EA044153B1 - KNOCKOUTS IN THE GENES OF WOOD-LYNGDAHL MICROORGANISMS - Google Patents

Description

Cross reference to related application

This application claims benefit to U.S. Provisional Patent Application No. 62/565,000, filed September 28, 2017, which is incorporated herein by reference in its entirety.

State of the art

It has long been discovered that catalytic processes, such as the Fischer-Tropsch process, can be used to convert gases containing carbon dioxide (CO2), carbon monoxide (CO) and/or hydrogen ( _H2 ), such as industrial off-gas or synthesis gas. gas, into a variety of fuels and chemicals. However, recently, gas fermentation has emerged as an alternative platform for the biological fixation of such gases. In particular, C1-fixing microorganisms have been demonstrated to convert gases containing CO ₂ , CO and/or H ₂ into products such as ethanol and 2,3-butanediol. However, efficient production of such products may be limited by slow microbial growth, limited gas uptake, sensitivity to toxins, or leakage of carbon substrates into undesirable byproducts. Accordingly, there remains a need for recombinant microorganisms with improved characteristics.

Description of the figures

The figure is a diagram showing the main production pathways and key metabolic nodes (indicated by boxes) in Wood-Ljungdahl microorganisms. Improving the flow of carbon through these nodes, for example by disrupting the expression of certain genes, improves the production of products obtained in subsequent stages.

Description of the invention

The present invention provides non-naturally occurring microorganisms containing at least one disrupted gene. In the microorganisms of the present invention, carbon flow is strategically diverted from non-essential or unwanted products to products of interest. In some embodiments, these disrupted genes divert carbon flow away from non-essential or unwanted metabolic nodes through targeted metabolic nodes for improved production of products located downstream of these targeted metabolic nodes.

The microorganisms of the present invention are derived from parent bacteria, e.g.

Acetobacterium woodii, Alkalibaculum bacchii, Blautia producta,

Butyribacterium methylotrophicum, Clostridium aceticum, Clostridium autoethanogenum,

Clostridium carboxidivorans, Clostridium coskatii, Clostridium drakei, Clostridium formicoaceticum, Clostridium Ijungdahlii, Clostridium magnum, Clostridium ragsdalei,

Clostridium scatologenes, Eubacterium limosum, Moorella thermautotrophica, Moorella thermoacetica, Oxobacter pfennigii, Sporomusa ovata, Sporomusa silvacetica, Sporomusa sphaeroides or Thermoanaerobacter kiuvi.

In a preferred embodiment, the parent bacterium is Clostridium autoethanogenum, Clostridium Ijungdahlii, or Clostridium ragsdalei.

In a particularly preferred embodiment, the parent bacterium is Clostridium autoethanogenum.

In one embodiment, the invention relates to a non-naturally occurring WoodLjungdahl bacterium containing a heterologous thiolase and a disruptive mutation in one or more genes encoding, for example, one or more of NAD-dependent electron bifurcation [FeFe] hydrogenase, glutamate synthase, citramalate synthase, acetolactate decarboxylase, lactate dehydrogenase, acetate kinase, phosphate transacetylase and aldehyde dehydrogenase, the non-naturally occurring bacterium having increased carbon flux through acetoacetyl-CoA compared to the parent bacterium. In particular, the expression of one or more genes is reduced or eliminated compared to the parent bacterium.

In such an embodiment, the non-naturally occurring bacterium may produce a product, for example, acetone, isopropanol, 3-hydroxyisovaleryl-CoA, 3-hydroxyisovalerate, isobutylene, isopentenyl pyrophosphate, dimethylallyl pyrophosphate, isoprene, farnesene, 3-hydroxybutyryl-CoA, crotonyl CoA, 3-hydroxybutyrate , 3-hydroxybutyrylaldehyde, 1,3-butanediol, 2-hydroxyisobutyryl-CoA, 2hydroxyisobutyrate, butyryl-CoA, butyrate, butanol, caproate, hexanol, octanoate, octanol, 1,3hexanediol, 2-buten-1-ol, isovaleryl-CoA , isovalerate or isoamyl alcohol.

For example, if the parent bacterium is Clostridium autoethanogenum, (a) the NAD-dependent electron bifurcation [FeFeJ hydrogenase can be selected from the group consisting of CAETHG_1576, CAETHG_1578, CAETHG_3569, CAETHG_3570 and CAETHG_3571, (b); glutamate synthase can be selected

- 1 044153 from the group consisting of CAETHG_0477, CAETHG_1580, CAETHG_3850 and CAETHG_3851, (c) citramalate synthase may be CAETHG_2751, (d) acetolactate decarboxylase may be CAETHG_2932, (e) lactate dehydrogenase may be CAET HG_1147, (f) acetate kinase may be CAETHG_3359, (g) the phosphate transacetylase may be CAETHG_3358, or (h) the aldehyde dehydrogenase may be selected from the group consisting of CAETHG_1819, CAETHG_3287 and CAETHG_1830.

In yet another embodiment, the invention relates to a non-naturally occurring Wood-Ljungdahl bacterium containing a disruptive mutation in one or more genes, wherein the non-naturally occurring bacterium has increased carbon flux through chorismate compared to the parent bacterium.

Said one or more genes encode, for example, one or more of purine nucleoside phosphorylase, lactate permease, cystathionine gamma lyase, adenine phosphoribosyltransferase, 5'-nucleotidase/3'nucleotidase/exopolyphosphatase, mechanosensitive small conductance channel, arginine deiminase, apoenzyme LL-diaminopimelate aminotransferase and phosphopentomutase . In particular, the expression of one or more genes is reduced or eliminated compared to the parent bacterium.

In such an embodiment, the non-naturally occurring bacterium may produce a product such as chorismate, p-hydroxybenzoic acid, salicylate, 2-aminobenzoate, dihydroxybenzoate, 4-hydroxycyclohexanecarboxylic acid, and salts and ions thereof.

For example, if the parent bacterium is Clostridium Autoethanogenum, the indicated one or more genes can encode one or more from Caethg_0160, Caethg_0248, Caethg_0498, Caethg_1270, Caethg_1371, Caethg_2107, Caethg_30 21, Caethg_3510 and CAITHG_3924; if the parent bacterium is Clostridium ljungdahlii, said one or more genes may encode one or more of CLJU_c20750, CLJU_c21610, CLJU_c24380, CLJU_c33720, CLJU_c34740, CLJU_c42810, CLJU_c09270, CLJU_c14 280 and CLJU_c18150; and if the parent bacterium is Clostridium ragsdalei, said one or more genes may encode one or more of CLRAG_19250, CLRAG_31200, CLRAG_25120, CLRAG_24560, CLRAG_14800, CLRAG_25620, CLRAG_09600, or CLRAG_00520.

The present invention also provides a method for producing products by cultivating a microorganism according to the present invention in the presence of a substrate, for example, a gaseous substrate containing one or more CO, CO ₂ and/or H ₂ .

The term non-naturally occurring when applied to a microorganism is intended to mean that said microorganism carries at least one genetic modification not found in a naturally occurring strain of the specified species, including wild-type strains of the specified species of microorganism. Microorganisms not found in nature are usually developed in a laboratory or research facility.

The terms genetic modification, genetic alteration, or genetic engineering broadly refer to the manipulation of the genome or nucleic acids of a microorganism by human hands. Likewise, the terms genetically modified, genetically altered or genetically engineered refer to a microorganism containing such genetic modifications, genetic changes or genetically engineered elements. These terms can be used to differentiate a laboratory-derived microorganism from a naturally occurring microorganism. Genetic modification techniques include, for example, heterologous gene expression, gene or promoter insertion or deletion, nucleic acid mutation, altered gene expression or inactivation, enzyme engineering, directed evolution, knowledge-based design, random mutagenesis techniques, gene shuffling, and codon optimization.

Recombinant means that a nucleic acid, protein, or microorganism is the product of genetic modification, engineering, or recombination. In general, the term recombinant refers to a nucleic acid, protein, or microorganism that contains or is encoded by genetic material obtained from multiple sources, such as two or more different strains or species of microorganisms.

Wild type refers to the typical form of an organism, strain, gene, or characteristic as it occurs in nature, as opposed to mutant or variant forms.

Endogenous refers to a nucleic acid or protein that is present or expressed in a wild-type microorganism or the parent microorganism from which the microorganism of the present invention is derived. For example, an endogenous gene is a gene natively present in a wild-type microorganism or the parent microorganism from which the microorganism of the present invention is derived. In one embodiment, expression of an endogenous gene can be controlled by an exogenous regulatory element, such as an exogenous promoter.

Exogenous refers to a nucleic acid or protein whose origin is not related to the microorganism of the present invention. For example, an exogenous gene or enzyme can be created artificially or recombinantly and introduced into a microorganism according to the present invention

- 2 044153 or express it. An exogenous gene or enzyme can also be isolated from a heterologous microorganism and introduced into or expressed in the microorganism of the present invention. Exogenous nucleic acids can be adapted to be integrated into the genome of the microorganism of the present invention or to reside outside the chromosome of the microorganism of the present invention, for example, in a plasmid. Heterologous refers to a nucleic acid or protein derived from another strain or species and introduced into or expressed in a microorganism of the present invention.

The terms polynucleotide, nucleotide, nucleotide sequence, nucleic acid and oligonucleotide are used interchangeably. They refer to the polymeric form of nucleotides of any length, both deoxyribonucleotides and ribonucleotides or their analogues. Polynucleotides can have any three-dimensional structure and can have any function, known or unknown. The following are non-limiting examples of polynucleotides: coding or non-coding regions of a gene or gene fragment, loci (locus) determined by linkage analysis, exons, introns, messenger RNA (mRNA), transfer RNA, ribosomal RNA, short interfering RNA (siRNA), short hairpin RNA (shRNA), micro-RNA (miRNA), ribozymes, cDNA, recombinant polynucleotides, branched polynucleotides, plasmids, vectors, isolated DNA with any sequence, isolated RNA with any sequence, nucleotide probes and primers. The polynucleotide may contain one or more modified nucleotides, for example, methylated nucleotides or nucleotide analogues. Modifications to the nucleotide structure (if any) can be introduced before or after polymer assembly. The nucleotide sequence can be interrupted by non-nucleotide components. The polynucleotide can be further modified after polymerization, for example, by conjugation to a labeling moiety.

