Rattus norvegicus (de Vries ct al., Biochem 36:5285-92 (1997)). TABLE 37 Protein Accession # GI number Organism Cat2 AAN3 1660.1 23394954 Canaida albicans Eat AAN3 165 9 233 9 4952 Candida albicans Yatz XP 711005.1 68490355 Candida albicans Cat CA-A88327. 1 683665 Saccharomyces cerevisae YaI AAC09495. 1 456138 Saccharomvces cerevisiae Yat2 Nl_010941.1 6320862 Saccharomyces cerevisiae Acu CBF69795.1 259479509 Aspergillus nidulans FacC A AC82487.1 - 2511761 Aspergilius nidulans CI at AAH83616.1 53733439 Rattus norvegicus c rat P43155.5 215274265 Holmo sapiens Opt] AAB48046.1 1850590 Rattus norvegicus Opt______1AAB0239 3478_4 Rattus norvegics [004661 Carnitine-acetylcamitine translocases can catalyze the bidirectional transport of carnitine and carnitine-fatty acid complexes. The Cact gene product provides a mechanism of transport across the mitochondrial membrane (Ramsay et al Biochim Biophys Acta 1546:21-42 (2001)). A similar protein has been studied in humans (Sekoguchi et al., J Biol Chem 278:38796-38802 (2003)). Th Saccharom yces cerevisiae mitochondrial carnitine carrier is Crci (van Roermund et al., supra; Palmieri et at., Biochinica et Biophys Acta 1757:1249-62 (2006)). The human carnitine translocase was able to complement a Cre -deficient strain of S. cerevisiae (van Roermund et al., supra). Two additional carnitine translocases found in Drosophila melanogaster and C aenorhabditis elegans were also able to complement Crc1 deficient yeast (Oey et al., Mol Genet Metab 85:121-24 (2005)). Four mitochondrial -236carnitine/acetvlcarnitine carriers were identified in TrVpanosoma brucei based on sequence homology to the yeast and human transporters (Colasante et aL, Mo1 Bioch em Parasit 167:104 117 (2009)). The camitine transporter of Cand/ida albicans was also identified by sequence homology. An additional mitochondrial carnitine transporter is the acuH gene product of Aspergiluis nidutlans, which is exclusively localized to the mitochondrial membrane (Lucas et al., FEMS Microbiol Lett 201:193-8 (2006)). TABLE 38 Gact P97521 1 2497984 Rattus norvegicus CacI NP 0010344444.1 86198310 loina sapiens CaO19.2851 XP 715782.1 68480576 Candida albicans Cc Ip NP 014743,1 6324674 Saccharonyces cerevisiae Di 1 CAA88283.1 829102 Caenorhabdits elegans Colt CAA73099,1 1944534 Drosophila melanogaster Tb 11.02.2960 EAN79492. 1 70833990 Tryanosona brucei Tb11.03.0870 EAN79007.1 70833505 Trypanosoma bruce Tb 11.01.5040 EAN80288.1 70834786 Trpanosoma brucei Tb92T8 5810 AAX69329 . 1 62175181 Trvpanosonza brued acu _ _ CAB44434.151905_ _ _ pergilius niulans [004671 Transport of carnitine and acetylcarnitine across the peroxisomal membrane has not been well-characterized. Specific peroxisomal acetylcarnitine carrier proteins in yeasts have not been identified to date. It is possible that mitochonidrial carnitine translocases also function in the peroxisomal transport of carnitine and acetylcarnitine. Alternately, the peroxisomal membrane can be permeable to carnitine and acetyicarnitine. Experimental evidence suggests that the OCTN3 protein of Mus musculus is a peroxisomal carnitine/acylcarnitine transferase. [004681 Yet another possibility is that acetyl-CoA or acetyl-carnitine is transported across the peroxisomal or mitochondrial membranes by an acetyl-CoA transporter such as the Pxal and Pxa2 ABC transporter of Saccharom.Yces cerevisiae or the ALDP ABC transporter of HOo sapiens (van Roermund et al., FASER J22:4201-8 (2008)). Pxal and Pxa2 form a heterodimeric complex in the peroxisomal membrane and transport long-chain acyl-CoA esters (Verleur et al., Eur J Biochem 249: 657-61 (1997)). The mutant phenotype of a pxal/pxa2 deficient yeast can -237be rescued by heterologous expression of ALDP, which was shown to transport a range of acyl CoA substrates van Roermund et al., FASEB 224201-8 (2008)). TABLE 39 Protein Accession # GI number Organism Oc TNV3 BAA78343.1 4996131 Mus musculus PxaI AAC49009.1 619668 Saccharonyces cerevisiae Pxa2 AA1351597.1 1931633 Saccharomyces cerevisiae ALDP NP 000024.2 7262393 Homo sapiens [004691 The four step carnitine biosynthetic pathway of Cand/ida albicans was recently characterized. The pathway precursor, trimethyllysine (T ML), is produced during protein degradation. TML dioxygenase (CaO13.4316) hydroxylates TML to forn 3-hydroxy-6-N trimethyllysine. A pyridoxal-5'-phoshpate dependent aldolase (CaO 19.6305) then cleaves HTML into 4-trimethyaminobutyraldehyde. The 4-trimethylaminobutyraldehyde is subsequently oxidized to 4-trimethylaminobutyrate by a dehydrogenase (CaO 1 9.6306). In the final step, 4-trimethylaminobutyrate is hydroxylated to form carnitine by the gene product of Ca019. 7131. Flux through the carnitine biosynthesis pathway is limited by the availability of the pathway substrate and very low levels of carnitine seem to be sufficient for nonnal carnitine shuttle activity (Strejbis et al., IHBMB Life 62:357-62 (2010)). TABLE 40 Protein Accession # GI number Organism CaO19.4316 XP 720623.1 6847075 5 Candida albicans Ca019.6305 XP 711090.1 68490151 Candida albicans CaO19.6306 XP 711091.1 68490153 Candida albicans CaO]9.7]31 XP 715182.1 68481628 Candida albicans [00470] Organisms unable to synthesize carnitine de novo can uptake carnitine front the growth medium. Uptake of carnitine can be achieved by expression of a carnitine transporter such as Agp2 of S. cerevisiae (van Roermund et al., supra). -238- TABLE 41 _ Protein ______... _Agggssigon _ ___ _------------ . GI number__ _ _ _Organism ,P 2____ _NP 00969. ____6319608_____ Sac haronlcs cerevisiae EXAMPLE IV PATHWAYS FOR PRODUCING 1,3-BUTANEDIOL FROM ACETYL-COA [00471] 1,3-BDO production can be achieved by several alternative pathways as described in FIG. 4. All pathways first convert two molecules of acetyl-CoA into one molecule of acetoacetyl-CoA employing a thiolase. Acetoacetyl-CoA thiolase converts two molecules of acetyl-CoA into one molecule each of acetoacetyl-CoA and CoA (step A, FIG. 4). Exemplary acetoacetyl-CoA thiolase enzymes include the gene products of atoB from K coli (Martin et al., Nat. Biotechnol. 21 :796-802 (2003), thA and th/B from C. acetobutyicwn ([lanai et al., Appl Environ. Microbiol. 73:7814-7818 (2007); Winzer et al.,]J. Mol. Microbiol. Biotechnol. 2:531 541 (2000), and ERG10 from S. cerevisiae (Hiser et al.,]. Biol. Chein. 269:31383-31389 (1994). The acetoacetyl-CoA thiolase from Zoogloea ranigera is irreversible in the biosynthetic direction and a crystal structure is available (Merilainen et al, Biochen 48: 11011-25 (2009)). TABLE 42 Protein GenBank ID GI number O rganism ------------------------------------------------------------------------------------------------ + --------------------------------------------- A toB NP_416728 16130161 Escherichia coli ThA NP 349476.1 15896127 Clostridiwn acetobutv/icun Th21B N P 149242.1 15004782 Clostridiuni acetobutVicum ER G10 NP_ 0 15297 6325229 Saccharonvces cerevisiae phbA P07097.4 135759 Zoogloea ram igera [00472] Acetoacetyl-CoA reductase (step -1, FIG. 4) catalyzing the reduction of acetoacetyl CoA to 3-hydroxybutyryl-CoA participates in the acetyl-CoA fermentation pathway to butyrate in several species of Clostridia and has been studied in detail (Jones and Woods, !ficrobiol. Rev. 50:484-52-4 (1986)). The enzyme from Clostridiun acetobutyicun, encoded by hbd, has been -239cloned and functionally expressed in F. coli (Youngleson et aL, J. Bacterial. 171:6800-6807 (1989)). Additionally, subunits of two fatty acid oxidation complexes in E. coli, encoded by fheB and thI.j, function as 3-hydroxyacyl-CoA dehydrogenases (Binstockand Schulz, Methods Enznol. 71 Pt C:403-411 (1981)). Yet other gene candidates demonstrated to reduce acetoacetyl-CoA to 3-hydroxybutyryl-CoA are phbB from Zoogloea ramigera (Ploux et al., Eur. J. Biochein. 174:177-182 (1988) andphaB from Rhoelobacter sphaeroides (Alber et al., Hol. Microbiol. 61:297-309 (2006), The former gene candidate is NADP[I-dependent, its nucleotide sequence has been determined (Peoples and Sinskey, Mol. Microbial. 3:349-357 (1989) and the gene has been expressed in E. coli. Substrate specificity studies on the gene led to the conclusion that it could accept 3-oxopropionyl-CoA as a substrate besides acetoacetyl-CoA (Ploux et at., Eur. J. Biochen. 174:177-182 (1988)). Additional gene candidates include HblI (C-terminal domain) and Hbd2 (N-terminal domain) in Clostridliwn kiuvveri (Hillmer and Gottschalk, Biochim. Biophys. Acra 3334:12-23 (1974)) and HSD17B10 in Bos taurus (Wakil et al., . Biol. Chen. 207:631-638 (1954)). TABLE 43 Protein Genbank ID GI number Organism thdB P2 1177 2 119811 Escherichia co/i fac/2J P7399.1 3334437 Escherichia coli Hbd2 ED I)K 34807.1 14634827 1 Clostriditun kiuvveri Hb/i EDK3 25 1 2.1 146345976 Clostriciun k/duveri Hbdi P5204 1.2 C/os tridliun acetobutyicum HSD1717B0 002691.3 3183024 Bos Taurus pnbB P 2322 3)8.1 1 30017 Zooa/oea rand-r phall_ _ P 3538251 _ 77464321 Rhoeobacter spharoid/es [004731 A number of similar enzymes have been found in other species of C/ostrid/ia and in Metallosphaera seedu/a (Berg et al., Science 318:1782-1786 (2007). TABLE 44 Protein GenBank ID GI number Organism Hibc NP 349314.1 NP 349314.1 Clostridiun acetobutvlicwn -240- Hbd AAMV14586.1 A AM 14586. 1 Clostridium beijerinckii Mlsed_1423 YP_001 191505 YP_001191505 Metallosphaera sedula Msed 0399 YP 001190500 YP 001190500 Mlfetallosphaera secula Msed 0389 YP 001190490 YP 001190490 M1etallosphaera sedula Msed 1993 YP 001192057 YP 001192057 Metallosphaera sedula [004741 Several acyl-CoA dehydrogenases are capable of reducing an acyl-CoA to its corresponding aldehyde (Steps E, I, FIG. 4). Exemplary genes that encode such enzymes include the Acinetobacter calcoaceticus acr1 encoding a fatty acyl-CoA reductase (Reiser and Somerville, J. Bacteriol. 179:2969-2975 (1997), the Acinetobacter sp. -14 fatty acyl-CoA reductase (Ishige et al., Appl. Environ. Microbial. 68:1192-1195 (2002), and a CoA- and NADP dependent succinate semialdehyde dehydrogenase encoded by the sucD gene in Clostridiun kuyveri (Sohling and Gottschalk, J. Bacterial. 178:871-880 (1996); Sohling and Gottschalk, J. Bacterial. 1778:871-880 (1996)). SucD of P. gingivalis is another succinate semialdehyde dehydrogenase (Takahashi et al. J. Bacterial. 182:4704-4710 (2000), The enzyme acylating acetaldehyde dehydrogenase in Pseudomonas sp, encoded by bphG, is yet another candidate as it has been demonstrated to oxidize and acylate acetaldehyde, propionaldehyde, butyraldehyde, isobutyraldehyde and formaldehyde (Powlowski et al., J. Bacterial. 175:377-385 (1993)). In addition to reducing acetyl-CoA to ethanol, the enzyme encoded by adhE in Leuconostoc mesenteroides has been shown to oxidize the branched chain compound isobutyraldehyde to isobutyryl-CoA (Kazahaya et al., J. Gen. Appi. Microbial. 18:45-55 (1972); Koo et al.. Biotechnot Lett. 27:505-510 (2005)). Butyraldehyde dehydrogenase catalyzes a similar reaction, conversion of butyryl-CoA to butyraldehyde, in solventogenic organisms such as Clostridiuni saccharopcrbuty/acetonicum (Kosaka et at., Biosci. Biotechnol. Biochen. 11:58-68 (2007)). Additional aldehyde dehydrogenase enzyme candidates are found in Desulatibacillun alkenivorans, Citrobacter koseri, Salmonella enterica. Lactobacillus brevis and Bacillus selenitireducens. -241- TABLE 45 Protein GenBank ID GI number Organism acH Y P 047869.1 50086355 Acinetobacter calcoaceticus acr! AAC45217 1684886 Acinetobacter baylyi acr BAB85476.1 18857901 4cinetobacter sp. Strain M-1 sucD P'38947.1 172046062 Clostridium kluyveri sucD INP 904963.1 34540484- Porphyrononas gingivalis bphG BAA03892.1 425213 Pseudoionas sp adhE AAV66076.1 55818563 Leuconostoc mesenteroides Bid AAP42563.1 31075383 Clostridiuni saccharoperbutyiacetonicum Aid AC L0665 8.1 218764192 Desuljitibacillum alkenivorans AK-0 Aid Y1 001452373 157145054 Citrobacter koseri A TCC BA A-895 pduP NP 460996.1 1676538 1 Sahnonella enterica Tphinurium pduP AB164680.1 116099531 Lactobacillus brevis A TCC 367 BselDRAFT 1651 ZP 02169447 163762382 Bacillus selenitireducens MLS1O [004751 An additional enzyme type that converts an acyl-CoA to its corresponding aldehyde is malonyl-CoA reductase which transforms malonyl-CoA to malonic semialdehyde. Malonyl-CoA reductase is a key enzyme in autotrophic carbon fixation via the 3-hydroxypropionate cycle in thermoacidophilic archacal bacteria (Berg et al., Science 318:1782-1786 (2007); Thauer, Science 318:1732-1733 (2007)). The enzyme utilizes NADPH as a cofactor and has been characterized in Mietallosphaera and Sulfblobus spp (Alber et al., J. Bacterial. 188:8551-8559 (2006); Hugler et al., J. Bacterial. 184:2404-2410 (2002)). The enzyme is encoded by Msed_0709 in Aletallosplaera sedula (A [ber et al., supra (2006); Berg et al., Science 318:1782-1786 (2007)) A gene encoding a malonyl-CoA reductase from Sulfblobus tokodaii was cloned and heterologously expressed in K coli (Alber et al., J. Bacterial. 188:8551-8559 (2006)). This enzyme has also been shown to catalyze the conversion of methylmalonyl-CoA to its corresponding aldehyde (WO 2007/141208 (2007)) Although the aldehyde dehydrogenase functionality of these enzymes is similar to the bifunctional dehydrogenase from Chlorolexus -242aurantiacus, there is little sequence similarity. Both malonyl-CoA reductase enzyme candidates have high sequence similarity to aspartate-semiialdehyde dehydrogenase, an enzyme catalyzing the reduction and concurrent dephosphorylation of aspartyl-4-phosphate to aspartate semialdehyde. Additional gene candidates can be fund by sequence homology to proteins in other organisms including Sulblobus soifataricus and Sulblobus acidocaldarius and have been listed below. Yet another candidate for CoA-acylating aldehyde dehydrogenase is the atd gene from Clostridium beijerinckii (['oth et al., App. Environ. Microbiol. 65:4973-4980 (1999). This enzyme has been reported to reduce acetyl-CoA and butyryl-CoA to their corresponding aldehydes. This gene is very similar to eutEU that encodes acetaldehyde dehydrogenase of Salmonella typhinurium and E. coli (Toth et al., supra). TABLE 46 Protein GenBank ID GI number Organism Msed 0709 YP 001190808.1 146303492 Afetallosphaera sedula Mcr NP 378167.1 15922498 Sulfolobus tokodail auS C" - NP -- 3435631 15898958 Suilbiobus soiataricuts Saci_2370 YP_256941.1 70608071 Sutfilobus acidocaldarius Ald AAT6643 6 947353 5 Clostridium beijerinciii eutE AAA80209 687645 Salmonella typhniuriun eutE P77445 2498347 Escherichia coli [00476] Exemplary genes encoding enzymes that catalyze the conversion of an aldehvde to alcohol (i.e., alcohol dehydrogenase or equivalently aldehyde reductase) (steps C and G of FIG. 4) include alrA encoding a medium-chain alcohol dehydrogenase for C2-C14 (Tani et al., Appl. Environ. Microbiol., 66:5231-5235 (2000)). ADH2 from Saccharomyces cerevisiae (Atsumi et al., Nature, 451:86-89 (2008)), VhD from E. coli which has preference for molecules longer than C3 (Sulzenbacher et al., J. of Aolecular Biology, 342:489-502 (2004)), and bdh I and bc/h II from C. acetobutvlicum which converts butyraldehyde into butanol (Walter et al., J of Bacteriology, 174:7149-7158 (1992)). The gene product of yghD catalyzes the reduction of acetaldehyde, malondialdehyde, propionaldehyde, butyraidehyde, and acrolein using NADPH as -243the cofactor (Perez et al., J. Biol. Chen., 283:7346-7353 (2008)). The adhiA gene product from Zvmononas mobilis has been demonstrated to have activity on a number of aldehydes including formaldehyde, acetaldehyde, propionaldehyde, butyraldehyde, and acrolein (Kinoshita et al. Apple. Microbiol, Biotechnol, 22:249-254 (1985)). Additional aldehyde red uctase candidates are encoded by bdh in C. saccharoperbutylacetonicwn and Chei_1722, Chei_2181 and Cbe!