As used herein, the term expression refers to the process by which a polynucleotide is transcribed from a DNA template (eg, into mRNA or other RNA transcript) and/or the process by which the transcribed mRNA is subsequently translated into peptides, polypeptides, or proteins. Transcripts and encoded polypeptides may be collectively referred to as gene products.

The terms polypeptide, peptide and protein are used interchangeably herein to refer to amino acid polymers of any length. The polymer may be linear or branched, it may contain modified amino acids, and it may be interrupted by non-amino acid compounds. These terms also include modified amino acid polymer; for example, disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation or any other manipulation such as conjugation to a labeling moiety. As used herein, the term amino acid includes natural and/or non-naturally occurring or synthetic amino acids, including glycine and D- or L-optical isomers, as well as amino acid analogues and peptidomimetics.

Enzyme activity, or simply activity, broadly refers to enzymatic activity, including, but not limited to, enzyme activity, the amount of enzyme, or the availability of enzyme needed to catalyze a reaction. Accordingly, increasing enzyme activity includes increasing enzyme activity, increasing the amount of enzyme, or increasing the availability of an enzyme necessary to catalyze a reaction. Likewise, a decrease in enzyme activity includes a decrease in enzyme activity, a decrease in the amount of enzyme, or a decrease in the availability of an enzyme needed to catalyze a reaction.

Mutated refers to a nucleic acid or protein modified in a microorganism of the present invention compared to the wild-type microorganism or the parent microorganism from which the microorganism of the present invention is derived. In one embodiment, the mutation may be a deletion, insertion, or substitution in a gene encoding an enzyme. In yet another embodiment, the mutation may be a deletion, insertion, or substitution of one or more amino acids in the enzyme.

A disrupted gene refers to a gene that has been modified in some way to reduce or eliminate the expression of the gene, the regulatory activity of the gene, or the activity of the encoded protein or enzyme. The disorder may partially inactivate, completely inactivate, or delete a gene or enzyme. The disorder may be a knockout (KO) mutation that completely eliminates the expression or activity of a gene, protein, or enzyme. The disruption may also be a knockdown that reduces, but does not completely eliminate, the expression or activity of a gene, protein, or enzyme. A disruption can be any modification that reduces, prevents, or blocks the biosynthesis of a product produced by an enzyme. The disorder may include, for example, mutations in a gene encoding a protein or enzyme, mutations in a genetic regulatory element involved in the expression of a gene encoding an enzyme, introduction of a nucleic acid producing a protein that reduces or inhibits the activity of an enzyme, or introduction of a nucleic acid (eg, antisense RNA, RNAi, TALEN, siRNA, CRISPR or CRISPRi) or protein that inhibits the expression of a protein or enzyme. The violation can be introduced using any method

- 3 044153 ba, known in the art. For the purposes of the present invention, disruptions are performed in a laboratory and do not occur naturally.

Codon optimization refers to the mutation of a nucleic acid, such as a gene, for the purpose of optimized or improved translation of the nucleic acid in a particular strain or species of microorganisms. Codon optimization can result in increased translation speed or improved translation fidelity. In a preferred embodiment, the genes of the present invention are codon optimized for expression in Clostridium, in particular Clostridium autoethanogenum, Clostridium ljungdahlii or Clostridium ragsdalei. In a further preferred embodiment, the genes of the present invention are codon optimized for expression in Clostridium autoethanogenum LZ1561, deposited in the DSMZ under accession number DSM23693.

Overexpressed refers to an increase in the expression of a nucleic acid or protein in a microorganism of the present invention compared to the wild-type microorganism or the parent microorganism from which the microorganism of the present invention is derived. Overexpression can be achieved by any means known in the art, including altering the copy number of a gene, the rate of gene transcription, the rate of gene translation, or the rate of enzyme degradation.

The term variants includes nucleic acids and proteins whose sequence differs from the sequence of the reference nucleic acid and protein, for example, the sequence of the reference nucleic acid and protein described in the literature or exemplified herein. The present invention can be practiced using variant nucleic acids or proteins that perform substantially the same function as the reference nucleic acid or protein. For example, a variant protein may perform substantially the same function or catalyze substantially the same reaction as the reference protein. The variant gene may encode the same or substantially the same protein as the reference gene. The variant promoter may have substantially the same ability to stimulate expression of one or more genes as the reference promoter.

Such nucleic acids or proteins may be referred to herein as functionally equivalent variants. For example, functionally equivalent nucleic acid variants may include allelic variants, gene fragments, mutated genes, polymorphisms, and the like. Homologous genes from other microorganisms are also examples of functionally equivalent variants. These include homologous genes in species such as Clostridium acetobutylicum, Clostridium beijerinckii or Clostridium ljungdahlii, details of which are publicly available on websites such as Genbank or NCBI. Functionally equivalent variants also include nucleic acids whose sequence has been altered as a result of codon optimization for a particular microorganism. The functionally equivalent nucleic acid variant preferably has at least about 70%, about 80%, about 85%, about 90%, about 95%, about 98%, or greater nucleotide sequence identity (percent homology) to the reference nucleic acid. The functionally equivalent protein variant preferably has at least about 70%, about 80%, about 85%, about 90%, about 95%, about 98%, or greater amino acid sequence identity (percent homology) to the reference protein. The functional equivalence of a variant nucleic acid or protein can be assessed using any method known in the art.

Complementarity refers to the ability of a nucleic acid to form hydrogen bond(s) with another nucleic acid sequence in either the traditional Watson-Crick type or other non-traditional types. Percent complementarity indicates the percentage of residues in a nucleic acid molecule that can form hydrogen bonds (e.g., Watson-Crick base pairing) with a second nucleic acid sequence (e.g., 5, 6, 7, 8, 9, 10 out of 10 means 50, 60 , 70, 80, 90 and 100% complementarity). Perfectly complementary means that all adjacent residues in a nucleotide sequence form a hydrogen bond with the same number of adjacent residues in a second nucleotide sequence. Substantially complementary herein refers to a degree of complementarity of at least 60, 65, 70, 75, 80, 85, 90, 95, 97, 98, 99, or 100% in a region of 8, 9, 10, 11. 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 45, 50 or more nucleotides, or refers to two nucleic acids hybridizing in harsh conditions.

Hybridization refers to a reaction in which one or more polynucleotides form a complex that is stabilized by hydrogen bonds between the bases of the nucleotide residues. A hydrogen bond can be formed by Watson-Crick base pairing, Hoogsteen bonding, or any other sequence-specific method. The complex may contain two chains forming a double-stranded structure, three or more chains forming a multi-stranded complex, one self-hybridizing chain, or any of these.

- 4 044153 combination. The hybridization reaction may represent a step in a larger process, such as the initiation of PCR or the cleavage of a polynucleotide by an enzyme. A sequence that can hybridize with a given sequence is called the complementary strand of that sequence.

Nucleic acids can be delivered to the microorganism according to the present invention using any method known in the art. For example, nucleic acids can be delivered as uncoated nucleic acids or formulated with one or more agents, such as liposomes. Nucleic acids may be DNA, RNA, cDNA, or combinations thereof, depending on the situation. In certain embodiments, restriction inhibitors can be used. Additional vectors may include plasmids, viruses, bacteriophages, cosmids, and artificial chromosomes. In a preferred embodiment, nucleic acids are delivered to a microorganism according to the present invention using a plasmid. By way of example, transformation (including transduction or transfection) can be accomplished by electroporation, sonication, polyethylene glycol-mediated transformation, chemical or natural competence, protoplast transformation, prophage induction, or conjugation. In some embodiments, where active restriction enzyme systems are present, it may be necessary to methylate the nucleic acid before introducing the nucleic acid into the microorganism.

In addition, nucleic acids can be engineered to contain a regulatory element, such as a promoter, to enhance or otherwise control the expression of a particular nucleic acid. The promoter may be a constitutive promoter or an inducible promoter. Ideally, the promoter is a Wood-Ljungdahl pathway promoter, a ferredoxin promoter, a pyruvate:ferredoxin oxidoreductase promoter, an Rnf complex operon promoter, an ATP synthase operon promoter, or a phosphotransacetylase/acetate kinase operon promoter.

A microorganism is a microscopic organism, such as a bacterium, archaea, virus or fungus. The microorganism of the present invention is generally a bacterium. In the context of this invention, the term microorganism should be considered to include the term bacterium.

The parent microorganism is the microorganism used to obtain the microorganism according to the present invention. The parent microorganism may be a naturally occurring microorganism (ie, a wild-type microorganism) or a pre-modified microorganism (ie, a mutant or recombinant microorganism). The microorganism of the present invention can be modified to express or overexpress one or more enzymes not expressed or overexpressed in the parent microorganism. Likewise, a microorganism of the present invention can be modified to contain one or more genes not contained in the parent microorganism. The microorganism of the present invention can also be modified so that it does not express one or more enzymes expressed in the parent microorganism, or expresses them in smaller amounts. In one embodiment, the parent microorganism is Clostridium autoethanogenum, Clostridium ljungdahlii, or Clostridium ragsdalei. In a preferred embodiment, the parent microorganism is Clostridium autoethanogenum LZ1561, deposited on June 7, 2010 at the German Bank for Microorganisms and Cell Cultures (Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH, DSMZ), located at Inoffenstrasse 7B, D38124 Braunschweig, Germany, in accordance with the terms of the Budapest Treaty and assigned the registration number DSM23693. This strain is described in international patent application No. PCT/NZ2011/000144, published as WO 2012/015317.

The term derived from means that a nucleic acid, protein or microorganism is modified or adapted from another (eg, parent or wild type) nucleic acid, protein or microorganism to produce a new nucleic acid, protein or microorganism. Such modifications or adaptations typically include insertion, deletion, mutation or substitution of nucleic acids or genes. Typically, the microorganism of the present invention is derived from a parent microorganism. In one embodiment, the microorganism of the present invention is derived from Clostridium autoethanogenum, Clostridium ljungdahlii, or Clostridium ragsdalei. In a preferred embodiment, the microorganism of the present invention is derived from Clostridium autoethanogenum LZ1561, deposited in the DSMZ under accession number DSM23693.