_2421 in C. belierinckii. TABLE 47 Protein GenBank ID GI number Organism alrA BAB1 2273.1 9967138 Acinetobacter sp. strain M-I ADH2 NP 014032.1 6323961 Saccharowyces cerevislae yahD NP 417484.1 16130909 Escherichia coli c/h I NP 3498921 15896543 Clostriiun acetobuttlcUwn Ac/h I NP 349891 1 15896542 Clostridun acetobuttlcum ac/hA YP_162971,1 56552 132 Zvmomonas mobilis bc/h BAF4N463.i 124221917 Ciosridium saccharoperbutylacetonicum Chel 1722 Y1P 001308850 150016596 Clostricium beijerinckii Chei 2181 Y P 001309304 150017050 Clostricln beijerinckii Chei 2421 Y'P 001309535 150017281 Clostric/ium beijerinckii [00477] Enzymes exhibiting 4-hydroxybutyraldehyde reductase activity (EC 1 .1.61) also fall into this category. Such enzymes have been characterized in Ralstonia eutropha (Bravo et al., J. Forensic Sci., 49:379-387 (2004)), Clostricmn kinyveri (Wolff et al., Protein Expr. Purif, 6:206-212 (1995)) and A,-abidopsis thaliana (Breitkreuz et al., . BioL Cheat, 278:41552-41556 (2003)). Yet another gene is the alcohol dehydrogenase; adhI from Geobacillus thermoglcosidasius (Jeon et al., J Biotechnol., 135:127-133 (2008)). TABLE 48 Protein GenBank ID GI number Organism 4hbd YP 726053.1 113867564 Ralstonia eutropha H16 4hbd L21902.1 146348486 Clostridian k/ayvveri DSM 555 -244- 4hbc! Q94B07 1524980N Arabic/opsis thaliana ad/l AA R91477,1 40795502 Geobacillus thermoglucosidasius M10EXING [004781 Another exemplary enzyme is 3-hydroxyisobutyrate dehydrogenase which catalyzes the reversible oxidation of 3-hydroxyisobutyrate to methylmalonate semialdehyde. This enzyme participates in valine, leucine and isoleucine degradation and has been identified in bacteria, eukaryotes, and mammals. The enzyme encoded by P84067 from Therm us therniophilus HB8 has been structurally characterized (Lokanath et at., J. Mat. Biol., 352:905-917 (2005)). The reversibility of the human 3-hydroxyisobutyrate dehydrogenase was demonstrated using isotopically-labeled substrate (Manning et al, Biocheni J., 231:481-484 (1985)). Additional genes encoding this enzyme include 3hidh in Homo sapiens (Hawes et al., Methods Enzymzol, 324:218-228 (2000)) and Oryctolags cuniculus (Hawes et al., supra; Chowdhury et al., Biosci. Biotechnol Biochen., 60:2043-2047 (1996)), mmsB in Pseudomnonas aeriginosa and Pseudonmonas putida (Liao etal., US patent 20050221466), and dihat in Psecudomnasputida (Aberhart et al., J. Chem. Soc., 6:1404-1406 (1979); Chowdhury et al., supra; Chowdhury et al. Biosci. Biotechnol Biochen. 67:438-441 (2003)). TABLE 49 Protein GenBank ID GI number Organism P84067 P84067 75345323 Thernas thermoa phi/us 3hich P3 1937.2 12643395 Homno sapiens 3hidh P32185.1 416872 Oryctolagus cun icu/us nnsf P28811 .1 12721 1 Pseudomnonas aeriginosa nunsB NP_746775.1 26991350 Pseudoionas putida dhat Q59477.1 242618 Pseudoinonas putida [00479] Exemplary two-step oxidoreductases that convert an acyl-CoA to alcohol (e.g., steps B and J of FIG. 4) include those that transform substrates such as acetyl-CoA to ethanol (e.g., adhE from E. coli (Kessler et al., FES Lett. 281:59-63 (1991)) and butyryl-CoA to butanol (e.g. adhE2 from C. acetobutylicun (Fontaine et al., J. Racteriol. 184:821-830 (2002)). In addition to reducing acetyl-CoA to ethanol, the enzyme encoded by adhE in Leuconostoc nesenteroides has -245been shown to oxidize the branched chain compound isobutyraldehyde to isobutyryl-CoA (Kazahava et al, J. Gen. Appl. Microbiol. 18:43-55 (1972); Koo et al., Biotechnol. Lett. 27:505 510 (2005). T ABLE 50 Protein GenBank ID GI number Organism adhE NP 4157571 16129202 Escherichia coli adhE2 AAK09379.1 12958626 Clostridium acetobutylicuni adhE AAV66076.1 55818563 Leuconostoc mesenteroides [004801 Another exemplary enzyme can convert malonyl-CoA to 3-HP. An NADPH dependent enzyme with this activity has characterized in Chloroflexus aurantiacus where it participates in the 3-hydroxypropionate cycle (Hugler et al., J. Bacteriol. 184:2404-2410 (2002); Strauss and Fuchs, Eur. J. Biochem. 21 5:633-643 (1993). This enzyme, with a mass of 300 kDa is highly substrate-specific and shows little sequence similarity to other known oxidoreductases (Hugler, supra (2002)). No enzymes in other organisms have been shown to catalyze this specific reaction: however there is bioinformatic evidence that other organisms can have similar pathways (Klatt et al., Environ. Microbiol. 9:2067-2078 (2007)). Enzyme candidates in other organisms including Roselflexus castenholzil, Erythrobacter sp. NAP1 and marine gamma proteobacterium HTCC2080 can be inferred by sequence similarity. TABLE 51 Protein GenBank ID ( number Organism Rcas 2929 YP 0014330091 156742880 Roseiflexus castenholzil NAP] 02720 ZP_01039179.1 85708113 Erythrobacter sp. A4P1 MGP2080 00535 ZP 01626393.1 119504313 marine gamma proteobacterium HTCC2080 1004811 Longer chain acyl-CoA molecules can be reduced by enzymes such as the jojoba (Sinnondsia chinensis) FAR which encodes an alcohol-forming fatty acyl-CoA reductase. Its -246overexpression in E. coli resulted in FAR activity and the accumulation of fatty alcohol (Metz et a., Plant Physiol. 122 635-644 (2000)). TABLE 52 Protein GenBa-nk-f- -- D GI number --Organismn FAR AAD'38039.1 5020215 Simmiondsia chinensi s [004821 There exist several exemplary alcohol dehydrogenases that convert a ketone to a hydroxyl functional group (e.g., steps D, F and 0 of FIG. 4). Two such enzymes from E. coli are encoded by malate dehydrogenase (mdih) and lactate dehydrogenase ( Ih) in addition, lactate dehydrogenase from Ralstonia eutropha has been shown to demonstrate high activities on substrates of various chain lengths such as lactate, 2-oxobutyrate, 2-oxopentanoate and 2 oxoglutarate (Steinbuchel and Schlegel, Eur.. Biochemn. 130:329-334 (1983)). Conversion of the oxo functionality to the hydroxyl group can also be catalyzed by 2-keto 1,3-BDO reductase, an enzyme reported to be found in rat and in human placenta (Suda et al., Arch. Biochemu. Biophys. 176:610-620 (1976); Suda etal., Biochen. Biop.hys. Res. Comnmun. 77:586-591 (1977)). An additional candidate for these steps is the mitochondrial 3-hydroxybutyrate dehydrogenase (bch) from the human heart which has been cloned and characterized (Marks et al., .J. Biol. Chem. 267:15459-15463 (1992)). TABLE 53 Protein GenBank ID GI number Organism Ahdh AAC76268.1 1789632 Escherichia coli icdhi NP 415898.1 16129341 Escherichia coi Ldh YP_725182.1 113866693 RaLstonia eutropha Bc/h AAA58352.1 177198 Hono sapiens [00483] Additional exemplary enzynmes can be found in Rhodococcus ruber (Kosjek el al., Biotechnol Bioeng. 86:55-62 (2004)) and rIococcus jtriosus (van der et al., Eur..J.Biochem. 268:3062-3068 (2001)). For example, secondary alcohol dehydrogenase enzymes capable of this -247transformation include adIh from C. beijerinckil (Hanai et at., App! Environ Microbio0 73:7814 7818 (2007); Jojima et al., App! Microbiol Biotechnol 77:1219-1224 (2008)) and ad/h from Thernoanaerobacter brockii (Hanai et al., App Environ Microbio! 73:7814-7818 (2007); Peretz et al., Anaerobe 3:259-270 (1997)). The cloning of the bdhA gene from Rhizobiun (Sinorhizobiun) Meliloti into K coli conferred the ability to utilize 3-hydroxybutyrate as a carbon source (Aneja and Charles, J. Bacteriol. 181(3):849-857 (1999)). Additional candidates can be found in Pseudoionasfragi (Ito et at., J. Mol. Biol. 355(4) 722-733 (2006)) and Ralstonia pickettii (Takanashi et al., Antonie van Leeuwenoek, 95(3.):249-262 (2009)). Information related to these proteins and genes is shown below. TABLE 54 Protein GenBank]ID GI number Orgatnism Sadh CAD36475 21615553 Rhodococcus rubber Ad/A AAC25556 3288810 Pvrococcusfucriosus Ah P 14941.1 113443 Thermoanaerobobacter brockii Adh AAA 23 199 2 60592974 Clostridium beijerinckii Rd/hA NP 437676.1 16264884 Rhizobium (Sinorhizobhium) Meliloti PRK13394 BAD86668.1 57506672 Pseudononasfragi Bdhi BAE72684.1 84570594 Ralstonia pickettii iBdh2 BA E72685.1 84570596 Ralstonia pickettii Bdh3 BAF91602.1 158937170 Ra/stonia pickettii [00484] Acetoacetyl-CoA:acetyl-CoA transferase (i.e., step K, FIG. 4) naturally converts acetoacetyl-CoA and acetate to acetoacetate and acetyl-CoA. This enzyme can also accept 3 hydroxybutyryl-CoA as a substrate or could be engineered to do so (i.e., step Ni, FIG. 4). Exemplary enzymes include the gene products of atoAD front E. coli (Hanai et al., Appl Environ Microbiol 73:7814-7818 (2007)), ctpIB from C. acetobutilicum ( Jojima etal., App/AMicrobio! Biotechno! 77:1219-1 224 (2008)), and ct/AR from Closiridium saccharoperbutylacetonicum -248- (Kosaka et al., Biosci.Biotechnol Biochem. 71:58-68 (2007)). Information related to these proteins and genes is shown below. TABLE 55 Protein GenBank ID A number Organism A toA P76459.1 2492994 Escherichia coli AtoD P76458.1 2492990 Escherichia coli CtIfA NP 149326.1 15004866 Clostridium acetobutylicum Ctf N P149327 1 15004867 Clostidium acetobutylicun Ct1/A A-AP42564.1 31075384 Clostridiun saccharoperbutylacetonicumn CrfB A AP425 65.1 3 107 5 3 8 5 Clostridiwn saccharoperbutlacetonicui [004851 Succinyl-CoA:3-ketoacid-CoA transferase naturally converts succinate to succinyl CoA while converting a 3-ketoacvl-CoA to a 3-ketoacid. Exemplary succinyi-CoA :3 :ketoacid CoA transferases are present in Helicobacterpvlori (Corthesy-Theulaz et al., J.Biol.Chem. 272:25659-25667 (1997))-Bacillus subtilis (Stols et al, ProteinE p.Purif 53:396-403 (2007)), and Homo sapiens (Fukao et al., Genomics 68:144-151 (2000); Tanaka et al., MolU un.Reprod. 8:16-23 (2002)). Information related to these proteins and genes is shown below. TABLE 56 Protein GenBan k H) GI number Organism HPAG]_0676 YP_627417 108563101 Helicobacter pvlori HPAGI 0677 Y P 627418 108563102 He licobacter piylori ScoA NP 391778 16080950 Bacillus subtilis ScaB NP 3917771 16080949 Bacillus subtijis OXVCTI NP 0004l27 4557817 Hono sapienS OXCT2 NP 071403 11545841 Homo sapiens [00486] Additional suitable acetoacetyl-CoA and 3-hydroxybutyryl-CoA transferases are encoded by the gene products of cal, cat2, and cat3 of Clostridium kluvveri. These enzyrnes -249have been shown to exhibit succinyl-CoA, 4-hydroxybutyryl-CoA, and butyryl-CoA acetyltransferase activity, respectively (Seedorf et al., Proc. Nat. Acad 0 . Sci. USA 105:2128-2133 (2008); Sohling and Gottschalk, JBactcriol 178:871-880 (1996)). Similar CoA transferase activities are also present in Trichonionas vaginalis' (van Grinsven et al., J. Biol. Chem. 283:1411-1418 (2008)) and Trvpanosona bracei (Riviere ct al., J. Biol. Chem. 279:45337-45346 (2004)). Yet another transferase capable of the desired conversions is butyryl-CoA:acetoacetate CoA-transferase. Exemplary enzymes can be found in Pusobacerium nuclea.tum (Barker et aL., J. Bacteriol. 152(i):201-7 (1982)), Clostridtin SB4 (Barker et al., J. Biol. Chem. 253(4):1219 25 (1978)), and Clostridiam acetobuty4icu (Wiesenborn et al., AppL Environ. Microbiol. 55(2):323-9 (1989)). Although specific gene sequences were not provided for butyryl CoA:acetoacetate CoA-transferase in these references, the genes FN0272 and FN0273 have been annotated as a butyrate-acetoacetate CoA-transferase (Kapatral et al., J. Bact. 184(7) 2005-2018 (2002)). Homologs in Fusobacterium nucleatum such as FNI 857 and FN 1856 also likely have the desired acetoacetyl-CoA transferase activity. FN1857 and FN1856 are located adjacent to many other genes involved in lysirie fermentation and are thus very likely to encode an acetoacetate:butyrate CoA transferase (Kreimeyer, etal.,J. BioL Chew. 282 (10) 7191-7197 (2007)). Additional candidates from Porphyrmonas gingivalis and Thermoanaerobacter tengcongensis can be identified in a similar fashion (Kreimeyer, et al.,J. Biol. Chew. 282 (10) 7191-7197 (2007)). Information related to these proteins and genes is shown below. TABLE 57 Protein GenBank ID GI number Organism Catl P38946.1 729048 Clostridian ktuyveri Cat2 P38942.2 1705614 Clostridiunt kluveri Cat3 EDK35586.1 146349050 Clostridiun kluyveri TV-G 395550 XP 001330176 123975034 Trichomonas vaginalis G3 ThI 1.02.0290 X P_828352 71754875 Trypanosoma bruce FNO2 72 NP 603 179.1 19703617 Fusobacterin nucleatam FNO/273 NP 603180.1 19703618 Fusobacterium nucatum FN/I85 7 NP 602657.1 19705162 Fusobacterium nucleatun -250- [I56NP 602656.1 19705S161 Fuiso bateriuni nucleatuio PG106 NP 9052 8L1 34540802 Poh >ronionas ginWgalis R783 PG1075 NP 905290.1 34540811 Porphyromonas gingivalis WF83 TTE07 20 NP 622378.1 20807207 Thermoanaerobacter tengcongensis M1B4 TiE0721 NP 622379.1 20807208 Thermoanaerobacter tengcongensis MB4 [004871 Acetoacetyl-CoA can be hydrolyzed to acetoacetate by acetoacetyl-CoA hydrolase (step K, F 1G. 4). Similarly, 3-hydroxybutyryl-CoA can be hydrolyzed to 3-hydroxybutyate by 3 hydroxvbutyryl-CoA hydrolase (step M, FIG. 4). Many CoA hydrolases (EC 3.1.2.1) have broad substrate specificity and are suitable enzymes for these transformations either naturally or following enzyme engineering. Though the sequences were not reported, several acetoacetyl CoA hydrolases were identified in the cytosol and mitochondrion of the rat liver (Aragon and Lowenstein, J. Blo. Chem. 258(8):4725-4733 (1983)). Additionally, an enzyme from Ratus norvegicus brain (Robinson et al., Biochen. Biophys. Res. Conunun. 71:959-965 (1976)) can react with butyryl-CoA, hexanoyl-CoA and malonyl-CoA. The acot12 enzyme from the rat liver was shown to hydrolyze C2 to C6 acyl-CoA molecules (Suematsu et al., Eur. J. Biochen. 268:2700-2709 (2001)). Though its sequence has not been reported, the enzyme from the mitochondrion of the pea leaf showed activity on acetyl-CoA, propionyl-CoA, butyryl-CoA, palmitoyl-CoA, oleoyl-CoA, succinyl-CoA, and crotonyl-CoA (Zeiher and Randall, Plant.Physiol. 94:20-27 (1990)). Additionally, a glutaconate CoA-transferase from A cidanm inococcus fermentans was transformed by site-directed mutagenesis into an acyl-CoA hydrolase with activity on glutaryl-CoA, acetyl-CoA and 3-butenoyl-CoA (Mack and Buckel, FEBSLett. 405:209-212 (1997)). This indicates that the enzymes encoding succinyl-CoA:3 ketoacid-CoA transferases and acetoacetyl-CoA:acetyl-CoA transferases can also be used as hydrolases with certain mutations to change their function. The acetyl-CoA hydrolase, ACH1, from S. cerevisiae represents another candidate hydrolase (Buu et al., JBiolChen. 278:17203 17209 (2003)). Information related to these proteins and genes is shown below. -251- TABLE 58 Protein GenBank ID GI number Organism Acot12 NP 570103.1 18543355 Rattus norvegicus GctA CAA57199 559392 Acidauzinococcusfrrmntans GctBF CAA5 7200 559393 Acidaminococcusfozrenntans ACHI NP 009538 6319456 Saccharomyces cerevislae [004881 Another hydrolase is the human dicarboxylic acid thioesterase, acot8, which exhibits activity on glutaryl-CoA, adipyl-CoA, suberyl-CoA, sebacyl-CoA, and dodecanedioyl-CoA (Westin et al., J. Biol. Chen. 280:38125-38132 (2005)) and the closest E. coli homolog, tesB, which can also hydrolyze a broad range of CoA thioesters (Naggert et al., J Biot. Chew. 266:11044-11050 (1991)) including 3-hydroxybutyryl-CoA (Tseng et al. Apple. Environ. Mlicrobiol. 75(10):3137-3145 (2009)). A similar enzyme has also been characterized in the rat liver (Deana, Biochen. Int. 26:767-773 (1992)). Other potential E. coli thioester hydrolases include the gene products of tesA (Bonner and Bloch, J. Biol. Chem. 247:3123-3133 (1972)), ybgC (Kuznetsova et at., FEMS Microbiol. Rev. 29:263-279 (2005); Zhuang et al., FEBS Let. 516:161-163 (2002)), paal (Song et al., J BIol Chem. 281:11028-11038 (2006)), and yhdB (Leduc et al., J Bacteriol. 189:7112-7126 (2007)). Information related to these proteins and genes is shown below. TABLE 59 Protein GenBank ID GI number Organism Acot8 CAA1 5502 3191970 lono sapiens TesB NP 414986 16128437 Escherichia coli A cot8 NP 570112 51036669 Rattus norvegicus TesA NP 415027 16128478 Escherichia coli YbgC NP 415264 16128711 Escherichia coli Paal NP 415914 16129357 Escherichia coli YbdB NP 415129 16128580 Escherichia coli -252 - [004891 Additional hydrolase enzymes include 3-hydroxyisobutyryl-CoA hydrolase which has been described to efficiently catalyze the conversion of 3-hydroxyisobutyryi-CoA to 3 hydroxyisobutyrate during valine degradation (Shimomura et al., J. RioL Chem. 269:14248 14253 (1994)). Genes encoding this enzyme include hibch of Rattus norvegicus (Shimomura et al., supra (1994); Shimomura et al., Methods EnzYinol 324:229-240 (2000)) and Hono sapiens (Shirnornura et aL, supra (1994). Candidate genes by sequence homology include hibch of Saccharomvces cerevisiae and BC 2292 of Bacillus cereus. BC 2292 was shown to demonstrate 3-hydroxybutyryl-CoA hydrolase activity and function as part of a pathway for 3 hydroxybutyrate synthesis when engineered into Escherichia coli (Lee et aL, App!. ficrobiol. Biotechnol. 79:633-641 (2008)). Infonnation related to these proteins and genes is shown below. TABLE 60 Protein GenBank I D GI number Organism H[itch Q5XIE6.2 146324906 Ra.tus norvegicus Hibch | Q6NVY1.2 146324905 iHono sapiens fich | P28817.2 2506374 Saccharonyces cerevisiae BC_1292 AP09256 29895975 Bacillus cereus A TCC 14579 1004901 An alternative method for removing the CoA moiety from acetoacetyl-CoA or 3 hydroxybutyryl-CoA (steps K and M of FIG 4) is to apply a pair of enzymes such as a phosphate-transferring acyltransferase and a kinase to impart acetoacetyl-CoA or 3 hydroxybutyryl-CoA synthetase activity. This activity enables the net hydrolysis of the CoA ester of either molecule with the simultaneous generation of ATP. For example, the butyrate kinase (buk)/phosphotransbutyrylase (pth) system from Clostridiun acetobutyiicuin has been successfully applied to remove the CoA group from 3-hydroxybutyryl-CoA when functioning as part of a pathway for 3-hydroxybutyrate synthesis (Tseng et al., Appl. Environ. Microbiol. 75(10):3137-3145 (2009)). Specifically, the ptb gene from C. acetobutylicum encodes an enzyme that can convert an acyl-CoA into an acyl-phosphate (Walter et al. Gene 134(1): p. 107 11(1993)); Iuang etal. JVol/Microbiol Biotechnol 2(1): p.313-38 (2000), Additionalpt genes can be found in butyrate-producing bacterium L2-50 (Louis et aL. J.Bacteriol. 186:2099-2106 -253- (2004)) and Bacillus megaterium (Vazquez et al. Curr.Microbiol 42:345-349 (2001)). Additional exemplary phosphate-transferring acyltransferases include phosphotransacetylase, encoded bypta. The pta gene from E. coli encodes an enzyme that can convert acetyl-CoA into acetyl-phosphate, and vice versa (Suzuki, T. Biochim.BiophvsA cta 191:559-569 (1969)), This enzyme can also utilize propionyl-CoA instead of acetyl-CoA forming propionate in the process (Hesslinger et al. Mol Microbiol 27:477-492 (1998)). Information related to these proteins and genes is shown below. TABLE 61 Protein GenBituk ID GI number Organism Pta NP 416800.1 16130232 Escherichia coli Ptb NP_349676 15896327 Clostridium acetobuty/icumi Pth AAR19757.1 38425288 butyrate-producing bacterium L2-50 Ptb CAC07932.1 10046659 Bacillus megaterium [004911 Exemplary kinases include the E. coli acetate kinase, encoded by ackA (Skarstedt and Si Iverstein J. Biol. Chem. 251:6775-6783 (1976)), the C. acetobutylicum butyrate kinases, encoded by bukl and buk2 ((Walter et al. Gene 134(1):107-111 (1993); Huang et al. JVol Microbiol Biotechnol 2(1):33-38 (2000)), and the E. coli gamma-glutamyl kinase, encoded by proB (Smith et al. J.Bacteriol. 157:545-551 (1984)). These enzymes phosphorylate acetate, butyrate, and glutamate, respectively. The ackA gene product from E. coli also phosphorylates propionate (Hesslinger et al. Mollicrobiol 27:477-492 (1998)). Information related to these proteins and genes is shown below. TABLE 62 Protein GenBank I D GI number Organism AckA NP_416799,1 16130231 1scherichia coli Buk] NP 349675 15896326 Clostrilium acetobut'licum Buk2 Q9711 2013741 5 Clostridiman acetobutylicum -254- ProB NP 414777,1 16128228 Escherichia coli [004921 The hydrolysis of acetoacetyl-CoA or 3-hydroxybutyryl-CoA car alternatively be carried out by a single enzyme or enzyme complex that exhibits acetoacetyl-CoA or 3 hydroxybutyryl-CoA synthetase activity (steps Kand M, FIG. 4). This activity enables the net hydrolysis of the CoA-ester of either molecule, and in some cases, results in the simultaneous generation of ATP. For example, the product of the LSC] and LSCZ genes of S. cerevisiae and the sucC and sucD genes of E. coli naturally form a succinyl-CoA synthetase complex that catalyzes the formation of succinyl-CoA from succinate with the concomitant consumption of one ATP, a reaction which is reversible in vivo (Gruys et al., US Patent No. 5,958,745, filed September 28, 1999). Information related to these proteins and genes is shown below. TABLE 63 Protein GenBank ID G1 number Organism SucC NP 4152561 16128703 Escherichia coli SucD AAC73823.1 1786949 Escherichia coli LSCJ NP 014785 6324716 Saccharomnvces cerevisiae LSC2 NP011760 6321683 Saccharomvces cerevisiae [004931 Additional exemplary CoA-ligases include the rat dicarboxylate-CoA ligase for which the sequence is yet uncharacterized (Vaniecq et al., Biochemical f. 230:683-693 (1985)), either of the two characterized phenylacetate-CoA ligases from P. chrysogenum (Lamas-Maceiras et al., Biochem. J. 395:147-155 (2005): Wang et al, Biochen Biophy Res Coninua. 360(2):453-458 (2007)), the phenylacetate-CoA ligase from Pseuloinonaspwuida (Martinez-Blanco e al, J, Biol. Chen. 265:7084-7090 (1990)), and the 6-carboxyhexanoate-CoA ligase from Bacilis subtilis (Boweret al., J. Bacteriol. 178(14):4122-41.30 (1996)), Additional candidate enzymes are acetoacetyl-CoA synthetases from Mus inusculus (Hasegawa et al., Biochin. Biophys. Acta 1779:414-419 (2008)) and Hono sapiens (Ohgami et al., Biochenm. Pharnmacol. 65:989-994 (2003)), which naturally catalyze the ATP-dependant conversion of acetoacetate into acetoacetyl-CoA. 4-H ydroxybutyryl-CoA synthetase activity has been demonstrated in -2L55- Metallosphaera sedu/a (Berg et al., Science 318:1782-1786 (2007)). This function has been tentatively assigned to the Msed_1422 gene. Information related to these proteins and genes is shown below. TABLE 64 Protein GenBank ID GI number Organism Phil CAJ15517.1 77019264 Penicillium chriysogenum Ph/B- ABS 19624.1 152002983 Pe-nicilliun. chry-so genuin PaaF AAC24333.2 22711873 Pseudononas putida BioW N P 390902.2 50812281 Bacillus subtilis A CS NP_084486.1 21313520 Mus musculus AACS NP_076417.2 31982927 Hono sapiens Msed 1422 YP 001191504 146304188 Metallosphaera secula [004941 ADP-forming acetyl-CoA synthetase (ACD, EC 6.2.1.13) is another candidate enzyme that can couple the conversion of acyl-CoA esters to their corresponding acids with the concurrent synthesis of ATP (steps K and M, FIG. 4). Several enzymes with broad substrate specificities have been described in the literature. ACD I from Archaeoglobus.fidi/dus, encoded by AF 1211, was shown to operate on a variety of linear and branched-chain substrates including acetyl-CoA, propionyl-CoA, butyryl-CoA, acetate, propionate, butyrate, isobutyryate, isovalerate, succinate, fumarate, phenylacetate, indoleacetate (Musfeldt et al., J. Bacteriol. 184:636-644 (2002)), The enzyme from Haloarcula narisnortui (annotated as a. succinyl-CoA synthetase) accepts propionate, butyrate, and branched-chain acids (isovalerate and isobutyrate) as substrates, and was shown to operate in the forward and reverse directions (Brasen et a!. Arch. Microbiol. 182:277-287 (2004)). The ACD encoded by PAE3250 from hyperthermophilic crenarchaeon Pyrobaculun aerophilun showed the broadest substrate range of all characterized ACDs, reacting with acetyl-CoA, isobutyryl-CoA (preferred substrate) and phenylacetyl-CoA (Brasen iet al., supra (2004)). The enzymes from A. h/gidus, H. narisnortui and P. aerophihan have all been cloned, functionally expressed, and characterized in . coli (Musfeldt et al., supra; Brasen et al., supra (2004)). Information related to these proteins and genes is shown below. -256- TABLE 65 Protein GenBank ID GI number Organism Archaeoglobus fulgidus DSM AF1211 NP 070039.1 11498810 4304 Haloarcula inarismnortui A TC scs YP 135572. 1 55377722 43049 Pyrobaculumn erophilun sir. PAE3250 NP_560604.1 18313937 112 [004951 The conversion of 3-hydroxybutyrate to 3-hydroxybutyraldehyde can be carried out by a 3-hydroxybutyrate reductase (step N, FIG. 4). Similarly, the conversion of acetoacetate to acetoacetaldehyde can be carried out by an acetoacetate reductase (step L, FIG. 4). A suitable enzyme for these transformations is the aryl-aldehyde dehydrogenase, or equivalently a carboxylic acid reductase, from Nocardia iowensis. Carboxylic acid reductase catalyzes the magnesium, ATP and NADPH-dependent reduction of carboxylic acids to their corresponding aldehydes (Venkitasubramanian et al J. Biol. Chem. 282:478-485 (2007)). This enzyme, encoded by car, was cloned and functionally expressed in E. coli (Venkitasubramanian et al., . Biol. Chiem. 282:478-485 (2007)). Expression of the nyt gene product improved activity of the enzyme via post-transcriptional modification. The npt gene encodes a specific phosphopantetheine transferase (PPTase) that converts the inactive apo-enzyme to the active holo-enzyme. The natural substrate of this enzyme is vanillic acid, and the enzyme exhibits broad acceptance of aromatic and aliphatic substrates (Venkitasubramanian et al., in Biocatalysis in the Pharmaceutical and Biotechnology Industires, ed. R.N. Patel, Chapter 15, pp. 425-440, CRC Press LLC, Boca Raton, FL. (2006)). Information related to these proteins and genes is shown below. TABLE 66 Protein GenBank ID GI number Organism Car AAR91681.1 40796035 Nocardia iowensis (sp. NRRL 5646) Nut A1B183656.1 114848891 Nocardia iowensis (sp. NRRL 5646) -257- [00496] Additional car and npt genes can be identified based on sequence homology. TABLE 67 Protein GenBan k H) GI number Ortanism tdD9 - YP_978699.1 121638475____ fbteriwi bovis DCG DCC' 2812c Y1J 978898.1 121638674 V cobacteriwn boiS CG_ Nocari -a f-rcini-a IFM nfa20150 YP_118225.1 54023983 101 540213983 1015 2 Nocardia forcinica 1F M n/ia40540 YP 120266.1 "402601c4 -_ A4026024 10152 SGR_6790 YP 001 828302.1 Streptonces griseus subsp. I ------ 82-440583griseli sNBRC 13350 SGR_665 YP_0018221771 Streptomvces griseus subsp. 182434458 griseus NBRC 13350 MSMEG_2956 YP_887275.1 118473501 'obacterim smegmatis !VfC12 155 MSMEG_5739 YP 889972.1 118469671 Mvcobacterium smegnatis _ __ j 7 3 9C2 155 MSAIEG 2648 YP 886985.1 118471293 Mycobacteriumsmegmatis MC2 155 MAP1040c NP 959974.1 41407138 Mlcobacteritn aviun subsp. paratubercwiosis K-10 112899C NP_961833.1 41408997 Mvcobacterium avium subsp. paratuberculosis K-10 A4R_21 7 YP_001850422.1 183982131 V/ycobacterium imawinum M /MAR_296 YP_001851230.1 183982939 Mvwobacterium mariman Al ALVL4R 1916 YP 001850220.1 183981929 Vcobacteriwn marinum M IpauDRAFT 33060 ZP_04027864.1 227980601 T sukamurella paurometabola DSM/_ 20162 7pauDR A FT 20920 ZP_04026660.1 227979396 T ukaiurel/a pauromeltabola DSt 20162 CPCC7001 1320 ZP 05045 132.1 254431429 Cyanobin PCC7001 01 '7 D1)zI.Yostlt m ebiseoueunwi DDBDRAFT 0187729 XP 636931.1 66806417 ic [00497] An additional enzyme candidate found in Streptomyces griseus is encoded by the grjiC and griD genes. This enzyme is believed to convert 3-amino-4-hydroxybenzoic acid to 3-amino 4-hvdroxybenzaldehyde as deletion of either griC or griD led to accumulation of extracellular 3 acetylarnino-4-hydrox ybenzoic acid, a shunt product of 3-am ino-4-hydroxybenzoic acid -258metabolism (Suzuki, et al., J. Antibiot. 60(6):380-387 (2007)). Co-expression of griC and griD with SGR_665, an enzyme similar in sequence to the Nocardia lowensis npt, can be beneficial. Information related to these proteins and genes is shown below. T ABLE 68 Protein GenBank ID GI number Organism griC YP001825755.1 18238036 Strto cesgriseus subsp. griseus t Y --- 0018575.1 124-3036NBRC 13350 grid YP_001825756.1 182438037 treptomyces griseus subsp. griseus NBRC 13350 [00498] An enzyme with similar characteristics, alpha-aminoadipate reductase (AAR, EC 1.2.1.31), participates in lysine biosynthesis pathways in some fungal species. This enzyme naturally reduces alpha-aminoadipate to alpha-aminoadipate semialdehyde. The carboxyl group is first activated through the ATP-dependent formation of an adenylate that is then reduced by NAD(P)H to yield the aldehyde and AMP. Like CAR, this enzyme utilizes magnesium and requires activation by a PPTase. Enzyme candidates for AAR and its corresponding PPTase are found in SaccharomVces cerevisiae (Morris et al., Gene 98:141-145 (1991)), Candida albicans (Guo et al., Mol. Genet. Genonies 269:271 -279 (2003)), and Schizosaccharomyces pombe (Ford et al., Curr. Genet. 28:131-137 (1995)). The AAR from S. pombe exhibited significant activity when expressed in E. coli (Guo et al., Yeast 21:1279-1288 (2004)). The AAR from Penicilliun chrysogenum accepts S-carboxymethyl-L-cysteine as an alternate substrate, but did not react with adipate, L-glutamate or diaminopimelate (Hijarrubia et al., J. Biol. Chem. 278:8250-8256 (2003)). The gene encoding the I. chrysogenun PPTase has not been identified to date. Information related to these proteins and genes is shown below. TABLE 69 Protein GenBank ID GI number Organism L YS2 AAA34747.1 171867 Saccharonvces cerevisiae L YS.5 P50113.1 1708896 Saccharomvces cerevisiae -259- L YS2 A AC02241.1 2853226 Candida albicans LYS5 AA026020.1 28136195 Candtida albicans 1yslp P40976.3 13124791 Schizosaccharomyces ponbe Lys7p Q10474.1 1723561 Schizosaccharonyces pombe --------- ---------------------------------------------------------------------------------------------------------------------- Lvs2 CAA74300J1 3282044 Penicilliun chrysogenunm [004991 Any of these CAR or CAR-like enzymes can exhibit 3-hydroxybutyrate or acetoacetate reductase activity or can be engineered to do so. 1005001 Alternatively, the acetoacetyl-CoA depicted in the 1 .3-3DO pathway(s) of FIG. 4 can be synthesized from acetyl-CoA and malonyl-CoA by acetoacetyl-CoA synthase, for example, as depicted in FIG. 7 (steps E and F) or FIG. 9, wherein acetyl-CoA is converted to malonyl-CoA by acetyl-CoA carboxylase, and acetoacetyl-CoA is synthesized from acetyl-CoA and malonyl CoA by acetoacetyl-CoA synthase. [005011 Acetoacetyl-CoA can also be synthesized from acetyl-CoA and malonyl-CoA by acetoacetyl-CoA synthase (EC 2.3.1.194). This enzyme (FhsA) has been characterized in the soil bacterium Streptonzyces sp. CL190 where it participates in mevalonate biosynthesis (Okamura et al, PAS USA 107:11265-70 (2010)). As this enzyme catalyzes an essentially irreversible reaction, it is particularly useful for metabolic engineering applications for overproducing metabolites, fuels or chemicals derived from acetoacetyl-CoA. For example, the enzyme has been heterologously expressed in organisms that biosynthesize butanol (Lan et al, PNAS USA (2012)) and poly-(3-hydroxybutyrate) (Matsumoto et al, Biosci Biotech Biochem, 75:364-366 (2011). Other relevant products of interest include 1,4-butanediol and isopropanol. Other acetoacetyl-CoA synthase genes can be identified by sequence homology tojhsA. TABLE 70 Protein GenBank ID GI Number Organism BAJ 83474.1 325302227 Streptomyces sp ___ ___ __ ___ ___ __ __ ___ __ ___ ___ __ _ _ ___ __ ___ ___ __ CL 190 AB183750.1:1]991..12971 BAD86806.1 577 53876 Streptomyces sp. KO-3988 -260epzT ADQ43379.1 312190954 Streptomyces cinnamionensis ppzT CAX48662. 1 238623523 Strcpton"'ces anidatus 031 22085 ZP_09840373.1 378817444 Nocardia brasiliensis EXAMPLE V