The microorganism of the present invention can be further classified based on functional characteristics. For example, the microorganism of the present invention may be or may be derived from a C1-fixing microorganism, an anaerobic, acetogen, ethanologen, carboxydotroph and/or methanotroph. In table 1 shows a typical list of microorganisms and their functional characteristics.

- 5 044153

Table 1

WoodLjungdal's Path C1 - fixing microorganism Anaerobe Acetogen Ethanologen Autotroph Carboxydotroph Acetobacterium woodii + + + + +/- ¹ - - Alkalibaculum bacchii + + + + + + + Blautia producta + + + + - + + Butyribacterium methylotrophicum + + + + + + + Clostridium aceticum + + + + - + + Clostridium autoethanogenum + + + + + + + Clostridium carboxidivorans + + + + + + + Clostridium coskatii + + + + + + + Clostridium drakei + + + + - + + Clostridium formicoaceticum + + + + - + + Clostridium Ijungdahlii + + + + + + + Clostridium magnum + + + + - + m- ¹ Clostridium ragsdalei + + + + + + + Clostridium scatologenes + + + + - + + Eubacterium limosum + + + + - + + Moorella thermoautotrophica + + + + + + + Moorella thermoacetica (formerly Clostridium thermoaceticum) + + + + 3 + + Oxobacter pfennigii + + + + - + + Sporomusa ovata + + + + - + +/- ⁴ Sporomusa silvacetica + + + + - + +/- ⁵ Sporomusa sphaeroides + + + + - + +/- ^b Thermoanaerobacter kiuvi + + + + - + -

¹ Acetobacterium woodi can produce ethanol from fructose, but not from gas.

² The ability of Clostridium magnum to grow on CO has not been studied.

³ One strain of Moorella thermoacetica, Moorella sp., has been reported. HUC22-1, produces ethanol from gas.

⁴ The ability of Sporomusa ovata to grow on CO has not been studied.

⁵ The ability of Sporomusa silvacetica to grow on CO has not been studied.

⁶ The ability of Sporomusa sphaeroides to grow on CO has not been studied.

The Wood-Ljungdahl pathway refers to the Wood-Ljungdahl carbon fixation pathway described, for example, in the article Ragsdale, Biochim Biophys Acta, 1784: 1873-1898, 2008. The Wood-Ljungdahl microorganism, as expected, refers to a microorganism containing the Wood-Ljungdahl pathway. The microorganism of the present invention is a Wood-Ljungdahl microorganism, usually a Wood-Ljungdahl bacterium. Typically, the microorganism of the present invention contains the native Wood-Ljungdahl pathway. As used herein, the Wood-Ljungdahl pathway may be the native, unmodified Wood-Ljungdahl pathway or the Wood-Ljungdahl pathway with some degree of genetic modification (eg, overexpression, heterologous expression, knockout, etc.), provided that it can transform CO, CO ₂ and/or H ₂ in acetyl-CoA.

C1 refers to a molecule containing one carbon atom, such as CO, _CO2 , _CH4 or _CH3OH . C 1-oxygenate refers to a molecule containing one carbon atom that also contains at least one oxygen atom, such as CO, CO ₂ or CH ₃ OH. A C1 carbon source refers to a molecule containing one carbon atom that is the partial or sole carbon source for the microorganism of the present invention. For example, the C1 carbon source may contain one or more compounds selected from CO, CO ₂ , CH ₄ , CH ₃ OH or CH ₂ O ₂ . The C1 carbon source preferably contains one or more compounds selected from CO and CO ₂ . A C1-fixing microorganism is a microorganism capable of producing one or more products from a C1 carbon source. Typically, the microorganism of the present invention is a C1-fixing bacterium. In a preferred embodiment, the microorganism according to the present invention is obtained from the C1-fixing microorganism shown in Table 1.

An anaerobe is a microorganism that does not require oxygen to grow. An anaerobe can react negatively or even die in the presence of oxygen above a certain threshold. However, some anaerobes are able to tolerate low levels of oxygen (eg, 0.000001-5% oxygen). Typically, the microorganism according to the present invention is

-6044153 is an anaerobe. In a preferred embodiment, the microorganism according to the present invention is derived from the anaerobes listed in table. 1.

An acetogen is a microorganism that produces or is capable of producing acetate (or acetic acid) as a product of anaerobic respiration. In general, acetogens are obligate anaerobic bacteria that use the Wood-Ljungdahl pathway as the main mechanism for energy conservation and the synthesis of acetyl-CoA and acetyl-CoA-derived products such as acetate (Ragsdale, Biochim Biophys Acta, 1784: 1873- 1898, 2008). Acetogens use the acetyl-CoA pathway as (1) a mechanism for the reductive synthesis of acetyl-CoA from CO ₂ , (2) a terminal electron-withdrawing energy-saving process, (3) a mechanism for CO2 fixation (assimilation) during cellular carbon synthesis (Drake, Acetogenic Prokaryotes , In: The Prokaryotes, ^3rd edition, p. 354, New York, NY, 2006). All naturally occurring acetogens are C1-fixing, anaerobic, autotrophic, and non-methanotrophic organisms. Typically, the microorganism of the present invention is an acetogen. In a preferred embodiment, the microorganism according to the present invention comes from the acetogen listed in table. 1.

An ethanologen is a microorganism that produces or is capable of producing ethanol. Typically, the microorganism of the present invention is an ethanologen. In a preferred embodiment, the microorganism according to the present invention is derived from the ethanol given in table. 1.

An autotroph is a microorganism that can grow in the absence of organic carbon. Instead, autotrophs use inorganic carbon sources such as CO and/or CO2. Generally, the microorganism of the present invention is an autotroph. In a preferred embodiment, the microorganism according to the present invention comes from the autotroph shown in table. 1.

A carboxydotroph is a microorganism capable of using CO as the sole source of carbon and energy. Typically, the microorganism of the present invention is a carboxydotroph. In a preferred embodiment, the microorganism according to the present invention comes from the carboxydotroph shown in table. 1.

A methanotroph is a microorganism capable of using methane as its sole source of carbon and energy. In certain embodiments, the microorganism of the present invention is a methanotroph or is derived from a methanotroph. In other embodiments, the microorganism of the present invention is not a methanotroph or is not derived from a methanotroph.

In a broader sense, the microorganism according to the present invention can be derived from a microorganism of any genus or species listed in table. 1. For example, the microorganism may be a member of a genus selected from the group consisting of Acetobacterium, Alkalibaculum, Blautia, Butyribacterium, Clostridium, Eubacterium, Moorella, Oxobacter, Sporomusa and Thermoanaerobacter. In particular, the microorganism may be derived from a parent bacterium selected from the group consisting of:

Acetobacterium woodii, Alkalibaculum bacchii, Blautia producta, Butyribacterium methylotrophicum, Clostridium aceticum, Clostridium autoethanogenum, Clostridium carb oxidiv orans, Clostridium coskatii, Clostridium drakei, Clostridium formicoaceticum, Clostridium Ijungdahlii, Clostridium magnum, Clostridium ragsdale i, Clostridium scatologenes, Eubacterium limosum, Moorella thermautotrophica, Moorella thermoacetica, Oxobacter pfennigii, Sporomusa ovata, Sporomusa silvacetica, Sporomusa sphaeroides and Thermoanaerobacter kiuvi.

In a preferred embodiment, the microorganism of the present invention is obtained from the clostridia cluster, including the species Clostridium autoethanogenum, Clostridium Ijungdahlii and Clostridium ragsdalei. Such species were first described and studied in Abrini, Arch Microbiol, 161: 345-351, 1994 (Clostridium autoethanogenum), Tanner, Int J System Bacteriol, 43: 232-236, 1993 (Clostridium ljungdahlii) and Huhnke, WO 2008/028055 (Clostridium ragsdalei).

These three species are characterized by significant similarities. Specifically, all of these species are C1-fixing, anaerobic, acetogenic, ethanogenic, and carboxidotrophic members of the genus Clostridium. Such species have similar genotypes and phenotypes, energy conservation methods and enzymatic metabolism. In addition, these species are united in a cluster in group I of clostridial rRNA homology, and their 16S rRNA DNA is more than 99% identical, the G+C content in DNA is about 22-30 mol.%, they are gram-positive, characterized by similar morphology and size (the size of logarithmically growing cells is in the range between 0.5-0.7x3-5 μm), are mesophilic (optimal growth is observed at a temperature of 30-37 ° C), characterized by similar pH ranges of approximately 4-7.5 (at optimal pH

- 7 044153 approximately 5.5-6), do not contain cytochromes and store energy through the Rnf complex. In addition, these species have been shown to reduce carboxylic acids to form the corresponding alcohols (Perez, Biotechnol Bioeng, 110:1066-1077, 2012). It is important to note that all such species also exhibit strong autotrophic growth on CO-containing gases, produce ethanol and acetate (or acetic acid) as major fermentation products, and under certain conditions produce small amounts of 2,3-butanediol and lactic acid.

However, these three types also have a number of differences. These species were isolated from different sources: Clostridium autoethanogenum from rabbit intestines, Clostridium ljungdahlii from poultry farm waste, and Clostridium ragsdalei from freshwater sediments. These species differ in their utilization of various carbohydrates (e.g., rhamnose, arabinose), acids (e.g., gluconate, citrate), amino acids (e.g., arginine, histidine), and other substrates (e.g., betaine, butanol). In addition, these species differ in their auxotrophy for certain vitamins (eg, thiamine, biotin). These species differ in the nucleotide and amino acid sequences of genes and proteins of the Wood-Ljungdahl pathway, although the general organization and number of such genes and proteins are found to be the same in all species (Kopke, Curr Opin Biotechnol, 22: 320-325, 2011).