INSER

T

ION OF NUCL EIC ACID SEQUENCES AND GENES IN £ CEREVISME 1005021 This Example describes methods for the insertion of nucleic acid sequences into S. cerevisiae. Increased production of cytosolic acetyl-CoA can be accomplished by inserting nucleic acid sequences encoding genes described in Example 1. Conversion of cytosolic acetyl CoA to 1,3-BDO can be accomplished by inserting nucleic acid sequences encoding genes described in Example I. 1005031 Nucleic acid sequences and genes can be inserted into and expressed in S. cerevisiae using several methods. Some insertion methods are plasmid-based, whereas others allow for the incorporation of the gene into the chromosome (Guthrie and Fink, Guide to Yeast Genetics and Molecular and Cell Biology, Part B,Volume 350, Academic Press (2002); Guthrie and Fink, Guide to Yeast Genetics and Molecular and Celi Biology, Par; C, Volume 351, Academic Press (2002)). High copy number plasmids using auxotrophic (e.g., URA3, TRP 1, HIS3, LEU2) or antibiotic selectable markers (e.g., ZeoR or KanR) can be used, often with strong, constitutive promoters such as PGK1 or ACTI and a transcription terminator-polyadenylation region such as those from CYCI or AOX. Many examples are available, including pVV214 (a 2 micron plasmid with URA3 selectable marker) and pVV200 (2 micron plasmid with TlRP selectable marker) (Van et al., Yeast 20:739-746 (2003)). Alternatively, relatively low copy plasmids can be used, including pRS313 and pRS315 (Si korski and [Hieter, Genetics 122:19-27 (1989) both of which require that a promoter (e.g., PGK1 or ACTI) and a terminator (e.g., CYC 1, AOX) are added. -261- [005041 The integration of genes into the chromosome requires an integrative promoter-based expression vector, for example, a construct that includes a promoter, the gene of interest, a terminator, and a selectable marker with a promoter, flanked by FRT sites, loxPl sites, or direct repeats enabling the removal and recycling of the resistance marker. The method entails the synthesis and amplification of the gene of interest with suitable primers, followed by the digestion of the gene at a unique restriction site, such as that created by the EcoRI and XhoI enzymes (Vellanki et al., Biotechnol Lett. 29:313-318 (2007)). The gene of interest is inserted at the EcoRI and Xhol sites into a suitable expression vector, downstream of the promoter. The gene insertion is verified by PCR and DNA sequence analysis. The recombinant plasmid is then linearized and integrated at a desired site into the chromosomal DNA of S. cerevisiae using an appropriate transformation method. The cells are plated on the YPD medium with the appropriate selection marker (e.g., kanamycin) and incubated for 2-3 days. The transformants are analyzed for the requisite gene insert by colony PCR. [005051 To remove the antibiotic marker from a construct flanked by loxP sites, a plasmid containing the CrC recombinase is introduced. Cre recombinase promotes the excision of sequences flanked by loxP sites. (Gueldener et al., ATucleic Acids Res. 30:e23 (2002)). The resulting strain is cured of the Cre plasmid by successive culturing on media without any antibiotic present. The final strain has a markerless gene deletion, and thus the same method can be used to introduce multiple insertions in the same strain. Alternatively, the FLP-FRT system can be used in an analogous manner. This system involves the recombination of sequences between short Flipase Recognition Target (FRT) sites by the Flipase recombination enzyme (FLP) derived from the 2pg plasmid of the yeast Saccharomyces cerevisiae (Sadowski, P. D., Prog.Nucleic.Acid.Res.fol. Biol. 51:53-91 (1995); Zhu and Sadowski J.Biol.(Iem. 270:23044 23054 (1995)). Similarly, gene deletion methodologies can be carried out as described in refs, Baudin et al., Nucleic.Acids Res. 21:3329-3330 (1993); Brachmann et al., Yeast 14:115-132 (1998); Giaever et al., Nature 418:387-391 (2002); Longtine et al., Yeast 14:953-961 (1998) Winzeler et al., Science 285:901-906 (1999). -262- EXAMPLE VI INSERTION OF NUCLEIC ACID SEQUENCES AND GENES IN S CEREVISL4E [005061 This Example describes the insertion of genes into S. cerevisiae for the production of 1,3-BDO. [005071 Strain construction: Saccharonces cerevisiae hap] oi d strain BY4741 (MA Ta his3A I leu2AO metl5AO ura3AO) with pdc5 replaced with the Kanamycin resistance gene, pdc5::kanr (clone ID 4091) from the Saccharoinyces Genome Deletion Project can be further manipulated by a double crossover event using homologous recombination to replace the TRPI gene with URA3. The resulting strain can be grown on 5-FOA plates to "URA blast" the strain, thereby selecting for clones that had ura3 mutations. A clone from this plate can be expanded.The strain with the final genotype BY4741 (MATa his3Al leu2A0 met15AO ura3AO trpl::ura3 pdc5::kanr) can be used for 1,3-BDO heterologous pathway expression. The strain can be grown on synthetic defined media which contains Yeast Nitrogen Base (.7g/L), annonium sulfate (5g/L) and a complete supplement mixture (CSM) of amino acids minus -His, -Leu, -Trp, -Ura, dextrose can also be added (Sunrise Science Products, Inc. San Diego, CA catalog #1788-100). An appropriate carbon source is either 0.2% glucose or 0.2% sucrose plus 2% galactose. [005081 To construct the 1,3-BDO pathway in S. cerevisiae, genes can be identified, cloned, sequenced and expressed from expression veciors. Genes and accession numbers are described in Example I. 1,3-BDO pathway genes can be cloned into pESC vectors pESC-HIS, pESC-LEU. pESC-TRP, and pESC-URA (Stratagene, cat #217455). These are shuttle vectors that can replicate in either E. coli or S. cerevisiae. They have dual galactose (GAL1, GAL10) divergent promoters that are inhibited in the presence of dextrose (glucose) but provide inducible expression in the presence of galactose sugar. The acetoacetyl-CoA thiolase and acetoacetyl CoA reductase can be cloned into pESC-His; 3-hydroxybutyryl-CoA reductase and 3 hydroxybutyraldehyde reductase can be cloned into pESC-Leu, and pyruvate formate lyases subunits A and B can be cloned into pESC-Ura. [005091 All enzyme assays can be performed from cells which had first expressed the appropriate gene(s). Cells can be spun down, lysed in a bead beater with glass beads, and cell debris removed by centrifugation to generate crude extracts. -263- [005101 Substrate can be added to cell extracts and assayed for activity. Acetoacetyl-CoA thiolase activity can be determined by adding acetyl-CoA to extracts. If the reaction condensed the acetyl-CoA components, free CoA-SH will be released. The free CoA-SH fonns a complex with DTNB to forrn DTNB-CoA, which can be detected by absorbance at 410 nm. To assay acetoacetyl-CoA reductase activity, acetoacetyl-CoA and NADH can be added to extracts. Acetoacetaty-CoA absorbs at 304 nm and its decrease is used to monitor conversion of acetoacetyl-CoA to 3-hydroxybutyryl-CoA. 3-Hydroxybutyryl-CoA reductase and 3 hydroxybutyraldehyde reductase can be assayed by adding the appropriate substrate along with NADH to cell extracts. Decrease of NA DH can then be assayed by fluorescence since NADH absorbs light with wavelength of 340 nm and radiates secondary (fluorescence) photons with a wavelength of 450 nm. [005111 To detect pyruvate formate lyase activity in yeast, cells, extracts and reagents can be prepared anaerobically as the enzyme is known to be inhibited by oxygen. Because the DTNB CoA reaction is inhibited by reducing agents required for the preparation of anaerobic extracts, assaying for the release of CoA-SH with DNTB can not be performed. Therefore, the product of the reaction (Acetyl-CoA) can be directly analyzed by mass spectrometry when extracts are provided with pyruvate. [005121 Yeast cultures can be inoculated into synthetic defined media without His, Leu, Trp, Ura. Samples from 1,3-BDO production cultures can be collected by removing a majority of cells by centrifugation at 1 7,000 rpm for five minutes at room temperature in a microcentrifuge. Supernatants can be filtered through a 0.22 pm filter to remove trace amounts of cells and can be used directly for analysis by GC-MS. [005131 The engineered strains will be characterized by measuring the growth rate, the substrate uptake rate, and the product/byproduct secretion rate. Cultures will be grown overnight and used as inoculum for a fresh batch culture for which measurements are taken during exponential growth. The growth rate can be determined by measuring optical density using a spectrophotom eter (A600). Concentrations of glucose, 1,3-13DO, alcohols, and other organic acid byproducts in the culture supernatant can be determined by analytical methods including HPLC using an HPX-871 column (BioRad), or GC-MS, and used to calculate uptake and -264secretion rates. Cultures can then bebrought to steady state exponential growth via sub-culturing for enzyme assays. All experiments wiII be performed with triplicate cultures. EXAMPLE VII UTI LIZATION OF PATHWAY ENZYMES WITH A PRE FERENCE FOR NA DH [005141 The production of acetyl-CoA from glucose can generate at most fo)ur reducing equivalents in the form of NADH. A straightforward and energy efficient mode of maximizing the yield of reducing equivalents is to employ the Embden-Meyerhof-Pamas glycolysis pathway (EMP pathway). I n many carbohydrate utilizing organisms, one NA Di molecule is generated per oxidation of each glyceraldehyde-3 -phosphate molecule by means of glyceraldehyde-3 phosphate dehydrogenase. Given that two molecules of glyceral deh yde-3 -phosphate are generated per molecule of glucose metabolized via the EMP pathway, two NADH molecules can be obtained from the conversion of glucose to pyruvate. [005151 Two additional molecules of NADH can be generated from conversion of pyruvate to acetyl-CoA given that two molecules of pyruvate are generated per molecule of glucose metabolized via the EMP pathway. This would require employing any of the following enzymes or enzyme sets to convert pyruvate to acetyl-CoA: 1) NAD-dependant pyruvate dehydrogenase; 2) Pyruvate formate lyase and NAD-dependant formate dehydrogenase; 3) Pyruvate:ferredoxin oxidoreductase and NADH:ferredoxin oxidoreductase; 4) Pyruvate decarboxylase and an NAD-dependant acylating acetylaldehyde dehydrogenase; 5') Pyruvate decarboxylase, NAD-dependant acylating acetaldehyde dehydrogenase, acetate kinase, and phosphotransacetylase; and 6) Pyruvate decarboxylase, NAD-dependant acylating acetaldehyde dehydrogen ase, and acetyl-CoA synthetase. 1005161 Overall, four molecules of NADHI can be attained per glucose molecule metabolized. The 1,3-BDO pathway requires three reduction steps from acetyl-CoA. Therefore, it can be -L265possible that each of these three reduction steps will utilize NADPH or NADH as the reducing agents, in turn converting these molecules to NA DP or NAD, respectively. Therefore, it is desireable that all reduction steps are NADH-dependant in order to maximize the yield of 1,3 BDO. High yields of 1,3-BDO can thus be accomplished by: 1) Identifying and implementing endogenous or exogenous 1,3-BDO pathway enzymes with a stronger preference for NADH than other reducing equivalents such as NADPH, 2) Attenuating one or more endogenous 1,3-BDO pathway enzymes that contribute NADPH-dependant reduction activity, 3) Altering the cofactor specificity of endogenous or exogenous I,3-BDO pathway enzymes so that they have a stronger preference for NADH than their natural versions, or 4) Altering the cofactor specificity of endogenous or exogenous 1,3-BDO pathway enzymes so that they have a weaker preference for NADPH than their natural versions. [005171 The individual enzyme or protein activities from the endogenous or exogenous DNA sequences can be assayed using methods well known in the art. For example, the genes can be expressed in E. coli and the activity of their encoded proteins can be measured using cell extracts as described in Example V. Alternatively, the enzymes can be purified using standard procedures well known in the art and assayed for activity. Spectrophotometric based assays are particularly effective. [005181 Several examples and methods of altering the cofactor specificity of enzymes are known in the art. For example, Khoury et al. (Protein Sci. 2009 October; 18(10): 2125-2138) created several xylose reductase enzymes with an increased affinity for NADH and decreased affinity for NADP-. Ehsani et al (Biotechnology and Bioengineering, Volume 104, Issue 2, pages 381-389, 1 October 2009) drastically decreased activity of 2,3-butanediol dehydrogenase on NA DI while increasing activity on NADPH. Machielsen et al (Engineering in Life Sciences, Volume 9, Issue 1, pages 38-44, February 2009) dramatically increased activity of alcohol dehydrogenase on NADH. Khoury et al (Protein Sci. 2009 October; 18(10): 2125-2138) list in -266- Table I several previous examples of successfully changing the cofactor preference of over 25 other enzymes. Additional descriptions can be found in Lutz et al, Protein Engineering Handbook, Volume 1 and Volume 2, 2009, Wiley-VCH Verlag GmbH & Co. KGaA, in particular, Chapter 3 1: Altering Enzyme Substrate and Cofactor Specificity via Protein Engineering. EXAMPLE ViIl: DETERMINING COFACTOR PREFERENCE OF PATHWAY ENZYMES [00519] This example describes an experimental method for determining the cofactor preference of an enzyme. [005201 Cofactor preference of enzymes for each of the pathway steps are determined by cloning the individual genes on a plasmid behind a constitutive or inducible promoter and transforming into a host organism such as Escherichia coli. For example, genes encoding enzymes that catalyze pathway steps from: 1) acetoacetyl-CoA to 3-hydroxybutyryl-CoA, 2) 3 hydroxybutyryl-CoA to 3-hydroxybutyraldehyde, 3) 3-hydroxybutyraldehyde to 1,3-butanediol, or 4) 3-hydroxybutyrate to 3-hydroxybutyraldehyde can be assembled onto the pZ-based expression vectors as described below. [005211] Replacement of the Stuffer Fragment in the pZ-based Expression Vectors. Vector backbones were obtained from Dr. Rolf Lutz of Expressys (http://www.expressys.de/). The vectors and strains are based on the pZ Expression System developed by Lutz and Bujard (Nucleic Acis Res 25, 1203-1210 (1997)). The pZE13luc, pZA33luc, pZS*131uc and pZE22luc contain the luciferase gene as a stuffer fragment. To replace the luciferase stuffer fragment with a lacZ-alpha fragment flanked by appropriate restriction enzyme sites, the luciferase stuffer fragment is removed from each vector by digestion with EcoRl and Xbal. The lacZ-alpha fragment is PCR amplified from pUC19 with the following primers: lacZalpha-RI 5 'GACGAATTCGCTAGCAAGAGGAGAAGTCGACATGTCCAATTCACTGGCCGTCGTT TTAC3' (SEQ ID NO: 1) lacZalpha 3'BB -267- 5'-GACCCTAGGAAGCTTTCTAGAGTCGACCTATGCGGCATCAGAGCAGA-3' (SEQ ID NO: 2) [005221 This generates a fragment with a 5' end of EcoRI site, Nhel site, a Ribosornal Binding Site, a SalI site and the start codon. On the 3' end of the fragment are the stop codon, XbaL, Hindl, and Avr]I sites. The PCR product is digested with EcoRI and AvrII and ligated into the base vectors digested with EcoRI and Xbal (Xbal and AvrlI have compatible ends and generate a non-site). Because NheI and Xbal restriction enzyme sites generate compatible ends that can be ligated together (but generate a site after ligation that is not digested by either enzyme), the genes cloned into the vectors can be "Biobricked" together (http :/open wetware.org/wiki/Synthetic Biology: Bio Bricks). Briefly, this method enables joining an unlimited number of genes into the vector using the same 2 restriction sites (as long as the sites do not appear internal to the genes), because the sites between the genes are destroyed after each addition. These vectors can be subsequently modified using the Phusion@ Site Directed Mutagenesis Kit (NEB, Ipswich, MA, USA) to insert the spacer sequence AATTAA between the EcoRI and Nhel sites. This eliminates a putative stem loop structure in the RNA that bound the RBS and start codon. [005231 All vectors have the pZ designation followed by letters and numbers indicating the origin of replication, antibiotic resistance marker and promoter/regulatory unit. The origin of replication is the second letter and is denoted by E for ColE1I, A for p15A and S for pSC101 (as well as a lower copy number version of pSClO1 designated S*) - based origins. The first number represents the antibiotic resistance marker (1 for Ampicillin, 2 for Kanamycin, 3 for Chloramphenicol). The final number defines the promoter that regulated the gene of interest (1 for PLtetO-1, 2 for PLlacO-1 and 3 for PAIlacO-1). For the work discussed here we employed three base vectors, pZS*13S, pZA33S and pZE13S. modified for the biobricks insertions as discussed above. [00524] Plasnids containing genes encoding pathway enzymes can then transformed into host strains containing laciQ, which allow inducible expression by addition of isopropyl J3-Dthiogalactopyranoside (IPTG). Activities of the heterologous enzymes are tested in in vitro assays, using strain E. coli MG1655 laclQ as the host for the plasmid constructs containing the -268pathway genes. Cells can be grown aerobically in LB media (Difco) containing the appropriate antibiotics for each construct, and induced by addition of I PTG at 1 mM when the optical density (OD600) reached approximately 0.5. Cells can be harvested after 6 hours, and enzyme assays conducted as discussed below. [005251 In Vitro Enw;ne Assays. To obtain crude extracts for activity assays, cells can be harvested by centrifugation at 4,500 rpm (Beckman-Coulter, Allegera X-15R) for 10 min. The pellets are resuspended in 0.3 mL BugBuster (Novagen) reagent with benzonase and lysozyme, and lysis proceeds for about 15 minutes at room temperature with gentle shaking. Cell-free lysate is obtained by centrifugation at 14,000 rpm (Eppendorf centrifuge 5402) for 30 min at 4'C. Cell protein in the sample is determined using the method of Bradford et al., Anal. Biochem. 