Thus, in conclusion, it can be noted that many of the characteristics of Clostridium autoethanogenum, Clostridium ljungdahlii or Clostridium ragsdalei are not specific to this species, but represent fairly general characteristics for such a cluster of C1-fixing, anaerobic, acetogenic, ethanogenic and carboxydotrophic representatives of the genus Clostridium . However, since these species are actually different, genetic modification or manipulation of one of these species may not have the same effect when using another of these species. For example, there may be differences in growth, performance, or product production.

The microorganism of the present invention may also be derived from an isolate or mutant of Clostridium autoethanogenum, Clostridium ljungdahlii or Clostridium ragsdalei. Clostridium autoethanogenum isolates and mutants include JA1-1 (DSM10061) (Abrini, Arch Microbiol, 161: 345-351, 1994), LBS1560 (DSM19630) (WO 2009/064200) and LZ1561 (DSM23693) (WO 2012/01531 7).Isolates and Clostridium ljungdahlii mutants include ATCC 49587 (Tanner, Int J Syst Bacteriol, 43: 232-236, 1993), PETCT (DSM13528, ATCC 55383), ERI-2 (ATCC 55380) (US 5593886), C-01 (ATCC 55988 ) (US 6368819), 0-52 (ATCC 55989) (US 6368819) and OTA-1 (Tirado-Acevedo, Production of bioethanol from synthesis gas using Clostridium ljungdahlii, PhD thesis, North Carolina State University, 2010). Isolates and mutants Clostridium ragsdalei include PI 1 (ATCC BAA-622, ATCC PTA-7826) (WO 2008/028055).

Substrate refers to a source of carbon and/or energy for a microorganism according to the present invention. Typically the substrate is gaseous and contains a source of C1 carbon, such as CO, CO ₂ and/or CH4. The substrate preferably contains a source of C1-carbon in the form of CO or CO+CO ₂ . The substrate may additionally contain other non-carbon components, for example, H ₂ , N ₂ or electrons.

In general, the substrate contains at least some amount of CO, such as about 1, 2, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 mole percent CO. The substrate may contain CO in the range of, for example, about 20-80, 30-70 or 40-60 mol.% CO. Preferably, the substrate contains about 40-70 mol.% CO (for example, steel mill gas or blast furnace gas), about 20-30 mol.% CO (for example, converter furnace gas), or about 15-45 mol.% CO (for example, synthesis gas). In some embodiments, the substrate may contain a relatively low amount of CO, such as about 1-10 or 1-20 mol% CO. The microorganism of the present invention typically converts at least a portion of the CO in the substrate into a product. In some embodiments, the substrate contains no or substantially no (<1 mol %) CO.

The substrate may contain some H2. For example, the substrate may contain about 1, 2, 5, 10, 15, 20 or 30 mol% H ₂ . In some embodiments, the substrate may contain a relatively high amount of H ₂ , such as about 60, 70, 80, or 90 mole percent H ₂ . In further embodiments, the substrate contains no or substantially no (<1 mol%) H ₂ .

The substrate may contain some CO ₂ . For example, the substrate may contain about 1-80 or 1-30 mol.% CO ₂ . In some embodiments, the substrate may contain less than about 20, 15, 10, or 5 mole percent CO ₂ . In yet another embodiment, the substrate contains little or no (<1 mol%) CO ₂ .

Although the substrate is typically gaseous, it may also be present in alternative forms. For example, the substrate can be dissolved in a liquid saturated with CO-containing gas using a microbubble dispersion generator. As a further example, the substrate can be adsorbed onto a solid support.

The substrate and/or source of C1-carbon may be a waste gas obtained as a by-product of an industrial process or from some other source, such as automobile exhaust or biomass gasification. In certain embodiments, the industrial process is selected from the group consisting of: ferrous metallurgy, e.g., steel production, non-ferrous metallurgy, oil refining, coal gasification, electrical power generation

- 8 044153 gie, pure carbon production, ammonia production, methanol production and coke production. In such embodiments, the substrate and/or C1 carbon source can be collected in an industrial process before being released into the atmosphere using any convenient method.

The substrate and/or source of C1-carbon may be a synthesis gas, for example, synthesis gas obtained from the gasification of coal or from petroleum residues, the gasification of biomass or lignocellulosic material, or from the reforming of natural gas. In yet another embodiment, the synthesis gas can be produced by gasifying municipal solid waste or industrial solid waste.

Substrate composition can have a significant impact on the efficiency and/or cost of the reaction. For example, the presence of oxygen (O2) can reduce the efficiency of the anaerobic fermentation process. Depending on the composition of the substrate, it may be desirable to treat, purify, or filter the substrate to remove undesirable contaminants, such as toxins, unwanted components, or dust particles, and/or to increase the concentration of desired components.

In some embodiments, the fermentation is performed in the absence of carbohydrate substrates, such as sugar, starch, lignin, cellulose, or hemicellulose.

The microorganism of the present invention can be cultured to produce one or more products. Thus, for example, the microorganism according to the present invention can produce or can be genetically engineered to produce ethanol (WO 2007/117157), acetate (WO 2007/117157), butanol (WO 2008/115080 and WO 2012/053905), butyrate (WO 2008 /115080), 2,3-butanediol (WO 2009/151342 and WO 2016/094334), lactate (WO 2011/112103), butene (wO 2012/024522), butadiene (WO 2012/024522), methyl ethyl ketone (2-butanone ) (WO 2012/024522 and WO 2013/185123), ethylene (WO 2012/026833), acetone (WO 2012/115527), isopropanol (WO 2012/115527), lipids (WO 2013/036147), 3-hydroxypropionate (3 -HP) (WO 2013/180581), isoprene (WO 2013/180584), fatty acids (WO 2013/191567), 2-butanol (WO 2013/185123), 1,2-propanediol (WO 2014/0369152), 1 -propanol (WO 2014/0369152), products derived from chorismate (WO 2016/191625), 3-hydroxybutyrate (WO 2017/066498) and 1,3-butanediol (WO 2017/0066498). In addition to one or more target products, the microorganism of the present invention can also produce ethanol, acetate and/or 2,3-butanediol. In certain embodiments, the microbial biomass itself may be considered a product.

A native product is a product produced by a non-genetically modified microorganism. For example, ethanol, acetate, and 2,3-butanediol are native products of Clostridium autoethanogenum, Clostridium ljungdahlii, and Clostridium ragsdalei. A non-native product is a product produced by a genetically modified microorganism, but not produced by the non-genetically modified microorganism from which the genetically modified microorganism is derived.

As used herein, reference to an acid (eg acetic acid or 2hydroxyisobutyric acid) shall also include the corresponding salt (eg acetate or 2hydroxyisobutyrate).

Selectivity refers to the ratio of the production of the target product to the production of all fermentation products produced by the microorganism. The microorganism of the present invention can be engineered to produce products with certain selectivity or minimal selectivity. In one embodiment, the target product represents at least about 5, 10, 15, 20, 30, 50, or 75% of the total fermentation products produced by the microorganism of the present invention. In one embodiment, the target product constitutes at least 10% of the total fermentation products produced by the microorganism of the present invention, such that the microorganism of the present invention has at least 10% selectivity for the target product. In yet another embodiment, the target product constitutes at least 30% of the total fermentation products produced by the microorganism of the present invention, such that the microorganism of the present invention has at least 30% selectivity for the target product.

Increased efficiency, increased efficiency, etc. terms include, but are not limited to, increasing growth rate, rate or volume of production, volume of product per volume of substrate consumed, or product selectivity. Efficiency can be measured relative to the performance of the parent microorganism from which the microorganism of the present invention is derived.

Typically, cultivation is performed in a bioreactor. The term bioreactor includes a culture/fermentation device consisting of one or more vessels, columns or piping, such as a continuous stirred reactor (CSTR), an immobilized cell reactor (ICR), a trickle-bed reactor (TBR), a bubble column, gas lift fermenter, static mixer or other vessel or other device suitable for bringing gas into contact with liquid. In some embodiments, the bioreactor may comprise a first growth reactor and a second culture/fermentation reactor. Substrate can be

- 9 044153 injected into one or both of such reactors. Throughout this document, the terms cultivation and fermentation are used interchangeably. These terms include both the growth phase and the biosynthesis phase of the product during the cultivation/fermentation process.

Cultivation is typically maintained in an aqueous culture medium containing nutrients, vitamins and/or minerals sufficient to support growth of the microorganism. The aqueous culture medium is preferably a medium for the growth of anaerobic microorganisms, for example, a minimal medium for the growth of anaerobic microorganisms. Suitable media are well known in the art.

To obtain the target product, cultivation/fermentation is preferably carried out under appropriate conditions. Typically, cultivation/fermentation is performed under anaerobic conditions. Reaction conditions to consider include pressure (or partial pressure), temperature, gas flow rate, liquid flow rate, pH of the medium, redox potential of the medium, stirring speed (if using a continuous mechanically stirred reactor), inoculum level, maximum concentrations of the gaseous substrate so that the gas content in the liquid phase does not become limiting, and maximum product concentrations to avoid inhibition of production. In particular, the rate of substrate introduction can be controlled to ensure that the gas concentration in the liquid phase does not become a limiting factor, since under gas-limited conditions the crop can consume products.

Operating a bioreactor at elevated pressures makes it possible to increase the rate of gas mass transfer from the gas phase to the liquid phase. Accordingly, it is generally preferable to perform the cultivation/fermentation at pressures greater than atmospheric pressure. Additionally, since a given gas conversion rate is dependent in part on substrate retention time, and retention time determines the required bioreactor volume, the use of pressurized systems can significantly reduce the required bioreactor volume and therefore the capital cost of culture/fermentation equipment. This in turn means that maintaining bioreactors at elevated pressure rather than atmospheric pressure can reduce retention time, defined as the volume of liquid in the bioreactor divided by the incoming gas flow rate. Optimal reaction conditions depend in part on the specific microorganism used. However, in general, it is preferable to carry out fermentation at pressures greater than atmospheric pressure. In addition, since a given gas conversion rate depends in part on the substrate retention time, and achieving the required retention time in turn determines the required bioreactor volume, the use of pressurized systems can significantly reduce the required bioreactor volume and, therefore, the capital cost of equipment for fermentation.