72:248-254 (1976), and specific enzyme assays conducted as described below. Activities are reported in Units/mg protein, where a unit of activity is defined as the amount of enzyme required to convert I micromol of substrate in -1 minute at room temperature. [005261 Pathway steps can be assayed in the reductive direction using a procedure adapted from several literature sources (Durre et al.. FEMS Microbiol. Rev. 17:251-262 (1995); Palosaari and Rogers, Bacteriol. 170:2971-2976 (1988) and Welch et al., Arch, Biochem. Biophys. 273:309-318 (1989). The oxidation of NADH or NADPH can be followed by reading absorbance at 340 nM every four seconds for a total of 240 seconds at room temperature. The reductive assays can be performed in 100 mM MOPS (adjusted to pH 7.5 with KOH), 0.4 mM NADI or 0.4 mM NADPH, and from 1 to 50 umol of cell extract, For carboxylic acid reductase-like enzymes, ATP can also be added at saturating concentrations. The reaction can be started by adding the following reagents: 100 pmol of 100 mM acetoacetyl-CoA, 3 hydroxybutyryl-CoA, 3 -hydroxybutyrate, or 3-hydroxybutyraldehyde. The spectrophotometer is quickly blanked and then the kinetic read is started. The resulting slope of the reduction in absorbance at 340 nM/I per minute, along with the molar extinction coefficient of NAD(P)FI at 340 nM (6000) and the protein concentration of the extract, can be used to determine the specific activity. -269- EXAMPLE IX METHODS FOR INCREASING NADPI AVAILABILITY [005271 In some cases, it can be advantageous to employ pathway enzymes that have activity using NADPH as the reducing agent. For example, N-ADPI-dependant pathway enzymes can be highly specific for pathway intermediates such as acetoacetyl-CoA, 3-hydroxybutyryl-CoA, 3 hydroxybutyrate, or 3-hydroxybutyraIdehyde or can possess favorable kinetic properties using NADPH as a substrate. If one or more pathway steps is INADPH dependant, several alternative approaches to increase NADPH availability can be employed. These include: 1) Increasing flux relative to wild-type through the oxidative branch of the pentose phosphate pathway comprising gl ucose-6-phosphate dehydrogenase, 6 phosphogluconolactonase, and 6-phosphogluconate dehydrogenase (decarboxylating). This will generate 2 NADPH molecules per glucose-6 phosphate metabolized. However, the decarboxylation step will reduce the maximum theoretical yield of I,3-butanediol. 2) Increasing flux relative to wild-type through the Entner Doudoroff pathway comprising glucose-6-phosphate dehydrogenase, 6-phosphogluconolactonase, phosphogluconate dehydratase, and 2-keto-3-deoxygluconate 6-phosphate aldolase. 3) Introducing a soluble transhydrogenase to convert NAD[I to NADPH. 4) Introducing a membrane-bound transhydrogenase to convert NADH to NADPH. 5) Employing an NADP-dependant glyceraldehyde-3-phosph-ate dehydrogenase. 6) Employing any of the following enzymes or enzyme sets to convert pyruvate to acetyl-CoA a) NADP-dependant pynvate dehydrogenase; b) Pyruvate formate Ivase and NADP-dependant formate dehydrogenase; c) Pyruvate:ferredoxin oxidoreductase and NADP l: ferredoxin oxidoreductase; d) Pynvate decarboxylase and an NADP-dependant acylating acetylaldehyde dehydrogenase; -270e) Pyruvate decarboxylase, NADP-dependant acetaldehyde dehydrogenase, acetate kinase, and phosphotransacetylase; and 0 Pyruvate decarboxylase, NADP-dependant acetaldehyde dehydrogenase,and acetyl-CoA synthetase; and optionally attenuating NAD-dependant versions of these enzymes. 7) Altering the cofactor specificity of a native glyceraldehyde-3-phosphate dehydrogenase, pynivate dehydrogenase, formate dehydrogenase, or acylating acetylaidehyde dehydrogenase to have a stronger preference for NADPH than their natural versions. 8) Altering the cofactor specificity of a native glyceraldehyde-3-phosphate dehydrogenase, pyruvate dehydrogenase, formate dehydrogenase, or acylating acetylaldehyde dehydrogenase to have a weaker preference for NADH than their natural versions. [005281 The individual enzyme or protein activities from the endogenous or exogenous DNA sequences can be assayed using methods well known in the art. For example, the genes can be expressed in E. coli and the activity of their encoded proteins can be measured using cell extracts as described in the previous example. Alternatively, the enzymes can be purified using standard procedures well known in the art and assayed for activity. Spectrophotometric based assays are particularly effective. [005291 Several examples and methods of altering the cofactor specificity of enzymes are known in the art For exarnple, Khoury et al (Protein Sci. 2009 October; 18(10): 2125-2138) created several xylose reductase enzymes with an increased affinity for NADH and decreased affinity for NA DPH. Ehsani et al (Biotechnology and Bioengineering, Volume 104, Issue 2, pages 381-389, 1 October 2009) drastically decreased activity of 2,3-butanediol dehydrogenase on NADH while increasing activity on NADPH. Machielsen et al (Engineering in Life Sciences, Volume 9, Issue 1, pages 38-44, February 2009) dramatically increased activity of alcohol dehydrogenase on NADH. Khoury et al (Protein Sc. 2009 October; 18(10): 2125-2 138) list in Table I several previous examples of successfully changing the cofactor preference of over 25 other enzymes. Additional descriptions can be found in Lutz et al, Protein Engineering Handbook, Volume 1 and Volume 2, 2009, Wiley-VCH Verlag GmbH & Co. KGaA, in -271particular, Chapter 31: Altering Enzyme Substrate and Cofactor Specificity via Protein Engineer ng. [00530] Enzyme candidates for these steps are provided below. TABLE 70 Glucose-6-ph osp hate dehydrogenase Protein GenBank ID GI N umber Organism ZWF1 NP_014158.1 6324088 Saccharomyces cerevisiae S288c ZWFI XP 504275.1 50553728 Yarrowa bpolytica Zwf XP 002548953.1 255728055 Candida trnuop is MTA-3404 Zwf XP_001400342.1 145233939 Aspergillus niger CBS 513.88 KLLA0D19855g XP 453944.1 50307901 Kluyveronyces lactis NRRL Y-1140 TABLE 71 6-Phosphogluconolactonase Protein GenBank ID G] Number Organism SOL3 NP_012033.2 82795254 Saccharonces cerev'sfae S288c SOL4 NP 0117641 6321687 Saccharonces cerev'sfae S288c YAL1OEl1671g XP 5038301 50552840 Yarrowla lipolytica YALIOC19085 g XP_501998.1 50549055 Yarrowia lipolytica ANI 1 656014 XP_001388941.1 145229265 Aspergius nier CBS 513.88 CTG -- 00665 XP -- 0 012 54 58 84. 1 2 5572118 99 C'andida tropicaiis -1M4404I CTRG_02095 XP_002547788.1 255725718 Candida tropicalis MYA-3404 KLLAOA05390g XP_451238.1 50302605 Kluvecromyces facts NRRL Y-i140 KLLAOC08415g XP452574.1 50305231 Kluvveromyices factis NRRL Y-1 140 -272- TABLE 72 6-Phosphodguconate dehydrogenase (decarboxvlating) Protein GenBank ID GI Number Organism GNDI NP 012053.1 6321977 Saccharonyces cerevisiae S288c GND2 NP 011772.1 6321695 Saccharonyces cerevisiae S288c ANT_1_282094 XP_001394208.2 317032184 Aspergillus nigger CBS 513.88 ANI_2126094 XP_001394596.2 317032939 Aspergillus niger CBS 513.88 YALIOB15598g XP_500938.1 50546937 Yarrowia lipolytica CTRG_03660 XP_002549363.1 255728875 Candida tropicalis MYA-3404 KLLA0A09339g XP_451408.1 50302941 Kluyveromyces lactis NRR L Y-1140 TABLE 73 Phosphogluconate dehvdratase Protein GenBank ID GI Number Organism Edd AAC74921.1 1788157 Eseherichia coli K-12. M01655 Edd AAG29866.1 11095426 Zymomonas mobilis subsp. mobilis ZM4 Edd YP_350103. 1 77460596 Pseudomonas fluorescens Pf0-i ANTI_12126094 XP_001394596.2 317032939 Aspergillus niger CBS 5 13.88 YA LIOB 1I5598g XP_500938.1 50546937 Yarrowia lipolytica CTRG_03660 XP_002549363-1 255728875 Candida tropicalis MYA-3404 KLLA0A09339g XP_451408.1 50302941 Kluyveromyces lactis NRRL Y- 1140 TABLE 74 2-Keto-3-deoxvgluconate 6-phosphate aldolase Protein GenBank ID GI Number Organism Eda NP_416364.1 16129803 Escherichia coli K-12 MG1655 Eda Q00384.2 59802878 Zymomonas mobilis subsp. mobilis ZM4 Eda ABA76098.1 77384585 Pseudomonas fluorescens Pf0-i -273- TABLE 75 Soluble transhvdrogenase Protein GenBank ID GI Number Organism StIA NP 418397.2 90111670 Escherichia coli K-12 MG1655 StIBA YP 0 027(.19 86 58. 1 22694-3585 Azotobacter vinclaudji DJ SthA 005139.3 11135075 Pseudomonas fluorescens TABLE 76 Membrane-bound transhydrogenase Protein GenBank ID GI Number Organism ANI 1 29100 XP 001400109.2 317027842 Aspergillus niger CBS 513.88 Pc2 1 g18800 XP 002568871.1 226943585 255956237 Penicillium cbrysogenm Wisconsin 54-1255 SthA 005 139.3 11135075 Pseudomonas fluorescens NCU01 140 XP 961047.2 164426165 Neurospora crassa OR74A TABLE 77 NADP-dependantI Tveeraldehlde-3- hosphate dehydrogenase Protein GenBank ID GI Number Organism gapN AAA9 1091.1 642667 Streptococcus mutans NP-GAPDH AEC075 55.1 330 2 52461 Arabidopsis thaliana GAPN AAM776 79.2 82469904 Triticum aestivum gapN CA156300. 1 87298962 Clostridium acetobutylicum INADP-GAPDH 2D2I_A 112490271 Synechococcus clongatus PCC 7942 NADP-GAPDI- CAA62619.1 4741714 Synechococcus elongatus PCC 7942 GDPi XP_455496.1 50310947 Kluyveronyces lactis NRRL Y-1 140 HP 1346 NP 208138.1 15645959 [Helicobacter pylori 26695 TABLE 78 NAD-dependant gIlceraldehyde-3-phosphate dehvdrogenase Protein GenBank ID GI Number Organism ------------------------------------ ---------------------------- --------------------------------------------------------------------------- TDH1 NP 012483.1 6322409 Saccharomyces cerevisiae s288c TDH2 NP 012542.1 6322468 Saccharomyces cerevisiaes288c TD-3 NP_011708.1 632163 Saccharomyces cerevisiae s288c KLLAOA11858g XP 451516.1 50303157 Kluyveromyces lactis NRRL Y-1140 KLLAOF20988g XP_4560221 50311981 Kluyveromyces lactis NRRL Y-1140 ANI11256144 XP_001397496.1 145251966 Aspergillus niger CBS 513.88 YAL10C06369g XP_501515.1 50548091 Yarrowia lipolytica CTRG_05666 NP_002551368,1 255732890 Candida tropicalis MYA-3404 TABLE 79 NADP-dependant pyruvate dehydrogenase Protein GenBank ID GI Number Organism PNO Q941N5.1 33112418 Euglena gracilis cgd4_690 XP_625673.1 66356990 Cryptosporidium parvum Iowa II TPP PFOR PNO NP_002765111.11 294867463 Perkinsus marinus ATCC 50983 aceE NP_414656.1 50303157 Escherichia coli K-12 MG1655 aceF NP_414657.1 6128108 Escherichia coli K-12 MG1655 [005311 Mutated LpdA from E. coli K- 12 MG1655 described in Biochemistry, 1993, 32 (11), pp 2737-2740: MS T E IK'T'QVVVLGAGPAGY SAAFRCADLGLETVIVE RYNTLGGVCLNVGCI PSKALLHVAKVIE EAKALAEHG IVFGE PKTDI DK TRTWKEKVINQL T GGLAGMAKGRKVKVVNGLGKFTGANTLEVE GENGK TVINFDNAIIAAGSR IQL PFIPHEDPR IWDS TDALELKEVPERLLVMGGGIIGLEMG T VYHALOSQI DVVVRKHQV I RAADKD IVKVF TKR I SKKFNLMLETKVTAVEAKEDGIYVTMECKK APAEPQRYDAVLVA IGRVPNGKN L DAGKAGVEVDDRGF I RVDKQLRTNVPH I FA IGDIVGQPML, -25- AHKGVHJE GEVAAEV I ACGKKHIY FDCPKV PS I AY T E PEVAWVGLTEKEAKE KG I S YE T AT F PVIAAS GRAIASDCADGMITKL.IFDK ES HRVIGGAIVGTNGELLGEIGLAIEMGCDAEDIALTII IAHPTL FE SVGLAAEVFECGS I T DL PNPKAKKK (SEQ ID NO:3) [005321 Mutated LpdA from E. coli K-12 MG1655 described in Biochemistry, 1993,32 (11), pp 2737---2740: MS T E lK T QVVVLGAC PAGY S AAFRCADLGLETVI VEPRYN TLC GGCLNVCI PSKALLHVAKVI E EAKAL AE HG IVFGE PK T DI DK I RTWKEKV INQL T GCL ACMAKGRKVKVVNGL GKFT GANT L EVE GENRK TVINFDNAI IAAGSR P I QL PFI PHEDPRIWDS TDAL E LKEVPERLLVG i IALEMAT VY KALGSQ I DVVVRKI-IQV I RAADKD IVKVF T KR I S KKFN LMLE TKV EN/rAVEAKE DC I YV'TlME GKK AP AE PQRY DAVL VA IGRPNGKNL DAGKAGVE VD RG F I VDKQLR T N VPH I FA IGD IVGQ PML A.HKGVHECG HVAAEVi AGKKH.YFDPKVi P S IAY T E PEVAWVGLTEKEAKEKGIS YETAT F PWAAS GRA IAS DCADGMTKL I FDKE S HRCViGA IVG TNGE LLE I GLA I EMGCDAEDIALT I LALPTL HE SVGLAAEVFE GS IT DL PNPKAKKK (S EQ ID NO:4) TABLE 80 NADP-denendant formate dehydrogenase Protein GenBank ID GI Number Organism fd h ACF3 5003. '194220249 Burkholderia stabilis fdh ABC20599.2 | 146386149 Moorella thermoacetica ATCC 39073 [00533] Mutant Canclcia bodinii enzyme described in Journal of Molecular Catalysis B: Enzymatic, Volume 61, Issues 3-4, December 2009, Pages 157-161: MK I VLVLY DAGKLAADEEKLYVG CTENKL GIANWLKDCHLITTSDKEGE T TSDKECE TSELDKL I P TDAD I IT T PFH PAY I TKERL DKANLKLVAGVSDI DLDY I NOTG KK I SVLEVTGSNVVSVAE11VV MTMLVLVRNFVPE/AHEQI I NHDWEVAA IAKDAYDIEGKT LAP I GAGRIGYRVLERLL PFN PKELL YYQRQAL PKE AEEKVCARRENE]FLAQAD I VTNAPL HATKGL INKELLSK.FKKGAWLVNT ARGAI CVAEDVAAALESGQLRGYGDVWFPQPAPKD-PWRDMRNKYGAGNAMT PLY SGT T LDAD PRYAEGTKNILESFFTGKFDYRPQDIILENGEYVTKAYGKDKK (SEQ IDNO:5) -276- [005341 Mutant Candida bodinil enzyme described in Joumal of Molecular Catalysis B: Enzymatic, Volume 61, Issues 3-4, December 2009, Pages 157-161: MKIVLVLYDAGKH'AADEEKLY GC T ENKLGIANWLKDQGE-L ITlT S D-KEGETSELDKRI PDATI I I T' TP Fl- PAY I T KERL DKAKNLKLVVVAGVG S D I DL DY INQ TGKKI SVLSEVTGSNIt/V VSVAE -IVV MTMLVLVRNFN/VPIEQ I NIDWEVAAIT AKDAYDIESKT I AT IGAGR IGEYRVLERL L PENPKE LL YY S PQAL PK<EAEEK VGARRVEN IEE LVEAADI VT VNAPLEHAGTKGL INEKE L L SRKKKAWLVN T ARGA ICVAEDV'AALE SGQLRGYGGD"WFPQPAPKDPWRDMRNKYGAGNA.MT PYSGITTLDAQ TRYAEGTKNILES FFTGKFDYREQDI LENGEYVYKAYGKEDKK (SEQ ID NO:6) [005351 Mutant Saccharonyces cerevisiae enzyme described in Biochem J. 2002 November 1:367(Pt. 3):841-847: MS-' KGKV-jLLV/LYE GGK HAE EQEKLL',IGCTENELGIRNFI EE- QGYELV,1"/TTIDKDPEPTSTVDRFELKD AEI VIT TPFFPAYI SRNRIAEAPNLKLCVTAVGSDRVDLEAANERKITVTEVTGSNVVSVAEHII VMAT LVLITRNYNG C 1-IQQAINGEWDIAGEVAKNEYDLEDKIISTIVGAGR IGYRVLERLVAFNPKK LLYYARQE.PAEAINRL.NEASKLNRGDIV QRVEKLEDMVAQSDVVTINCPLHKDSRGLFNK.K LISHMKDGA.YLVNTIARGA ICEVAEDVAEAV KSGKLAGYGDVWDKQ PAPKDR PWRTMDNKDRVGN AMITVI SET SLDAQKRYAQGVKNILN3SY . FSKKFDYRPQDI IQNGSYARAY GQKK (SEQ ID NO:7). TABLE 81 NADPH:ferredoxin oxidoreductase Protein GenBank ID GI Number Organism

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petH YP 171276.1 56750575 Synechococcus elongatus PCC 6301

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fpr NP 457968.1 16762351 Salmonella enterica fnrl XP 001697352.1 159478523 Chlamydomonas reinhardtii rfnrl NP_567293.1 18412939 Arabidopsis thaliana aceF NP 414657.1 6128108 Escherichia coli K-12 MG1655 277- TABLE 82 NADP-dependant acylating- acetylaldehyde dehydrogenase Protein GenBank ID GI Number Organism adhB AAB06720. 1 1513071 Thermoanacrobacter pseudethanolicus ATCC 33223 TheetDRAFT 0840 1ZP 08211603. 326390041 Themoanaerobacter ethanolicus JW 200 Cbei 3832 YP 001310903.1 150018649 Clostridium beijerinckii NCIMB 8052 Cbei_4054 YP_0013 11120 .1 150018866 Clostridium beijerinckii NCIMB 8052 Cbei_4045 YP 00 1311111.1 150018857 Clostridium beijerinckii NCMB 8052 [005361 Exemplary genes encoding pyruvate dehydrogenase, pyruvate: ferredoxin oxidoreductase, pyruvate formate lyase, pyruvate decarboxylase, acetate kinase, phosphotransacetylase and acetyl-CoA synthetase are described above in Example IL [005371 Genes encoding enzymes that can facilitate the transport of 1,3-butanediol include glycerol facilitator protein homologs such as those provided below. EXAMPLE X ENGINEERING SA CCHAROMYCES j'EREVISY4E FOR CHEMICAL PRODUCTION [005381 Eukaryotic hosts have several advantages over prokaryotic systems. They are able to support post-translational modifications and host membrane-anchored and organelle-specific enzymes. Genes in eukaryotes typically have introns, which can impact the timing of gene expression and protein structure. [005391 An exemplary eukaryotic organism well suited for industrial chemical production is Saccharonmyces cerevisIae. This organism is well characterized, genetically tractable and -278industrially robust. Genes can be readily inserted, deleted, replaced, overexpressed or underexpressed using methods known in the art. Some methods are plasmid-based whereas others allow for the incorporation of the gene into the chromosome (Guthrie and Fink. Guide to Yeast Genetics and Molecular and Cell Biologyv Part B , Volume 350, Academic Press (2002); Guthrie and Fink, Guide to Yeast Genetics and Molecular and Cell Biology, Part C, lolune 351, Academic Press (2002)). [005401 Plasmid-mediated gene expression is enabled by yeast episomal plasmids (YEps). YEps allow for high levels of expression; however they are not very stable and they require cultivation in selective media. They also have a high maintenance cost to the host metabolism. High copy number plasmids using auxotrophic (e.g., URA3, IRP1, H1S3, LEU2) or antibiotic selectable markers (e.g., Zeo or KanR) can be used, often with strong, constitutive promoters such as PGK I or ACTI and a transcription terrninator-polyadenylation region such as those from CYC 1 or AOX. Many examples are available for one well-versed in the art. These include pVV2 14 (a 2 micron plasmid with URA3 selectable marker) and pVV200 (2 micron plasmid with TRPi1 selectable marker) (Van et al., Yeast 20:739-746 (2003)). Alternatively, relatively low copy plasmids can be used. Again, many examples are available for one well-versed in the art. These include pRS3 13 and pR S315 (Sikorski and Flieter, Genetics 122:19-27 (1989) both of which require that a promoter (e.g., PGKI or ACT1) and a terminator (e.g., CYC1, AOX) are added. [005411 For industrial applications, chromosomal overexpression of genes is preferable to plasmid-mediated overexpression. Tools for inserting genes into eukaryotic organisms such as S. cerevisiae are known in the art. Particularly useful tools include yeast integrative plasmids (YIps), yeast artificial chromosomes (YACS) and gene targeting/homologous recombination. Note that these tools can also be used to insert, delete, replace, underexpress or otherwise alter the genome of the host. 1005421 Yeast integrative plasmids (Ylps) utilize the native yeast homologous recombination system to efficiently integrate DNA into the chromosome. These plasmids do not contain an origin of replication and can therefore only be maintained after chromosomal integration. An exemplary construct includes a promoter, the gene of interest, a terminator, and a selectable -279marker with a promoter, flanked by FRT sites, loxP sites, or direct repeats enabling the removal and recycling of the resistance marker. The method entails the synthesis and amplification of the gene of interest with suitable primers, followed by the digestion of the gene at a unique restriction site, such as that created by the EcoRI and Xhoi enzymes (Vellanki et al., Biotechnol Lett. 29:313-318 (2007)). The gene of interest is inserted at the EcoRI and XhoI sites into a suitable expression vector, downstream of the promoter. The gene insertion is verified by PCR and DNA sequence analysis. The recombinant piasmid is then linearized and integrated at a desired site into the chromosomal DNA of S. cerevisiae using an appropriate transformation method. The cells are plated on the YPD medium with an appropriate selection marker and incubated for 2-3 days. The transformants are analyzed for the requisite gene insert by colony PCR. To remove the antibiotic marker from a construct flanked by loxP sites, a plasmid containing the Cre recombinase is introduced. Cre recombinase promotes the excision of sequences flanked by loxP sites. (Gueldener et al., Nucleic Acids Res 30:e23 (2002)). The resulting strain is cured of the Cre plasmid by successive culturing on media without any antibiotic present, The final strain has a markerless gene deletion, and thus the same method can be used to introduce multiple insertions in the same strain. Alternatively, the FLP-FRT system can be used in an analogous manner. This system involves the recombination of sequences between short Flipase Recognition Target (FR T) sites by the Flipase recombination enzyme (FLP) derived from the 21 plasmid of the yeast Saccharomyces cerevisiace (Sadowski, P. D.. Prog.Nucleic.AcidRes.MoiBioi. 51:53-91 (1995); Zhu and Sadowski JBiol.Chemn. 270:23044 23054 (1995)). Similarly, gene deletion methodologies will be carried out as described in refs. Baudin et al. Nucleic.Acids Res. 21:3329-3330 (1993); Bracimann et al., Yeast 14:115-132 (1998); Giaever et al., Nature 418:387-391 (2002); Longtine et al., Yeast 14:953-961 (1998) Winzeler et al., Science 285:901-906 (1999). [005431 Another powerful approach for manipulating the yeast chromosome is gene targeting. This approach takes advantage of the fact that double stranded DNA breaks in yeast are repaired by homologous recombination. Linear DNA fragments flanked by targeting sequences can thus be efficiently integrated into the yeast genome using the native homologous recombination machinery. In addition to the application of inserting genes, gene targeting approaches are useful -280for genomic DNA manipulations such as deleting genes, introducing mutations in a gene, its promoter or other regulatory elements, or adding a tag to a gene. [00544] Yeast artificial chromosomes (YACs) are artificial chromosomes useful for pathway construction and assembly. YACs enable the expression of large sequences of DNA (100-3000 kB) containing rnultiple genes. The use of YACs was recently applied to engineer flavenoid biosynthesis in yeast (Naesby et al, Microb Cell Fact 8:49-56 (2009)). In this approach, YACs were used to rapidly test randomly assembled pathway genes to find the best combination. [005451 The expression level of a gene can be modulated by altering the sequence of a gene and/or its regulatory regions. Such gene regulatory regions include, for example, promoters, enhancers, introns, and terminators. Functional disruption of negative regulatory elements such as repressors and/or silencers also can be employed to enhance gene expression. RNA based tools can also be employed to regulate gene expression. Such tools include RNA aptarners, riboswitches, antisense RNA, ribozyrnes and riboswitches. [00546] For altering a gene's expression by its promoter, libraries of constitutive and inducible promoters of varying strengths are availa ble. Strong constitutive promoters include pTEF 1, pADHI and promoters derived from glycolytic pathway genes. The pGAL promoters are well studied inducible promoters activated by galactose and repressed by glucose. Another commonly used inducible promoter is the copper inducible promoter pCUPi (Farhi et al, Met Eng 13:474-81 (2011)). Further variation of promoter strengths can be introduced by mutagenesis or shuffling methods. For example, error prone PCR can be applied to generate synthetic promoter libraries as shown by Alper and colleagues (Alper et al, PNAS 102:12678-83 (2005)). Promoter strength can be characterized by reporter proteins such as beta-galactosidase, fluorescent proteins and luciferase. [005471 The placement of an inserted gene in the genome can alter its expression level. For example, overexpression of an integrated gene can be achieved by integrating the gene into repeating DNA elements such as ribosomal DNA or long tenninal repeats. [00548] For exogenous expression in yeast or other eukaryotic cells, genes can be expressed in the cytosol without the addition of leader sequence, or can be targeted to mitochondrion or other -281 organelles, or targeted for secretion, by the addition of a suitable targeting sequence such as a mitochondrial targeting or secretion signal suitable for the host cells. Thus, it is understood that appropriate modifications to a nucleic acid sequence to remove or include a targeting sequence can be incorporated into an exogenous nucleic acid sequence to impart desirable properties. Genetic modifications can also be made to enhance polypeptide synthesis. For example, translation efficiency is enhanced by substituting ribosome binding sites with an optimal or consensus sequence and/or altering the sequence of a gene to add or remove secondary structures. The rate of translation can also be increased by substituting one coding sequence with another to better match the codon preference of the host. EXAMPLE X] EXEMPLARY GENES FOR 1.3-BDO EXPORT 1005491 1,3-butanediol must exit the production organism in order to be recovered and/or dehydrated to butadiene. Genes encoding enzymes that can facilitate the transport of 1,3 butanediol include glycerol facilitator protein homologs such as those provided below. Multidrug resistance transporters that export butanol, including OmrA, LnrA and honologs (see, e.g., Burd and Bhattacharyya, US Patent Application 20090176288) are also suitable transporters for 1,3 butanediol. TABLE 83 Protein GenBanklID Gi number Orgnis glpF NP 418362.1 16131765 Escherichia coli YFL054C NP_116601.1 14318465 Saccharomyces cerevisiae YLL043W NP_01 3057.1 6322985 Saccharomyces cerevisiae KLLA0E00617g XP_453974.1 50307951 Kluvveron'ces lactis ANY 1 1314144 XP 001397337.2 317036426 Aspergillts nIger ANII_3222024 XP_001400456.1 145234170 Aspergillus niger AN/_1_710114 XP_001396373.2 317034445 Aspergillus niger -282- YALJE05665p XP_503595.1 505523 0 Yarrowia iipoytica Y4LJ0F00462p XP 5048201 50554823 Yarrowia lipolytica Om1rA ZP 01543718 118586261 Oenococcus oeni LDrA AA B49750 1890649 Lactococcus lactis EXAMPLE XII PATHWAYS FOR PRODUCING ACETYL-COA FROM PEP AND PY RU VATE [005501 Figure 10 shows numerous pathways for converting PEP and pyruvate to acetyl-CoA, acetoacetvl-C1'oA, and further to products derived from acetoacetyl-CoA such as I ,3-butanediol. Enzymes candidates for the reactions shown in Figure 10 are described below. TABLE 84 1.. n. Oxidoreductase (alcohol to oxo) M 1,1.1 .d Malic enzyme L 1.2.1.a Oxidoreductase aldehydee to acid) .1 1.2.1 .b Oxidoreductase (acyl-CoA to aldehyde) G 1.2. 1.f Oxidoreductase (decarboxylating acyl-CoA to C alidehyde) 2,7.2.a Kinase N 2.8.3.a CoA transferase K 3.1.3.a Phosphatase N 4.1. l.a Decarboxylase A, B, D 6.2.1.a CoA synthetase 6.4.i.a Carboxylase_ D,H [005511 Enzyme candidates for several enzymes in Figure 10 have been described elsewhere in the text. These include acetoacetyl-CoA synthase (Table 70), acetoacetyl-CoA thiolase (Table 42), malonyl-CoA reductase (also called malonate semialdehyde dehydrogenase (acylating) (Tables 35, 46), malate dehydrogenase (Tables 7 and 23). -283- [00552] 1.1.n.a [005531 Malate dehydrogenase or oxidoreductase catalyzes the oxidation of palate to oxaloacetate. Different carriers can act as electron acceptors for enzyrnes in this class. Malate dehydrogenase enzymes utilize NADP or NAD as electron acceptors. Malate dehydrogenase (Step M) enzyme candidates are described above in example I (Table 7, 23). Malate:quinone oxidoreductase enzymes (EC 1. 1.5.4) are membrane-associated and utilize quinones, flavoproteins or vitamin K as electron acceptors. Malate:quinone oxidoreductase enzymes of . coli, Helicobacter pylori and Pseudomonas sVringae are encoded by mqo (Kather et al, J Bacteriol 182:3204-9 (2000); Mellgren et al., JBacteriol 191:3132-42 (2009)). The Cgl2001 gene of C. gluanicumn also encodes an MQ) enzyme (Mitsuhashi et al, Biosci Biotechnol Biochem 70:2803-6 (2006)). TABLE 85 Protein GenBank ID GI Number Organism mIiqo NP 416714.1 16130147 Escherichia coli mqo NP_206886.1 15644716 Hielicobacter pylori nqo NP_790970.1 28868351 Pseucomonas syringe Cg12001 NP _601207.1 19553205 Corvnebacteriun gutanicun [00554 1.1.1.d [00555] Malic enzyme palatee dehydrogenase) catalyzes the reversible oxidative carboxylation of pyruvate to malate. _. coli encodes two malic enzymes, MaeA and MacB (Takeo, J. Biocheni. 66:379-387 (1969)). Although malic enzyme is typically assumed to operate in the direction of pyruvate formation from palate, the NAD-dependent enzyme, encoded by maeA, has been demonstrated to operate in the carbon-fixing direction (Stols and Donnelly, Appl Environ. Microbiol. 63(7) 2695-2701 (1997)), A similar observation was made upon overexpressing the malic enzyme from Ascaris suun in . coli (Stols et al., Appl. Biocheni. Biotechnol. 63-65(1), 153-158 (1997)). The second E. coli malic enzyme, encoded by maeB, is NADP-dependent and also decarboxylates oxaloacetate and other alpha-keto acids (Iwakura et al., J. Biochem. 85(5):1355-65 (1979)). Another suitable enzyme candidate is mel from Zea mays (Furumoto et al, Plant Cell Physiol 41:1200-1209 (2000)), -284- TABLE 86 Protein GenBank ID GI Number Organism maeA NP 415996 90111281 Escherichia coli maeB NP 416958 16130388 Escherichia coli NAD-ME P27443 126732 Ascaris swim M'! P 16243. 1 126737 j Zea ways [005561 1.2.1.a [00557] The oxidation of malonate semialdehyde to malonate is catalyzed by malonate semialdehyde dehydrogenase (EC 1.2.1.15). This enzyme was characterized in Pseudomonas aeruginosa (Nakarnura et a], Biochim fBiophys .cta 50:147-52 (1961)). The NADP and NAD dependent succinate semialdehyde dehydrogenase enzymes of EUg/ena gracilas accept malonate semialdehyde as substrates (Tokunaga et al, Biochem Biophys Act 429:55-62 (1976)). Genes encoding these enzymes has not been identified to date. Aldehyde dehydrogenase enzymes from eukoryotic organisms such as S. cerevisiace, C albicans, Y. lipovtica and A. niger typically have broad substrate specificity and are suitable candidates. These enzymes and other acid forming aldehyde dehydrogenase and aldehyde oxidase enzymes are described earlier and listed in Tables 9 and 30. Additional MSA dehydrogenase enzyme candidates include NAD(P)+-dependent aldehyde dehydrogenase enzymes (EC 1.2.1.3). Two aldehyde dehydrogenases found in human liver, ALDH-1 and ALDH-2, have broad substrate ranges for a variety of aliphatic, aromatic and polycyclic aldehydes (Klvosov, Biochemistry 35:4457-4467 (19 9 6a)). Active ALD-i-2 has been efficiently expressed in E. coli using the GroEL proteins as chaperonins (Lee et al., Biochem.Biohys.Res. Conunun. 298:216-224 (2002)). The rat m itochondrial aldehyde dehydrogenase also has a broad substrate range (Siew et al., Arch.Biochem.Biophys. 176:638-6449 (1976)). The E. coli genes astD and aidI encode NAD+-dependent aldehyde dehydrogenases. AstD is active on succinic semialdehyde (Kuznetsova et al., FEMlS Microbiol Rev 29:263-279 (2005)) and aldH is active on a broad range of aromatic and aliphatic substrates (Jo et al, Appl Microbial Biotechnol 81:51-60 (2008)). -285- TABLE 87 Gene GenBank Accession No. GI No. Organism astD P76217.1 3913108 Escherichia co/i alIH AAC74382.1 1787558 Escherichia coli ALDH-2 P05091.2 118504 Homo sapiens ALDH-2 INP 115792.1 14192933 Rattus norvegicus [005581 1.2.11 [00559] Malonate senialdehyde dehydrogenase (acetylating) (EC 1.2.1.18) catalyzes the oxidative decarboxylation of malonate semialdehyde to acetyl-CoA. Exemplary enzymes are encoded by ddcC of Halomonas sp. JTNK1 (Todd et al, Environ iMicrobiol 12:237-43 (2010)) and Io/A of Lactobacilus case (Yebra et al, AEII 73:3850-8 (2007)). The DdcC enzyme has homologs in A. niger and C. albicans, shown in the table below. The malonate semialdehyde dehydrogenase enzyme in Rattus norv'egicus, Mmsdh, also converts malonate semialdehyde to acetyl-CoA (US 8048624). A malonate semialdehyde dehydrogenase (acetylating) enzyme has also been characterized in Pseudomonasfluorescens, although the gene has not been identified to date (Hayaishi et al, JBioi Chen 236:781-90 (1961)). Methylmalonate semialdehyde dehydrogenase (acetylating) enzymes (EC 1.2.1.27) are also suitable candidates, as several enzymes in this class accept malonate semialdehyde as a substrate including Msdh of Bacillus subtilis (Stines-Chaumeil et al, Biochen J395:107-15 (2006)) and the methvlmalonate semialdehyde dehydrogenase of R. norvegicus (Kedishvii et al, AMethods Enzynol 324:207-18 (2000)). TABLE 88 Protein GenBank ID GI Number Organism ddcC ACV84070.1 258618587 1ladomonas sp. HTNK1 AN 1 1120014 XP 001389265.1 145229913 Aspergi/us niger ALD6 XP 710976.1 68490403 Candida albicans YALIOC01859g XP_501343.1 50547747 Yarrowia lipolytica mmsA 1 YP 257876.1 70734236 Pseudonionasfluorescens nnsA 2 YP 257884.1 70734244 -Pseuomonasluores-eens -286- P40/30 NP_24 8820. 1 15595328 Pseudomonas aeruginosa MmsCh Q02253.1 400269 Rattus norvegicus mnsd/h NP 391855.1 1608 1027 Bacillus subtilis Io/A ABP57762.i 145309085 jLactobacilius case [005601 2.7.2.a 1005611 Pyruvate kinase (Step ION), also known as phosphoenolpyruvate synthase (EC 2.7.9.2), converts pyruvate and ATIP to PEP and AMP. This enzyme is encoded by the PYK1 (Burke et a]., J. Biol. Chem, 258:2193-2201 (1983)) and PYK2 (Boles et al., J. Bacteriol. 179:2987-2993 (1997)) genes in S. cerevisiae. In E. coli, this activity is catalyzed by the gene products of pykF and pykA. Selected homologs of the S cerevisiae enzymes are also shown in the table below. TABLE 89 Protein GenBank ID G1 Number Organism---------------- P YK NP 009362 6319279 Saccharonmyces cerevisiae PYK2 NP 014992 6324923 Saccharonmyces cerevisiae pykF NP 416191.1 16129632 escherichia co/i pyLA NP_416368.1 16129807 Escherichia coli KL LA 023397g N P_456122.1 50312181 K/uvveromyces lactis CaO19.3575 XP 714934.1 68482353 Cancid/a albicans C6a19.11059 XP 714997.1 68482226 Candida albicans YALIOF091Rp P_ 505195 210075987 Yarrvwia /inolvtica ANI 1 1126064 XP 001391973 1452386 52 Asergilus niger [005621 2.8.3.a 1005631 Activation of malonate to malonyl-CoA is catalyzed by a CoA transferase in EC class 2.8.3.a. Malonyl-CoA:acetate CoA transferase (EC 2.8.3.3) enzymes have been characterized in Pseud/omonas species including Pseudomonasfluorescens and Pseud/omonas puti/a (Takarnura et al, Biochem Int 3:483-91 (1981); Hayaishi et al, J Biol Chem 215:125-36 (1955)). Genes associated with these enzymes have not been identified to date. A mitochondrial CoA transferase found in Rattus norvegicus liver also catalyzes this reaction and is able to utilize a range of CoA donors and acceptors (Deana et al Biochen Int 26:767-73 (1992)). Several CoA transferase enzymes described above can also be applied to catalyze step K of Figure 10. These enzymes -287include acetyl-CoA transferase (Table 26), 3-HB CoA transferase 8), acetoacetyl-CoA transferase (table 55), SCOT (table 56) and other CoA transferases (table 57). [005641 3.1.3.a [00565] Phosphoenolpyruvate phosphatase (EC 3.1.3,60, Step ION) catalyzes the hydrolysis of PEP to pyruvate and phosphate. Numerous phosphatase enzymes catalyze this activity, including alkaline phosphatase (EC 3.1.3.1), acid phosphatase (EC 3.1.3.2), phosphoglycerate phosphatase (EC 3.1.3.20) and PEP phosphatase (EC 3.1.3.60), PEP phosphatase enzymes have been characterized in plants such as Vignia radiate, Bruguiera sexangula and Brassica nigra. The phytase from Aspergillusfiinigates the acid phosphatase from Homo sapiens and the alkaline phosphatase of E coli also catalyze the hydrolysis of PEP to pyruvate (Brugger et al, Appi M1icrobiol Biotech 63:383-9 (2004); Hayman et al, 3iochem J 261:601-9 (1989); et al, The Enzymes 3d Ed. 4:37 3-415 (1971))). Similar enzymes have been characterized in Canpylobacter jejuni (van Mourik et al., Microbiol. 