In some embodiments, the fermentation is performed in the absence of light or in the presence of an amount of light insufficient to meet the energy needs of the photosynthetic microorganisms. In some embodiments, the microorganism of the present invention is a non-photosynthetic microorganism.

The target products can be isolated or purified from the fermentation medium by any method or combination of methods known in the art, including, for example, fractional distillation, evaporation, permeable membrane evaporation, gas stripping, phase separation and extractive fermentation, including, for example, liquid-liquid fermentation. liquid extraction. In some embodiments, the target products are isolated from the fermentation medium by continuously partially removing the media from the bioreactor, separating microbial cells from the media (typically by filtration), and recovering one or more target products from the media. Alcohols and/or acetone can be isolated, for example, by distillation. Acids can be isolated, for example, by adsorption on activated charcoal. The separated microbial cells are preferably returned to the bioreactor. The cell-free filtrate remaining after removal of the target products is also preferably returned to the bioreactor. Additional nutrients (such as B vitamins) can be added to the cell-free filtrate to replenish the media before it is returned to the bioreactor.

The microorganism of the present invention contains at least one disrupted gene. In some embodiments, the microorganism of the present invention contains more than one disrupted gene, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 75, 100 or 200 disrupted genes. For example, the disrupted gene can be selected from Table 2. Although typical accession numbers are given for C. autoethanogenum, C. ljungdahlii, and C. ragsdalei, homologues in other Wood-Ljungdahl microorganisms can be identified by one skilled in the art.

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table 2

Clostridium autoethanogenum Clostridium Ijungdahlii Clostridium ragsdalei # Name EU No. Gene(s) Gene(s) Gene(s) 1 Isopropyl malate synthase/homocitrate synthase/cy tramalate synthase 2.3.1.182 CAETHG_2751 CUU_c06610 CLRAG_18420 2 Apoprotein [NiFeJ-hydrogenase 1, large subunit CAETHG_0861 CUU_c28660 CLRAG_34740 3 Apoprotein [NiFeJ-hydrogenase 1, small subunit CAETHG_0862 CUU_c28670 CLRAG_34750 4 ribopotein-alanine-N-acetyltransferase CAETHG_1676 CUU_c38200 CLRAG_20660 5 1-(5-phosphoribosyl)-5-[(5- phosphoribosylamine)methylideneamine]imidazole- 4-carboxamide isomerase 5.3.1.16 CAETHG_3262 CUU_cll710 CLRAG_11830 6 1-acyl-5p-glycero-3-phosphate acyltransferase 2.3.1.51 CAETHG_1773 CUU_c39280 CLRAG_21490 7 1-acyl-5p-glycero-3-phosphate acyltransferase 2.3.1.51 CAETHG_275O CUU_c06600 CLRAG_18410 8 1-deoxy-O-xylulose-5phosphate reductoisomerase 1.1.1.267 CAETHG_3391 CUU_cl3080 CLRAG_10710 9 1-deoxy-O-xylulose-5-phosphate synthase 2.2.1.7, 2.2.1.1 CAETHG_3205 CUU_clll60 CLRAG_12300 10 1,2-diacylglycerol-3-alphaglucosyltransferase CAETHG_0046 CUU_cl9690 CLRAG_39450 eleven Alcohol dehydrogenase class IV 1.1.1.1, 1.1.1.72, 1.1.1.21, 1.1.1.2 CAETHG_1078 CUU_c30740 CLRAG_16180 12 alcohol dehydrogenase 1.1.1.1, 1.1.1.72, 1.1.1.21, 1.1.1.2 CAETHG_1500 CUU_c35930 CLRAG_06430 13 Alcohol dehydrogenase class IV 1.1.1.1, 1.1.1.72, 1.1.1.21, 1.1.1.2 CAETHG_3604 CUU_cl5000 CLRAG_24350 14 chaperonin GroES CAETHG_1573 CLJU_c37200 CLRAG_36640 15 16S rRNA(guanine527-N7)-methyltransferase CAETHG_2116 CUU_c42900 CLRAG_25710 16 HSP20 family protein CAETHG_2094, CAETHG_2095 CLJU_c42700, CUU_c42690 CLRAG_25500 17 2-C-methyl-O-erythritol-2,4-cyclodiphosphate synthase 4.6.1.12 CAETHG_2263 CUU_cO157O CLRAG_27230

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18 2-C-methyl-O-erythritol-4phosphate cytidylyltransferase 2.7.7.60 CAETHG_1969 CUU_c41280 CLRAG_23470 19 2-isopropylmalate synthase 2.3.3.13, 4.1.3.12 CAETHG_2999 CUU_c09050 CLRAG_13980 20 2-keto-3-deoxyphosphogluconate aldolase 4.1.2.14, 4.1.3.16, 4.1.1.3 CAETHG_3254 CUU_cll630 CLRAG_25070 21 2-phosphosulfolactate phosphatase CAETHG_2017 CUU_c41880 CLRAG_04990 22 2,3,4,5-tetrahydropyridine-2,6-dicarboxylate N-acetyltransferase 2.3.1.89 CAETHG_1357 CUU_c34610 CLRAG_14690 23 235-rRNA-t(2)A-2503-methyltransferase CAETHG_3342 CUU_cl2600 CLRAG_11200 24 3-dehydroquinate dehydratase 4.2.1.10 CAETHG_0871 CUU_c28760 CLRAG_34840 25 3-dehydroquinate synthase 4.2.3.4, 4.6.1.3 CAETHG_0908 CUU_c29160 CLRAG_35160 26 3-deoxy-O-arabinoheptulosonate-7phosphate synthase 2.5.1.54, 4.1.2.15 CAETHG_0910 CUU_c29180 CLRAG_35180 27 3-deoxy-O-arabinoheptulosonate-7phosphate synthase 2.5.1.54, 4.1.2.15 CAETHG_3578 CUU_cl4780 CLRAG_20330 28 3-hydroxyacyl-[6-acyl-transporter]-dehydratase 4.2.1.61, 4.2.1.58, 2.3.1.86, 4.2.1.59, 4.2.1.60, 2.3.1.85, 4.2.1.0 CAETHG_2043 CUU_c42130 CLRAG_05240 29 3-hydroxyacyl-CoA dehydrogenase 1.1.1.157 CAETHG_0420, CAETHG_1586 CUU_c37300, CUU_c23560 CLRAG_17610 thirty 3-isopropylmalate dehydratase, large subunit 4.2.1.33 CAETHG_3000 CUU_c09060 CLRAG_13970 31 3-isopropyl malate/(8)-2- methylmalate dehydratase, small subunit 4.2.1.33 CAETHG_3001 CLJU_cO9O7O CLRAG_13960 32 3-isopropylmalate dehydrogenase 1.1.1.85, CAETHG_1795, CAETHG_3002 CLJU_c39500, CUU_c09080 CLRAG_13950 33 3-oxoacyl-[acyl carrier protein group]-reductase 2.3.1.85, 2.3.1.86, 1.1.1.100, 1.1.1.0, CAETHG_1392, CAETHG_2046 CLJU_c42160, CUU_c34940 CLRAG_26180 34 3-oxoacyl-[acyl carrier protein group]-synthase II 2.3.1.0, 2.3.1.41, 2.3.1.180, 2.3.1.86, 2.3.1.38, 2.3.1.85, 2.3.1.179 CAETHG_2045 CUU_c42150 CLRAG_05260 35 3-oxoacyl-[acyl carrier protein group]-synthase-3 2.3.1.0, 2.3.1.41, 2.3.1.180, 2.3.1.86, 2.3.1.38, 2.3.1.85, 2.3.1.179 CAETHG_2050 CUU_c42190 CLRAG_05300 36 3-phosphoshikimate-1-carboxyvinyltransferase 2.5.1.19 CAETHG_0907 CUU_c29150 CLRAG_35150 37 5'-nucleotidase / 3'-nucleotidase / exopolyphosphatase 3.1.3.5 CAETHG_1371 CUU_c34740 CLRAG_14800 38 Small ribosomal subunit protein S10P CAETHG_1948 CUU_c41050 CLRAG_23240 39 Small ribosomal subunit protein S12P CAETHG_1952 CUU_c41090 CLRAG_23280 40 small ribosomal subunit protein S13 CAETHG_1923 CUU_c40800 CLRAG_22990 41 small ribosomal subunit protein S19 CAETHG_1943 CUU_c41000 CLRAG_23190 42 small ribosomal subunit protein S3 CAETHG_1941 CUU_c40980 CLRAG_23170 43 small ribosomal subunit protein S4 CAETHG_1921 CUU_c40780 CLRAG_22970