154:584-92 (2008)),. Saccharoynces cerevs iae (Oshima et al., Gene 179:171-7 (1996)) and Staphylococcus aureus (Shah and Blobel, J Bacterial. 94:780-1 (1967)). Enzyme engineering and/or removal of targeting sequences may be required for alkaline phosphatase enzymes to function in the cytoplasm. TABLE 90 Protein GenBank ID GI Number 'IOrganismi phyA 000092,1 41017447 Aspergillusfianigatus A cpS P13686.3 56757583 lHomo sapiens phoA NP 414917.2 49176017 Fscherichia coli phoX ZI_ 01 072054.1 8615385 1 Campylobacterjejuni P-108 AAA34871 1 172164 Saccharomynces cerewsiae SaurJH 12706 YP 001317815.1 150395140 Staphylococcus aureus [00566] 4.1.1.a [00567] Several reactions in Figure 10 are catalyzed by decarboxylase enzymes in EC class 4,1.1, including oxaloacetate decarboxylase (Step [3), malonyl-CoA decarboxylase (step D) and pyruvate carboxylase or carboxykinase (step A). -288- [005681 Carboxylation of phosphoenolpyruvate to oxaloacetate is catalyzed by phosphoenolpyruvate carboxylase (1C 4.1,1 31). Exemplary PEP carboxylase enzymes are encoded byppc in E. coli (Kai et al., Arch. Biochein. Biophys. 414:170-179 (2003),ppcA in Methylobacterim extorquens Aifl (Arps et al., J Bacteriol. 175:3776-3783 (1993). and ppc in Corynebacteriun glutainicum (Eikmanns et al, Mo4l. Gen. Genet. 218:330-339 (1989). TABLE 91 Protein GenBank ID G Number Organism Ppc NP 418391 16131794 Escherichia coli pp c A AB5 8883 28572162 Methylobacteriun exiorquens PIc A 1353270 80973080 Corynebacterim giutamicumz [005691 An alternative enzyme for carboxylating phosphoenolpyruvate to oxaloacetate is PEP carboxykinase (EC 4.1.1.32, 4. 1.1 .49), which simultaneously forms an A TP or GIP. In most organisms PEP carboxykinase serves a gluconeogenic function and converts oxaloacetate to PEP at the expense of one ATP. S. cerevisiae is one such organism whose native PEP carboxykinase, PCK, serves a gluconeogenic role (Valdes-Hevia et al., FEBS Lett. 258:3 13-316 (1989). E. coli is another such organism, as the role of PEP carboxykinase in producing oxaloacetate is believed to be minor when compared to PEP carboxylase (Kim et al., Appl. Environ. Microbiol. 70:1238 1241 (2004)). Nevertheless, activity of the native E. coli PEP carboxykinase from PEP towards oxaloacetate has been recently demonstrated in ppc mutants of E. coli K-i 2 (Kwon et al., J Microbiol. Biotechnol. 16:1448-1452 (2006)). These strains exhibited no growth defects and had increased succinate production at high Na[HC0 3 concentrations. Mutant strains of E. co/i can adopt Pck as the dominant C0 2 -fixing enzyme following adaptive evolution (Zhang et al. 2009). In some organisms, particularly rumen bacteria, PEP carboxykinase is quite efficient in producing oxaloacetate from PEP and generating ATP. Examples of PEP carboxykinase genes that have been cloned into E. coli include those from Mannheimnia succiniciproducens (Lee et al., Biotechnol. Bioprocess Eng. 7:95-99 (2002)), Anaerobiospirillwn succiniciproducens (Laivenieks et al., AppL. Environ. Microbiol. 63:2273-2280 (1997), and Actinobacillus succznogenes (Kim et al. supra). The PEP carboxykinase enzyme encoded by Haemophilus influenza is effective at forming oxaloacetate from PEP. Another suitable candidate is the PEPCK enzyme from Mfaegathyrsus maxinius, which has a low Km for CO 2 , a substrate thought -289to be rate-limiting in the K coli enzyme (Chen et al., Plant Physiol 128:160-164 (2002); Cotelesage et al., Int.J Biochem.Cell Biol. 39:1204-1210 (2007)). The kinetics of the (P dependent pepck gene product from Cupriavidus necator favor oxaloacetate formation (U S8048624 and Lea et al, Amino A cids 20:225-41 (2001)). TABLE 92 Protein GenBank ID G Number Organism PCKI NP 013023 1 6322950 Saccharonvces cerevisiae pk |NP_417862.1 16131280 Escherichia coli pckA |YP 089485.1 |52426348 Mannheinia succiniciproducens pckA :009460.1 3122621 Anaerobiospirilun succiniciproducens pEck _4 Q6W6X5 75440571 Actinobacills succinogenes p bkiA P-43 923. 1 1 1172 5 73 Haenophi/us influenza AF532733.1:1.1929 AAQ10076.1 33329363 Megathvrsus nIaximus pepck YP 728135.1 113869646 Cupriavidus necator [00570] Oxaloacetate decarboxylase catalyzes the decarboxylation of oxaloacetate to malonate semialdehyde. Enyines catalyzing this reaction include /cgd of 1vcobacterium tuberculosis (GenlBank ID: 050463.4, GI: 160395583). Enzymes evolved from kgd with improved activity and/or substrate specificity for oxaloacetate have also been described (US patent 8048624). Additional enzymes useful for catalyzing this reaction include keto-acid decarboxylases shown in the table below. TABLE 93 EC number Name 4.1.1.1 Pynivate decarboxylase 4.1 1.7 Benzoylformate decarboxylase 4.1.1.40 Hydroxypyruvate decarboxylase 4.1.1 .43 Ketophenylpyruvate decarboxylase 4I.1 1.71 Alpha-ketoglutarate decarboxylase 4,.1. 1.72 Branched chain keto-acid decarboxylase 4.1.1.74 Indolepyruvate decarboxylase 4.1.1.75 2-Ketoarginine decarboxylase 4. . 1.79 Sulfopyruvate decarboxylase 4.1.1.80 Hydroxyphenylpyruvate decarboxylase 4.1 .82 Phosphonopyruvate decarboxylase -290- [005711 The decarboxylation of keto-acids is catalyzed by a variety of enzymes with varied substrate specificities, including pyruvate decarboxylase (EC 4.1 1. f), benzovlformate decarboxylase (EC 4.1 .1.7), alpha-ketoglutarate decarboxylase and branched-chain alpha ketoacid decarboxylase. Pyruvate decarboxylase (PDC), also termed keto-acid decarboxylase, is a key enzyme in alcoholic fermentation, catalyzing the decarboxylation of pyruvate to acetaldehvde. The PDCI enzyme from Saccharomyces cerevisiae has a broad substrate range for aliphatic 2-keto acids including 2-ketobutyrate, 2-ketovalerate, 3-hydroxypyruvate and 2 phenylpyruvate (22). This enzyme has been extensively studied, engineered for altered activity, and functionally expressed in E. coli (Killenberg-Jabs et al., EurJBiochem. 268:1698-1704 (2001); Li et al.. Biochenistry. 38:10004-10012 (1999); ter Schure et al., Appl.Environ.Microbiol 64:1303-1307 (1998)). The PDC from Zymomonas mobilus, encoded by pdc, also has a broad substrate range and has been a subject of directed engineering studies to alter the affinity for different substrates (Siegert et al., Protein Eng Des Sel 18:345-357 (2005)). The crystal structure of this enzyme is available (Killenberg-Jabs et al., Eur.J.Biochem. 268:1698-1704 (200 1)). Other well-characterized PDC candidates include the enzymes from Acetobacter pasteurians (Chandra et al., 176:443-451 (200 1)) and Kluvveromiyces lactis (Krieger et al., 269:3256-3263 (2002)). TABLE 94 Pro tein GenBank ID GI Number Organism pckc P06672.1 118391 Zvmomonas mobilis p dc 1 P06169 30923172 Saccharonmyces cerev'isae pdc Q8 L3 88 203 85 191 Acetobacter pasteurians pdcl Q12629 52,88279 Kluvveronvces lactis 1005721 Like PDC, benzoyiformate decarboxylase (EC 4.1.1.7) has a broad substrate range and has been the target of enzyme engineering studies. The enzyme from Pseudononas putida has been extensively studied and crystal structures of this enzyme are available (Polovnikova et al., 42:1820-1830 (2003); Hasson et al., 37:9918-9930 (1998)). Site-directed mutagenesis of two residues in the active site of the Pseudomonas putida enzyme altered the affinity (Km) of naturally and non-naturally occurring substrates (Siegert et al., Protein Eng Des Sel 18:345-357 -291- (2005)). The properties of this enzyme have been further modified by directed engineering (Lingen et aL, Chembiochem. 4:721-726 (2003); Lingen et al., Protein Eng 15:585-593 (2002)). The enzyme from Pseudomnonas aeruginosa, encoded by mdlC has also been characterized experimentally (Barrowman et a]., 34:57-60 (1986)), Additional gene candidates from Pseudomonas stutzeri, Pseudomonasfiorescens and other organisms can be inferred by sequence homology or identified using a growth selection system developed in Pseudomonas putida (lenning et al., Appl.Environ.Microbiol. 72:7510-75 17 (2006)). TABLE 95 Protein GenBatnk ID GI Number Organism md/C P20906.2 39157 57 Pseudomonas putia md/C Q9HUR2. 1 815339678 Pseudomonas aeruginosa dpgB ABN80423.1 126202 18 Pseudomonas stutzei ivB-1 YP_260581.1 70730840 Pseudomonas fluorescens [005731 A third enzyme capable of decarboxylating 2-oxoacids is alpha-ketoglutarate decarboxylase (KGD, [IC 4.1.1.71). The substrate range of this class of enzymes has not been studied to date. An exemplarly KDC is encoded by kad in Mvcobacteriwn tuberculosis (Tian et al., PAS 102:10670-10675 (2005)). KDC enzyme activity has also been detected in several species of rhizobia including Bradyrhizobium japonicum and Mesorhizobium loti (Green et al., J Bacteriol 182:2838-2844 (2000)). Although the KDC-encoding gene(s) have not been isolated in these organisms, the genome sequences are available and several genes in each genome are annotated as putative KDCs. A KDC from Euglena gracilis has also been characterized but the gene associated with this activity has not been identified to date (Shigeoka et al., Arch.Biochem.Biophys. 288:22-28 (1991)). The first twenty amino acids starting from the N terminus were sequenced MVITYKAPVK[)VKFLLDKVFKV (SEQ 1D NO:8) (Shigeoka and 'akano, Arch.Biochem.Biophys. 288:22-28 (1991)), The gene could be identified by test candidate genes containing this N-terminal sequence for KDC activity. A novel class of AKG decarboxylase enzymes has recently been identified in cyanobacteria such as Svnechococcus sp. PCC 7002 and homologs (Zhang and Bryant, Science 334:1551-3 (2011)), -292- TABLE 96 Protein GenBank ID C1 Number Organism kgd 050463.4 160395583 AMfycobacteriun tuberculosis kgd NP 767092.1 2737p5563 BradvrhizobiunjaponicumUSDA110 kngd NP_105204.1 13473636 M'fesorhizobium loti ivB ACB00744.1 169887030 Synechococcus sp. PCC 7002 [005741 A fourth candidate enzyme for catalyzing this reaction is branched chain alpha ketoacid decarboxylase (BCKA). This class of enzyme has been shown to act on a variety of compounds varying in chain length from 3 to 6 carbons (Oku et al., J Biol Chemn. 263:18386 18396 (1988); Smit et al., App/ Environ Microbiol 71:303-311 (2005)). The enzyme in Lactococcus lactis has been characterized on a variety of branched and linear substrates including 2-oxobutanoate, 2-oxohexanoate, 2-oxopentanoate, 3-methyl-2-oxobutanoate, 4 methyl-2-oxobutanoate and isocaproate (Smnit et al, App/ Environ Microbiol 71:303-311 (2005)). The enzyme has been structurally characterized (Berg et al., Science. 318:1782-1786 (2007)). Sequence alignments between the Lactococcus lactis enzyme and the pyruvate decarboxylase of Zynonionas mobi/us indicate that the catalytic and substrate recognition residues are nearly identical (Siegert et al., Protein Eng Des Sel 18:345-357 (2005)), so this enzyme would be a promising candidate for directed engineering. Several ketoacid decarboxylases of SaccharonYces cerevisiae catalyze the decarboxylation of branched substrates, including ARO10, PDC6, PDC5, PDCl and TH13 (Dickenson et al, J Biol Chemn 275:10937-42 (2000)). Yet another BCKAD enzyme is encoded by rv0853c of Mycobacteriun tuberculosis (Werther et al, JBiol Chem 283:5344-54 (2008)). This enzyme is subject to allosteric activation by alpha ketoacid substrates. Decarboxylation of alpha-ketoglutarate by a BCKA was detected in Bacillus subtilis; however, this activity was low (5%) relative to activity on other branched-chain substrates (Oku and Kaneda, J Biol Chem. 263:18386-18396 (1988)) and the gene encoding this enzyme has not been identified to date. Additional BCKA gene candidates can be identified by homology to the Lactococcus actis protein sequence. Many of the high-scoring BLASTp hits to this enzyme are annotated as indolepyruvate decarboxylases (EC 4.1.1.74). Indolepyruvate decarboxylase (IPDA) is an enzyme that catalyzes the decarboxylation of indolepyruvate to -293indoleacetaldehyde in plants and plant bacteria. Recombinant branched chain alpha-keto acid decarboxylase enzymes derived from the El subunits of the mitochondrial branched-chain keto acid dehydrogenase complex from Homo sapiens and Bos taurus have been cloned and functionally expressed in E. coli (Davie et al., J.BiolChem. 267:16601-16606 (1992); Wynn et al., J.Biol.Chen. 267:12400-12403 (1992); Wynn et at, J.Biol.Cieni. 267:1881-1887 (1992)). In these studies, the authors found that co-expression of chaperonins GroEL and GroES enhanced the specific activity of the decarboxylase by 500-fold (Wynn et al., J.Biol.Chem. 267:12400 12403 (1992)). These enzymes are composed of two alpha and two beta subunits. TABLE 97 Protein Gen Bank ID GI Number Organism kdc1 AAS49166.1 44921617 Lactococcus lactis PDC6 NP_010366.1 6320286 Saccharoinces cerevisiae PDC5 NP 013235.1 6323163 Saccharonnces cerevisiae PDC_ P06169 30923172 Sacharoinvees cereviae AROiO NP 010668.1 63205 88 Saccharonmvces cerevisiae TlE NP 010203.1 6320123 Saccharonvces cerevisiae rv0853c 053865.1 81343167 Mvcobacteriut wberculosis BCKDH1 B NP_898871.1 34101272 Honio sapiens BCKD/A NP_000700,1 11386135 Homo sapiens B CKDB 11 P21839 1 15502434 Bos taurus BC KDIA P11178 129030 Bos taurs [005751 3-Phosphonopyruvate decarboxylase (EC 4.1 . 1.82) catalyzes the decarboxylation of 3 phosphonopyruvate to 2-phosphonoacetaldeh yde. Exemplary phosphonopyruvate decarboxylase enzymes are encoded by dhpF of Streptonyces luridus, ppd of Streptonmyces viridochroniogenes, fomi2 of Streptonvces wednorensis and bcpC of Streptotmyces hygroscopius (Circel lo et al, Chen Biol 17:402-11 (2010); Blodgett et al, FEMlS Microbiol Lett 163:149-57 (2005); Hidaka et al, Mol Gen Genet 249:274-80 (1995); Nakashita et a, Biochim Biophys Acta 1490:159-62 (2000)). The Bacteroides agilis enzyme, encoded by aepY, also decarboxylates pyruvate and sulfopyruvate (Zhang et al, J Biol Chein 278:41302-8 (2003)). -294- TABLE 98 Protein GenBank ID GI Number Organism dhpF ACZ 13457.1 268628095 Streptomc es [idis Ppd CA A14045.1 686977 16 StrepjtomIyce's viridlochromnogenes Foin2 BAA32496.1 1061008 ___ tregon 1 s nm oensis aepY AAG26466.1 11023509 Bactcroid agili_____s [005761 Many oxaloacetate decarboxylase enzymes such as the eda gee product in E. coli (EC 4.1.1.3), act on the terminal acid of oxaloacetate to form pyruvate. Because decarboxylation at the 3-keto acid position competes with the malonate semialdehyde fonming decarboxylation at the 2-keto-acid position, this enzyme activity can be knocked out in a host strain with a pathway proceeding through a mnalonate sernilaldehyde intermediate. [005771 Malonyl-CoA decarboxylase (EC 4.1.1.9) catalyzes the decarboxylation of malonyl CoA to acetvl-CoA. Enzymes have been characterized in Rhizobium legoninosaruni and Acinetobacter calcoaceticus (An et al, Eur JBiochem 257: 395-402 (1998); Koo et al, EurJ Biochen 266:683-90 (1999)). Similar enzymes have been characterized i .Streptonyces erythreus (Hunaiti et al, Arch Biochen Biophys 229:426-39 (1984)). A recombinant human malonyl-CoA decarboxylase was overexpressed in E. coli (Zhou et al, Prot Expr Pur 34:261-9 (2004)). Methylmalonyl-CoA decarboxylase enzymes that decarboxylate malonyl-CoA are also suitable candidates. For example, the Veillonella parvula enzyme accepts nalonyl-CoA as a substrate (Hilpert et al, Nature 296:584-5 (1982)). The E. coli enzyme is encoded by ygfG (Benning et al., Biochemistry. 39:4630-4639 (2000); Haller et al., Biochemistry. 39:4622-4629 (2000)). The stereo specificity of the E. coli enzyme was not reported, but the enzyme in Propionigeniun modestun (Bott et al., Eur.JBiochein. 250:590-599 (1997)) and Veillone/la parvula (Huder et al.,. Biol.Chem. 268:24564-24571 (1993)) catalyzes the decarboxylation of the (S)-stereoisomer of methylnalonyl-CoA (Hoffmann et al., FEBS.Lett. 220:121-125 (1987)). The enzymes from P. nodestun and V parvula are comprised of multiple subunits that riot only decarboxylate (S)-methylmalonyl-CoA, but also create a pump that transports sodium ions across the cell membrane as a means to generate energy. -295- TABLE 99 Protein GenBank ID GI Number Organism YgfG NP_417394 90111512 Escherichia co/i matA Q9ZIP6 75424899 Rhizobium leguninosarwn InwcD AAB9 7628.1 2804622 Acinetobacter caicoaceU enus incE AAF20287.1 6642782 Acinetobacter calcoaceticus mdcA A AB97627.1 2804621 Acinetobacter calcoaceticus ndcC AAB97630.1 2804624 Acinetobacter calcoaceticus mcd NP 036345.2 110349750 Homo sapiens nunA CA-A05137 2706398 Propionigen im modestum nndD CAA05138 2706399 Propionigenium motestum mindC CAA05139 2706400 Propionigenium modestum mmdt/B CAA05 140 2706401 Propionigeniunm modestun mndA CA A80872 415915F Veillonela parvula mindC CAA80873 415916 Veillonella paivua mindE CAA80874 415917 Veillonella parvula inudD CAA80875 415918 Ve ilonella parvula mmdBf CAA80876 415919 Veillonela parvula 1005781 6.2.1.a [005791 Activation of malonate to malonyl-CoA is catalyzed by a CoA synthetase in EC class 6.2.1 .a. CoA synthetase enzymes that catalyze this reaction have not been described in the literature to date. Several CoA synthetase enzymes described above can also be applied to catalyze step K of Figure 10. These enzymes include acetyl-CoA synthetase (Table 16, 25) and ADP forming CoA synthetases (Table 17). [005801 6.4.1.a [005811 Pyruvate carboxylase (EC 6.4.1.1) converts pyruvate to oxaloacetate at the cost of one ATP (step H). Exemplary pyruvate carboxylase enzymes are encoded by PYC1 (Walker et al., Biochem. Bioph ys. Res. Common. 176:1210-1217 (1991) and PYC2 (Walker et al., supra) in Saccharomyces cerevisiae, and pyc in Mycobacterinu smegmatis (Mukhopadh yay and Purwantini, Biochim. Biophys. Acta 1475:191-206 (2000)). -296- TABLE 100 Protein GenBank ID GI Number Organism PYC1 NP 011453 6321376 Saccharomyces cerevisiae PYC2 NP 009777 6319695 Saccharonyces cerevisiae PIc Y11 890857".1 118470447 M4vcobactcriaz Sillegiatis [005821 Acetyl-CoA carboxylase (EC 6.4.1.2) catalyzes the ATP-dependent carboxylation of acetyl-CoA to malonyl-CoA. This enzyme is biotin dependent and is the first reaction of fatty acid biosynthesis initiation in several organisms. Exemplary enzymes are encoded by accABCD of E. coli (Davis et al, JBio Chem 275:28593-8 (2000)), ACCI of Saccharomyces cerevisiae and homologs (Sumper et al, Methods Enzym 71:34-7 (1981)). TABLE 101 Protein GenBank ID GI Numiber Organism A CC CAA96294.1 1302498 SaccharomYces cerevisiae KLLA 0F06072g XP_455355.1 50310667 Klveromyces iactis A CCI XP 718624.1 6,8474 502 CTandida albicans YALIOC! 40 Zp_ XPI - 5 017 21.1 50548503 Yarrowia lipoivtica ANY 1 1724104 XP 001395476.1 145246454 Asperg ;ilus niger accA AAC73296. 1 1786382 Escherichia coli aceB AAC76287.1 1789653 Escherichia coli accC AAC76288.1 1789654 Escherichia coli accD AAC75376.1 1788655 Escherichia coli 5. SEQUENCE LISTING [005831 The present specification is being filed with a computer readable form (CRF) copy of the Sequence Listing. The CRF entitled 12956-192 SEQLIST.txt, which was created on September 7, 2012 and is 18,766 bytes in size, is identical to the paper copy of the Sequence Listing and is incorporated herein by reference in its entirety. 1005841 Throughout this application various publications have been referenced. The disclosures of these publications in their entireties, including GenBank and GI number -297publications, are hereby incorporated by reference in this application in order to more fully describe the state of the art to which this invention pertains. [00585] Although the invention has been described with reference to the examples and embodiments provided above, it should be understood that various modifications can be made without departing from the spirit of the invention provided herein. [00586] In the claims which follow and in the preceding description of the invention, except where the context requires otherwise due to express language or necessary implication, the word "comprise" or variations such as "comprises" or "comprising" is used in an inclusive sense, i.e. to specify the presence of the stated feature but not to preclude the presence or addition of further features in various embodiments of the invention. [00587] It is to be understood that, if any prior art publication is referred to herein, such reference does not constitute an admission that the publication forms a part of the common general knowledge in the art, in Australia or any other country. -298-