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44 small ribosomal subunit protein S5 CAETHG_1930 CUU_c40870 CLRAG_23060 45 Small ribosomal subunit protein S6P CAETHG_2105 CUU_c42790 CLRAG_25600 46 small ribosomal subunit protein S7 CAETHG_1951 CUU_c41080 CLRAG_23270 47 small ribosomal subunit protein S8 CAETHG_1933 CUU_c40900 CLRAG_23090 48 4-amino-4-deoxychorismate lyase 4.1.3.38 CAETHG_1508 CUU_c36000 CLRAG_06500 49 4-aminobutyrate aminotransferase/(S)-3- amino-2-methylpropionate transaminase 2.6.1.19 CAETHG_0129 CUU_c20470 CLRAG_19550 50 4-diphosphocytidyl-2-C-methyl-O-erythritol kinase 2.7.1.148 CAETHG_2316 CUU_c02110 CLRAG_27710 51 4-hydroxy-3-methylbut-2-en-1yldiphosphate synthase CAETHG_3393 CUU_cl3100 CLRAG_10690 52 4-hydroxy-3-methylbut-2enyldiphosphate reductase 1.17.1.2 CAETHG_0218 CUU_c21320 CLRAG_30880 53 4-hydroxythreonine-4-phosphate dehydrogenase 1.1.1.262 CAETHG_2447 CUU_cO385O CLRAG_28920 54 5- (carboxyamine)imidazole ribonucleotide mutase 4.1.1.21 CAETHG_2948 CUU_cO854O CLRAG_07950 55 5-formyltetra hydrofolate cycloligase 6.3.3.2 CAETHG_0286 CUU_c21900 CLRAG_31440 56 Region of activation of vitamin B12-dependent methionine synthase CAETHG_2959 CUU_cO865O CLRAG_07840 57 large ribosomal subunit protein L1 CAETHG_1958 CUU_c41150 CLRAG_23340 58 large ribosomal subunit protein L18 CAETHG_1931 CUU_c40880 CLRAG_23070 59 large ribosomal subunit protein L2 CAETHG_1944 CUU_c41010 CLRAG_23200 60 large ribosomal subunit protein L23 CAETHG_1945 CUU_c41020 CLRAG_23210 61 large ribosomal subunit protein L3 CAETHG_1947 CUU_c41040 CLRAG_23230 62 large ribosomal subunit protein L31 CAETHG_2328 CUU_c02230 CLRAG_27830 63 large ribosomal subunit protein L35 CAETHG_1345 CUU_c34450 CLRAG_14530 64 large ribosomal subunit protein L5 CAETHG_1935 CUU_c40920 CLRAG_23110 65 large ribosomal subunit protein L6 CAETHG_1932 CUU_c40890 CLRAG_23080 66 protein L7/L12 of the large ribosomal subunit CAETHG_1956 CUU_c41130 CLRAG_23320 67 6-phosphofructokinase 2.7.1.11, 2.7.1.145, 2.7.1.144, 2.7.1.56 CAETHG_0648, CAETHG_2439 CUU_c03250, CUU_c25790 CLRAG_18670 68 6,7-dimethyl-8-ribityllumazine synthase 2.5.1.9 CAETHG_0304 CUU_c22060 CLRAG_31580 69 chaperonin GroEL CAETHG_1572 CUU_c37190 CLRAG_36630 70 Subfamily B protein of proteins containing an ATP-binding cassette CAETHG_3619 CUU_cl5170 CLRAG_24180 71 acetaldehyde dehydrogenase 1.2.1.10 CAETHG_1819, CAETHG_3287 CUU_c39730, CUU_cll960 CLRAG_21980 72 acetaldehyde dehydrogenase / alcohol dehydrogenase 1.1.1.1, 1.1.1.72, 1.1.1.21, 1.1.1.2 CAETHG_3747, CAETHG_3748 CUU_cl6520, CUU_cl6510 CLRAG_33310 73 acetate kinase 2.7.2.1, 2.7.2.15 CAETHG_3359 CUU_cl2780 CLRAG_11030 74 acetolactate synthase-1/2/3, large subunit 2.2.1.6, 4.1.3.18 CAETHG_1740 CUU_c38920 CLRAG_21100 75 acetolactate synthase, large subunit 2.2.1.6, 4.1.1.1, 4.1.3.18, 1.2.4.1 CAETHG_0124 CUU_c20420 CLRAG_25870 76 acetolactate synthase, large subunit 2.2.1.6, 4.1.1.1, 4.1.3.18, 1.2.4.1 CAETHG_0406 CUU_c23420 CLRAG_01330 77 acetolactate synthase, small subunit 2.2.1.6, 4.1.1.1, 4.1.3.18, CAETHG_0125 CUU_c20430 CLRAG_25860

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1.2.4.1 78 acetyl-CoA carboxylase- carboxyltransferase, alpha subunit 6.4.1.2 CAETHG_2040 CUU_c42100 CLRAG_05210 79 acetyl-CoA carboxylase- carboxyltransferase, beta subunit 6.4.1.2 CAETHG_2041 CUU_c42110 CLRAG_05220 80 acetylornithine/N- succinyldiaminopimelate aminotransferase 2.6.1.11 CAETHG_0238 CUU_c21510 CLRAG_31070 81 aconitate hydratase CAETHG_0478 CUU_c24200 CLRAG_24890 82 ACT domain containing protein CAETHG_0917 CUU_c29240 CLRAG_35250 83 FMN-dependent NADH azoreductase CAETHG_0583 CUU_c25150 CLRAG_03490 84 Adenine deaminase CAETHG_0460 CUU_c23940 CLRAG_17220 85 Adenine deaminase 3.5.4.2 CAETHG_0681 CUU_c26120 CLRAG_04200 86 Adenine deaminase 3.5.4.2 CAETHG_0989 CUU_c29900 CLRAG_35900 87 adenine phosphoribosyltransferase 2.4.2.7, 2.4.2.8 CAETHG_1270 CUU_c33720 CLRAG_24560 88 adenosine deaminase 3.5.4.4 CAETHG_0825 CUU_c28280 CLRAG_34360 89 alpha-ribazole phosphatase CAETHG_1462 CUU_c35540 CLRAG_06070 90 adenosylcobinamide kinase/adenosylcobinamide phosphate guanylyl transfer for 2.7.7.62, 2.7.1.156 CAETHG_1460 CUU_c35520 CLRAG_06050 91 adenosylcobyric acid synthase (glutamine hydrolyzing) CAETHG_1130 CUU_c32020 CLRAG_02650 92 S-adenosylmethionine decarboxylase 4.1.1.50 CAETHG_0217 CUU_c21310 CLRAG_30870 93 Adenylate kinase 2.7.4.11, 2.7.4.3 CAETHG_1926 CUU_c40830 CLRAG_23020 94 adenylsuccinate lyase 4.3.2.2 CAETHG_3420 CUU_cl3370 CLRAG_10420 95 Adenylsuccinate synthetase 6.3.4.4 CAETHG_2059 CUU_c42350 CLRAG_05460 96 ADP-ribose pyrophosphatase 3.6.1.13 CAETHG_3214 CUU_cll240 CLRAG_12220 97 carbon monooxide dehydrogenase, small subunit 1.1.1.204, 1.17.1.4 CAETHG_0424 CUU_c23600 CLRAG_17570 98 carbon monooxide dehydrogenase, medium subunit 1.1.1.204, 1.17.1.4 CAETHG_0425 CUU_c23610 CLRAG_17560 99 agmatine deiminase 3.5.3.12 CAETHG_2074 CUU_c42490 CLRAG_09010 100 accessory gene regulator B CAETHG_0843 CUU_c28480, CUU_c27530 CLRAG_34560 101 alanine racemase 5.1.1.1 CAETHG_1140 CUU_c32120, CUU_cl2010, CUU_c40390 CLRAG_02750 102 alanyl-tRNA synthetase CAETHG_3297 CUU_cl2150 CLRAG_11650 103 Protein containing a cysteine-rich domain CAETHG_0470 CUU_c24120, CUU_c24040 CLRAG_17130 104 aldehyde oxidoreductase 2.3.1.169 CAETHG_0471 CLJU_c24050, CUU_c24130 CLRAG_17120 105 aldose-1-epimerase 5.1.3.3 CAETHG_2227 CUU_c01190 CLRAG_30230 106 Allophanate hydrolase, subunit 1 CAETHG_0130 CUU_c20480 CLRAG_19540 107 protein containing an uncharacterized biotin-dependent carboxylase domain 3.5.1.54 CAETHG_0131 CUU_c20490 CLRAG_19530 108 acetolactate decarboxylase 4.1.1.5 CAETHG_2932 CUU_cO838O CLRAG_08070 109 alpha-N-arabinofuranosidase 3.2.1.55 CAETHG_2233 CUU_cO124O CLRAG_30180 110 amidophosphoribosyltransferase 2.4.2.14 CAETHG_2950 CUU_cO856O CLRAG_07930 111 ATP-binding protein of the polar amino acid transport system CAETHG_2759 CUU_cO669O CLRAG_18490 112 ABC transporter membrane protein amino acids of the PAAT family CAETHG_1212, CAETHG_2758 CLJU_c06680, CUU_c33140 CLRAG_15160 113 substrate-binding protein-ABC amino acid transporter, PAAT family CAETHG_0569, CAETHG_2757 CLJU_c06670, CUU_c25010 CLRAG_17770

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114 substrate-binding protein-ABC amino acid transporter, PAAT family CAETHG_1211 CUU_c33130 CLRAG_15170 115 Amino acid transporter CAETHG_0009, CAETHG_3736 CLJU_cl9320, CUU_cl6420 CLRAG_33220 116 antiporter major amino acids/polyamines, APA family CAETHG_0058 CUU_cl9780 CLRAG_39360 117 carrier amino acids/polyamines/organic cations of the APC superfamily CAETHG_0165 CUU_c20800 CLRAG_19200 118 carrier amino acids/polyamines/organic cations of the APC superfamily CAETHG_0231, CAETHG_3020 CUU_c21450, CUU_c09260 CLRAG_31010 119 antiporter major amino acids/polyamines, APA family CAETHG_0407, CAETHG_0408 CLJU_c23440, CUU_c23430 CLRAG_01320 120 Amino acid transporter CAETHG_0483, CAETHG_2967 CLJU_c08730, CUU_c24250 CLRAG_24920 121 carrier amino acids/polyamines/organic cations of the APC superfamily CAETHG_0491 CUU_c24320 CLRAG_24990 122 carrier amino acids/polyamines/organic cations of the APC superfamily CAETHG_1802, CAETHG_2803 CUU_cO712O, CUU_c39570 CLRAG_21780 123 carrier amino acids/polyamines/organic cations of the APC superfamily CAETHG_2547, CAETHG_2548 CUU_c04760, CUU_cO475O CLRAG_38130 124 transporter of amino acids/polyamines/organic cations of the APC superfamily CAETHG_3898 CUU_cl7900 CLRAG_00730 125 para-aminobenzoate synthetase, component 1 2.6.1.85 CAETHG_1509 CUU_c36010 CLRAG_06510 126 aminomethyltransferase CAETHG_0476 CUU_c24180 CLRAG_24850 127 aminopeptidase CAETHG_3684 CUU_cl5760 CLRAG_32920 128 ammonium transporter CAETHG_2467 CUU_cO4O4O CLRAG_29120 129 anaerobic sulfite reductase, subunit A CAETHG_0442 CUU_c23770 CLRAG_17400 130 Dissimilatory sulfite reductase (desulfoviridine), alpha and beta subunits 1.8.7.1 CAETHG_1629 CUU_c37920 CLRAG_37310 131 anaerobic sulfite reductase, subunit B CAETHG_0441 CUU_c23760 CLRAG_17410 132 anaerobic sulfite reductase, subunit C CAETHG_0440 CUU_c23750 CLRAG_17420 133 carbon monoxide dehydrogenase, catalytic subunit 1.2.7.4 CAETHG_3005 CUU_c09110 CLRAG_13910 134 carbon monooxide dehydrogenase, iron- sulfur subunit CAETHG_3004 CUU_cO91OO CLRAG_13920 135 Pyridine nucleotide disulfide oxidoreductase CAETHG_3003 CUU_cO9O9O CLRAG_13930 136 anthranilate phosphoribosyltransferase 2.4.2.18 CAETHG_3703 CUU_cl6090 CLRAG_33060 137 anthranilate synthase, component 1 4.1.3.27 CAETHG_3701 CUU_cl6070 CLRAG_33040 138 para-aminobenzoate synthetase, component 2 2.6.1.85, 4.1.3.27 CAETHG_151O, CAETHG_3702 CLJU_cl6080, CUU_c36020 CLRAG_06520 139 regulatory anti-anti-sigma factor, SpollAA CAETHG_1295 CUU_c33970 CLRAG_14120 140 anti-sigma-28 factor, FlgM family CAETHG_3044 CLJU_c09490 CLRAG_13610 141 arginase 3.5.3.1 CAETHG_0290 CUU_c21930 CLRAG_31480 142 Arginine/lysine/ornithine decarboxylase 4.1.1.18, 4.1.1.19 CAETHG_2244 CUU_cO138O CLRAG_27040 143 argininosuccinate lyase 4.3.2.1 CAETHG_2762 CUU_cO671O CLRAG_18510 144 argininosuccinate synthase 6.3.4.5 CAETHG_2761 CUU_c06700 CLRAG_18500 145 arginyl-tRNA synthetase CAETHG_0257 CLJU_c21700 CLRAG_31290 146 arsenite transport ATPase CAETHG_3665 CUU_cl5660 CLRAG_32720 147 asparagine synthase (glutamine-hydrolyzing) 6.3.5.4 CAETHG_0753 CUU_c26720 CLRAG_08590 148 asparagine synthase (glutamine-hydrolyzing) 6.3.5.4 CAETHG_3879 CUU_cl7710 CLRAG_01020 149 asparaginyl-tRNA synthetase CAETHG_2033 CUU_c42030 CLRAG_05140

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150 aspartate aminotransferase 2.6.1.23, 2.6.1.1 CAETHG_0215 CUU_c21290 CLRAG_30850 151 aspartate aminotransferase 2.6.1.23, 2.6.1.1 CAETHG_3417 CUU_cl3340 CLRAG_10450 152 aspartate ammonia lyase 4.2.1.2, 4.3.1.1, 3.5.1.38 CAETHG_2062 CUU_c42370 CLRAG_05490 153 aspartate ammonia lyase 4.2.1.2, 4.3.1.1, 3.5.1.38 CAETHG_2479 CUU_c04170 CLRAG_26890 154 aspartate carbamoyltransferase 2.1.3.2 CAETHG_1481 CUU_c35730 CLRAG_06260 155 aspartate carbamoyltransferase, regulatory subunit 2.1.3.2 CAETHG_1480 CUU_c35720 CLRAG_06250 156 aspartate kinase CAETHG_1187 CUU_c32890 CLRAG_15440 157 aspartate kinase CAETHG_1690 CUU_c38320 CLRAG_20790 158 aspartate racemase CAETHG_0938 CUU_c29440 CLRAG_35430 159 aspartate semialdehyde dehydrogenase CAETHG_1353 CUU_c34570 CLRAG_14650 160 asparaginyl-tRNA synthetase CAETHG_2765 CUU_c06740 CLRAG_18540 161 aspartyl aminopeptidase CAETHG_2066 CUU_c42410 CLRAG_05550 162 aspartyl tRNA synthetase CAETHG_1264 CUU_c33660 CLRAG_24620 163 aspartyl/glutamyl-tRNA (Asn/Gln)- amidetransferase, subunit A CAETHG_1553 CUU_c36920 CLRAG_36450 164 aspartyl/glutamyl-tRNA (Asn/GIn)- amidetransferase, subunit B CAETHG_1552 CUU_c36910 CLRAG_36440 165 aspartyl/glutamyl-tRNA (Asn/GIn)- amidetransferase, subunit C CAETHG_1554 CUU_c36930 CLRAG_36460 166 ATP phosphoribosyltransferase 2.4.2.17 CAETHG_3258 CUU_cll670 CLRAG_11870 167 ATP phosphoribosyltransferase, regulatory subunit 2.4.2.17 CAETHG_3257 CUU_cll660 CLRAG_11880 168 H+-transporting F-type ATPase, subunit a 3.6.3.14 CAETHG_2343 CUU_c02370 CLRAG_27980 169 FO subcomplex of ATP synthase, subunit B 3.6.3.14 CAETHG_2345 CUU_c02390 CLRAG_28000 170 FO subcomplex of ATP synthase, subunit C 3.6.3.14 CAETHG_2344 CUU_cO238O CLRAG_27990 171 Fl-subcomplex of ATP synthase, alpha subunit 3.6.3.14 CAETHG_2347 CUU_cO241O CLRAG_28020 172 Fl-subcomplex of ATP synthase, beta subunit 3.6.3.14 CAETHG_2349 CUU_c02430 CLRAG_28040 173 Fl-subcomplex of ATP synthase, delta subunit 3.6.3.14 CAETHG_2346 CLJU_c02400 CLRAG_28010 174 ATP-dependent protease C1p, ATP-binding subunit C1pX CAETHG_1471 CUU_c35630 CLRAG_06160 175 ATP-dependent protease C1p, ATP-binding subunit C1pA CAETHG_0538 CUU_c24730 CLRAG_18090 176 ATP-dependent protease C1p, protease subunit CAETHG_1192, CAETHG_1472 CLJU_c35640, CUU_c32940 CLRAG_15390 177 DNA helicase-2 / ATP-dependent DNA helicase PcgA CAETHG_1559 CUU_c36980 CLRAG_36520 178 ATP-dependent DNA helicase RecG CAETHG_3351 CUU_cl2700 CLRAG_11110 179 ATP-dependent DNA helicase RecQ CAETHG_0594 CUU_c25260 CLRAG_03610 180 cell division protease FtsH CAETHG_1987 CUU_c41530 CLRAG_04660 181 ATP-dependent protease C1p, adapter protein CIpS CAETHG_0539 CUU_c24740 CLRAG_18080 182 ATP-dependent protease Lon CAETHG_2097 CUU_c42720 CLRAG_25530 183 Predicted ATP-dependent protease CAETHG_3140 CUU_cl0500 CLRAG_12870 184 ATP-dependent RNA helicase DbpA CAETHG_2474 CLJU_c04110 CLRAG_26940 185 DNA binding protein HU-beta CAETHG_1996 CUU_c41670 CLRAG_04800 186 peptide chain releasing factor 2 CAETHG_2365 CUU_c02640 CLRAG_28240

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187 translation initiation factor IF-2 CAETHG_3398 CUU_cl3150 CLRAG_10640 188 CubicO group peptidase, class C betalactamase family CAETHG_1431, CAETHG_2979 CUU_c08840, CUU_c35230 CLRAG_05740 189 phosphoribosylaminoimidazole carboxamide for miltransferase / IMP cyclohydrolase 3.5.4.10, 2.1.2.3 CAETHG_0319 CUU_c22210 CLRAG_31790 190 BirA family transcription regulator, biotin operon repressor/biotin[acetyl-CoA carboxylase] ligase 6.3.4.14 CAETHG_0747 CUU_c26660 CLRAG_08530 191 riboflavin kinase/FMN- adenylyltransferase 2.7.7.2, 2.7.1.26 CAETHG_3402 CUU_cl3190 CLRAG_10600 192 mannose-1-phosphate guanylyltransferase / Mannose-6-phosphate isomerase 2.7.7.22 CAETHG_2615, CAETHG_2637 CUU_c05540, CUU_c05310 CLRAG_38830 193 flagella biosynthesis protein FliR/FlhB CAETHG_3126 CUU_cl0360 CLRAG_13010 194 dihydroneopterinaldolase/2-amino-4hydroxy-6- hydroxymethyl dihydropteridine diphosphokinase A 4.1.2.25, 2.7.6.3 CAETHG_2732 CUU_c06370 CLRAG_30460 195 bifunctional UDP-N- acetylglucosamine pyrophosphorylase / glucosamine-1-phosphate-N-acetyltransferase 2.3.1.4, 2.7.7.23, 2.3.1.157 CAETHG_2007 CUU_c41780 CLRAG_04910 196 phosphoribosylaminoimidazole carboxamide for miltransferase / IMP cyclohydrolase 3.5.4.10, 2.1.2.3 CAETHG_2953 CUU_c08590 CLRAG_07900 197 tRNA nucleotidyl transferase (enzyme, adding SSA) CAETHG_3219 CUU_cll280 CLRAG_12170 198 Protein containing the C-terminal domain of biotin carboxylase CAETHG_0127 CUU_c20450 CLRAG_19570 199 acetyl-CoA carboxylase subunit biotin carboxylase 6.3.4.14 CAETHG_2042 CUU_c42120 CLRAG_05230 200 LIVCS family branched chain amino acid transporter CAETHG_3882 CUU_cl7740 CLRAG_00980 201 amino acid aminotransferase branched chain 2.6.1.67, 2.6.1.42, 2.6.1.6 CAETHG_3032 CUU_c09370 CLRAG_13730 202 carbamate kinase 1.3.99.1, 2.7.2.2 CAETHG_0445, CAETHG_3025 CUU_c23800, CUU_c09300 CLRAG_17370 203 carbamate kinase 2.7.2.2 CAETHG_2081 CUU_c42550 CLRAG_09000 204 carbamoylphosphate synthase, large subunit 6.3.5.5 CAETHG_0589, CAETHG_2510 CUU_c04410, CUU_c25210 CLRAG_03560 205 carbamoylphosphate synthase, small subunit 6.3.5.5 CAETHG_0590, CAETHG_2508 CUU_cO44OO, CUU_c25220 CLRAG_03570 206 ABC carbohydrate transporter of the CUT1 family, substrate binding protein CAETHG_1309 CUU_c34110 CLRAG_14260 207 ABC-carbohydrate transporter of the CUT1 family, substrate-binding protein CAETHG_1464 CUU_c35560 CLRAG_06090 208 multiple transport system carbohydrates, substrate-binding protein CAETHG_2301 CUU_cO198O CLRAG_27580 209 carbon monoxide dehydrogenase, catalytic subunit 1.2.7.4 CAETHG_3899 CUU_cl7910 CLRAG_00720 210 carbon starvation protein CAETHG_1590, CAETHG_1591 CUU_c37350, CUU_c37340 CLRAG_36780 211 carbon storage regulator, CsrA CAETHG_3064 CUU_c09690 CLRAG_13480 212 4-carboxymuconolactone decarboxylase 4.1.1.44 CAETHG_0634 CUU_c25650 CLRAG_03850 213 CDP-diacylglycerol glycerol-3-phosphate-3phosphatidyltransferase 2.7.8.5 CAETHG_3410 CUU_cl3270 CLRAG_10520 214 cell division protein FtsA CAETHG_3311 CUU_cl2290 CLRAG_11510 215 cell division protein FtsA CAETHG_3846 CUU_cl7330 CLRAG_29250 216 cell division protein FtsQ CAETHG_3151 CUU_cl0610 CLRAG_12730 217 cell division transport system permease protein CAETHG_2423 CUU_c03080 CLRAG_28690 218 cell division protein FtsZ CAETHG_3312 CUU_cl2300 CLRAG_11500