Claims (17)

1. A non-naturally occurring microbial organism comprising a 1,3-BDO pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO, and wherein the organism: i. has lower or no enzymatic activity that converts acetoacetyl-CoA to acetoacetate as compared to a wild-type version of the organism; ii. comprises a disruption in an endogenous nucleic acid encoding an enzyme that converts acetoacetyl-CoA to acetoacetate; iii. expresses an attenuated acetoacetyl-CoA hydrolase or transferase; or iv. comprises a disruption in an endogenous nucleic acid encoding an acetoacetyl-CoA hydrolase or transferase.

2. The organism of claim 1 comprising a disruption in an endogenous nucleic acid encoding an acetoacetyl-CoA hydrolase or transferase.

3. The organism of claim 1 or 2, (1) wherein the organism i. has lower or no enzymatic activity that converts 3-hydroxybutyryl-CoA to 3-hydroxybutyrate as compared to a wild-type version of the organism; ii. comprises a disruption in an endogenous nucleic acid encoding an enzyme that converts 3-hydroxybutyryl-CoA to 3-hydroxybutyrate; iii. expresses an attenuated 3-hydroxybutyryl-CoA hydrolase or transferase; or iv. comprises a disruption in an endogenous nucleic acid encoding a 3 hydroxybutyryl-CoA hydrolase or transferase; (2) wherein the organism: i. has lower or no enzymatic activity that converts 3-hydroxybutyraldehyde to 3-hydroxybutyrate as compared to a wild-type version of the organism; 299 ii. comprises a disruption in an endogenous nucleic acid encoding an enzyme that converts 3-hydroxybutyraldehyde to 3-hydroxybutyrate; iii. expresses an attenuated 3-hydroxybutyraldehyde dehydrogenase; or iv. comprises a disruption in an endogenous nucleic acid encoding a 3 hydroxybutyraldehyde dehydrogenase; (3) wherein the organism: i. has lower or no enzymatic activity that catalyzes 1,3-butanediol to 3 oxobutanol as compared to a wild-type version of the organism; ii. comprises a disruption in an endogenous nucleic acid encoding an enzyme that catalyzes 1,3-butanediol to 3-oxobutanol; iii. expresses an attenuated 1,3-butanediol dehydrogenase; or iv. comprises a disruption in an endogenous nucleic acid encoding a 1,3 butanediol dehydrogenase; (4) wherein the organism: i. has lower or no enzymatic activity that converts G3P to glycerol as compared to a wild-type version of the organism; ii. comprises a disruption in an endogenous nucleic acid encoding an enzyme that converts G3P to glycerol; iii. expresses an attenuated G3P dehydrogenase or G3P phosphatase; or iv. comprises a disruption in an endogenous nucleic acid encoding a G3P dehydrogenase or a G3P phosphatase; (5) wherein the organism: i. has lower or no enzymatic activity that converts pyruvate to acetaldehyde as compared to a wild-type version of the organism; ii. comprises a disruption in an endogenous nucleic acid encoding an enzyme that converts pyruvate to acetaldehyde; iii. expresses an attenuated pyruvate decarboxylase; or 300 iv. comprises a disruption in an endogenous nucleic acid encoding a pyruvate decarboxylase; or (6) wherein the organism: i. has lower or no enzymatic activity that converts acetyl-CoA to ethanol as compared to a wild-type version of the organism; ii. comprises a disruption in an endogenous nucleic acid encoding an enzyme that converts acetyl-CoA to ethanol; iii. expresses an attenuated ethanol dehydrogenase or acetaldehyde dehydrogenase;or iv. comprises a disruption in an endogenous nucleic acid encoding an ethanol dehydrogenase or acetaldehyde dehydrogenase.

4. The organism of claim 3, wherein the organism i. has lower or no enzymatic activity that converts 3-hydroxybutyryl-CoA to 3-hydroxybutyrate as compared to a wild-type version of the organism; ii. comprises a disruption in an endogenous nucleic acid encoding an enzyme that converts 3-hydroxybutyryl-CoA to 3-hydroxybutyrate; iii. expresses an attenuated 3-hydroxybutyryl-CoA hydrolase or transferase; or iv. comprises a disruption in an endogenous nucleic acid encoding a 3 hydroxybutyryl-CoA hydrolase or transferase.

5. The organism of claim 4 wherein the organism comprises a disruption in an endogenous nucleic acid encoding a 3-hydroxybutyryl-CoA hydrolase or transferase

6. The organism of any one of claims 1 to 5, wherein the 1,3-BDO pathway enzyme is selected from the group consisting of 4B, 4C, 4D, 4E, 4F, 4G, 4H, 41, 4J, 4L, 4N, 40, 7E, and 7F; wherein 4B is an Acetoacetyl-CoA reductase (CoA-dependent, alcohol forming); 4C is a 3-oxobutyraldehyde reductase (aldehyde reducing); 4D is a 4-hydroxy-2-butanone reductase, 4E is an Acetoacetyl-CoA reductase (CoA-dependent, aldehyde forming), 4F is a 3-oxobutyraldehyde reductase (ketone reducing), 4G is a 3-hydroxybutyraldehyde 301 reductase, 4H is an Acetoacetyl-CoA reductase (ketone reducing); 41 is a 3 hydroxybutyryl-CoA reductase (aldehyde forming); 4J is a 3-hydroxybutyryl-CoA reductase (alcohol forming); 4L is an acetoacetate reductase; 4N is a 3-hydroxybutyrate reductase; 40 is a 3-hydroxybutyrate dehydrogenase; 7E is an acetyl-CoA carboxylase; and 7F is an acetoacetyl-CoA synthase.

7. The organism of any one of claims 1 to 6, wherein the 1,3-BDO pathway comprises a pathway selected from the group consisting of: i. 4A, 4E, 4F and 4G; ii. 4A, 4B and 4D; iii. 4A, 4E, 4C and 4D; iv. 4A, 4H and 4J; v. 4A, 4H, 4I and 4G; vi. 4A, 4H, 4M, 4N and 4G; vii. 4A, 4K, 40, 4N and 4G; viii. 4A, 4K, 4L, 4F and 4G ix. 7E, 7F, 4E, 4F and 4G; x. 7E, 7F, 4B and 4D; xi. 7E, 7F, 4E, 4C and 4D; xii. 7E, 7F, 4H and 4J; xiii. 7E, 7F, 4H, 41 and 4G; xiv. 7E, 7F, 4H, 4M, 4N and 4G; xv. 7E, 7F, 4K, 40, 4N and 4G; and xvi. 7E, 7F, 4K, 4L, 4F and 4G; wherein 4A is an Acetoacetyl-CoA thiolase; 4B is an Acetoacetyl-CoA reductase (CoA dependent, alcohol forming); 4C is a 3-oxobutyraldehyde reductase (aldehyde reducing); 4D is a 4-hydroxy-2-butanone reductase, 4E is an Acetoacetyl-CoA reductase (CoA 302 dependent, aldehyde forming), 4F is a 3-oxobutyraldehyde reductase (ketone reducing), 4G is a 3-hydroxybutyraldehyde reductase, 4H is an Acetoacetyl-CoA reductase (ketone reducing); 41 is a 3-hydroxybutyryl-CoA reductase (aldehyde forming); 4J is a 3 hydroxybutyryl-CoA reductase (alcohol forming); 4K is an acetoacetyl-CoA transferase, an acetoacetyl-CoA hydrolase, an acetoacetyl-CoA synthetase, or a phosphotransacetoacetylase and acetoacetate kinase; 4L is an acetoacetate reductase; 4M is a 3-hydroxybutyryl-CoA transferase, hydrolase, or synthetase; 4N is a 3 hydroxybutyrate reductase; 40 is a 3-hydroxybutyrate dehydrogenase; 7E is an acetyl CoA carboxylase; and 7F is an acetoacetyl-CoA synthase.

8. The organism of claim 7, wherein the 1,3-BDO pathway comprises 4A, 4H, 41 and 4G.

9. The organism of any one of claims 1 to 8, wherein the endogenous and/or exogenous nucleic acid is an endogenous nucleic acid.

10. The organism of any one of claims 1 to 9, wherein the endogenous and/or exogenous nucleic acid is an exogenous nucleic acid.

11. The organism of claim 10, wherein said organism comprises two, three, four, five, or six exogenous nucleic acids each encoding a 1,3-BDO pathway enzyme.

12. The organism of claim 10 or 11, wherein said at least one exogenous nucleic acid is a heterologous nucleic acid.

13. The organism of any one of claims 1 to 12, wherein said organism further comprises: (1) a pentose phosphate pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding a pentose phosphate pathway enzyme selected from the group consisting of glucose-6-phosphate dehydrogenase, 6 phosphogluconolactonase, and 6 phosphogluconate dehydrogenase (decarboxylating); or (2) an Entner Doudoroff pathway, wherein said organism comprises at least one endogenous and/or exogenous nucleic acid encoding an Entner Doudoroff pathway enzyme selected from the group consisting of glucose-6-phosphate dehydrogenase, 6 phosphogluconolactonase, phosphogluconate dehydratase, and 2-keto-3-deoxygluconate 6-phosphate aldolase. 303

14. The organism of any one of claims 1 to 13, wherein said organism is in a substantially anaerobic culture medium.

15. A method for producing 1,3-BDO, comprising culturing the organism of any one of claims 1 to 14 under conditions and for a sufficient period of time to produce 1,3-BDO.

16. An organism according to claim 1, substantially as herein described or exemplified.

17. A method according to claim 15, substantially as herein described or exemplified. 304