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219 ATP-dependent protease Clp, ATP-binding subunit ClpB CAETHG_2717 CUU_cO617O CLRAG_07450 220 sensor kinase CheA, two-component system, chemotaxis protein family CAETHG_3038 CUU_cO943O CLRAG_13670 221 chemotaxis protein MotA CAETHG_2251 CUU_cO145O CLRAG_27110 222 purine binding chemotaxis protein CheW CAETHG_3034 CUU_cO939O CLRAG_13710 223 Chemotaxis protein CheD CAETHG_3035 CLJU_c09400 CLRAG_13700 224 purine binding chemotaxis protein CheW CAETHG_3041 CUU_cO946O CLRAG_13640 225 Chemotaxis protein CheC CAETHG_3039 CLJU_c09440 CLRAG_13660 226 methyltransferase - chemotaxis protein CheR CAETHG_3037 CUU_cO942O CLRAG_13680 227 response regulator CheB, two-component system, chemotaxis protein family CAETHG_3036 CUU_cO941O CLRAG_13690 228 Chloramphenicol O-acetyltransferase type A CAETHG_0663 CUU_c25940 CLRAG_04080 229 chorismate mutase 4.2.1.91, 4.2.1.51 CAETHG_0905 CUU_c29130 CLRAG_35130 230 chorismate synthase 4.2.3.5 CAETHG_0906 CUU_c29140 CLRAG_35140 231 chromosome replication initiator protein DnaA CAETHG_2124 cuu_coooio CLRAG_25790 232 [citrate(pro-35)-lyase]-ligase 2.3.3.1 CAETHG_1898 CUU_c40550 CLRAG_22740 233 citrate lyase, gamma subunit (acyl group carrier protein) 2.3.3.1 CAETHG_1901, CAETHG_2481 CUU_c40580 CLRAG_22770 234 citrate lyase, alpha subunit/citrate CoAtransferase 2.3.3.1 CAETHG_1899, CAETHG_2483 CUU_c40560 CLRAG_22750 235 citrate lyase, beta subunit/citril CoAlyase 2.3.3.1 CAETHG_1900, CAETHG_2482 CUU_c40570 CLRAG_22760 236 CO-methylating acetyl-CoA synthase, corrinoid-containing iron-sulfur protein, precursor of the large subunit 2.3.1.169 CAETHG_1610 CUU_c37570 CLRAG_36980 237 CO-methylating acetyl-CoA synthase, corrinoid-containing iron-sulfur protein, small subunit precursor / acetylCoA decarbonylase / delta subunit synthase 2.3.1.169 CAETHG_1611 CUU_c37580 CLRAG_36990 238 CO-methylating acetyl-CoA synthase precursor/acetyl-CoA decarbonylase/synthase beta subunit 2.3.1.169 CAETHG_1608 CUU_c37550 CLRAG_36960 239 a,c-diamide adenosyltransferase cob(1)iric acid 2.5.1.17 CAETHG_111O CUU_c31820 CLRAG_02450 240 adenosylcobinamide phosphate synthase CAETHG_1129 CUU_c32010 CLRAG_02640 241 cobalamin 5'-phosphate synthase 2.7.8.26 CAETHG_1461 CUU_c35530 CLRAG_06060 242 cobalt-precorrin-3-C17-methyltransferase 2.1.1.131 CAETHG_1114 CUU_c31860 CLRAG_02490 243 cobalt-precorrin-4-C11-methyltransferase 2.1.1.133 CAETHG_1116 CUU_c31880 CLRAG_02510 244 cobalt-precorrin-5A-acetaldehyde lyase CAETHG_1115 CUU_c31870 CLRAG_02500 245 cobalt-precorrin-5B-C1-methyltransferase CAETHG_112O CUU_c31920 CLRAG_02550 246 cobalt-precorrin-6B-(C15)-methyltransferase 2.1.1.132 CAETHG_1118 CUU_c31900 CLRAG_02530 247 precorrin-8X-methylmutase/cobalt- precorrin-8-methylmutase 5.4.1.2 CAETHG_1121 CUU_c31930 CLRAG_02560 248 precorrin-6A/cobalt-precorrin-bA- reductase 1.3.1.54 CAETHG_1H2 CUU_c31840 CLRAG_02470 249 CobW/HurB/UreG, nucleotide binding domain CAETHG_0147 CUU_c20640 CLRAG_19340 250 family of DNA binding proteins cold shock CAETHG_0027, CAETHG_0035 CUU_cl9580, CUU_cl9500 CLRAG_39610 251 cinA inducing protein competence/damage CAETHG_177O CUU_c39260 CLRAG_21470 252 condensin, subunit of ScpA CAETHG_322O CUU_cll290 CLRAG_12160 253 segregation and condensation protein B CAETHG_3221 CUU_cll300 CLRAG_12150 254 condensin, Smc subunit CAETHG_3367 CUU_cl2850 CLRAG_10950

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255 Cu+-exporting ATPase CAETHG_0557 CUU_c24900 CLRAG_17880 256 16S rRNA(cytidine1402-2'-0)-methyltransferase CAETHG_2254 CUU_c01480 CLRAG_27140 257 CTP synthase 6.3.4.2 CAETHG_2325 CLJU_cO22OO CLRAG_27800 258 Cu-Zn family superoxide dismutase 1.15.1.1 CAETHG_0977 CUU_c29780 CLRAG_35780 259 cyanophycin synthetase CAETHG_2315 CLJU_cO21OO CLRAG_27700 260 cyanophycinase CAETHG_2314 CLJU_cO2O9O CLRAG_27690 261 Cellobiose phosphorylase CAETHG_1687 CUU_c38300 CLRAG_20770 262 cyclopropane fatty acid phospholipid synthase CAETHG_0840 CUU_c28420 CLRAG_34500 263 cystathionine gamma lyase CAETHG_0498 CUU_c24380 CLRAG_25120 264 cysteine desulfurase CAETHG_0833 CLJU_c28360 CLRAG_34440 265 Selenecysteine lyase/cysteine desulfurase CAETHG_1227 CUU_c33280 CLRAG_14980 266 protein of the cysteine desulfurase family CAETHG_1218 CUU_c33190 CLRAG_15070 267 cysteine synthase A CAETHG_0497 CUU_c24370 CLRAG_25110 268 cysteine synthase A 2.5.1.47, 2.5.1.65, 4.2.99.8 CAETHG_1776 CUU_c39310 CLRAG_21520 269 Cysteine synthase CAETHG_2922 CUU_c08270 CLRAG_08120 270 cysteinyl-tRNA synthetase CAETHG_0170 CUU_c20850 CLRAG_19150 271 cysteinyl-tRNA synthetase CAETHG_1968 CUU_c41270 CLRAG_23460 272 dCMP deaminase 3.5.4.12 CAETHG_2339 CLJU_cO233O CLRAG_27940 273 cytidine deaminase CAETHG_3921 CUU_cl8120 CLRAG_00540 274 cytidylate kinase 2.7.4.14, 2.7.1.48 CAETHG_0219 CUU_c21330 CLRAG_30890 275 cytosine deaminase 3.5.4.1 CAETHG_4058 CUU_cl9230 CLRAG_39840 276 D-3-phosphoglycerate dehydrogenase 1.1.1.95 CAETHG_2211 CUU_c00970 CLRAG_19610 277 0-alanine-0-alanine ligase 6.3.2.4 CAETHG_1139 CUU_c32110 CLRAG_02740 278 C-alanyl-O-alanine carboxypeptidase CAETHG_2836 CUU_c07440 CLRAG_32250 279 O-alanyl-O-alanine carboxypeptidase (penicillin binding protein 5/6) CAETHG_3218 CUU_cll270 CLRAG_12180 280 O-alanyl-O-alanine carboxypeptidase CAETHG_3425 CUU_cl3410 CLRAG_10380 281 O-alanyl-O-alanine carboxypeptidase CAETHG_3680 CUU_cl5720 CLRAG_32880 282 O-alanyl-O-alanine carboxypeptidase CAETHG_3224 CUU_cll330 CLRAG_12120 283 D-glucarate dehydratase 4.2.1.40 CAETHG_0817 CUU_c28130, CUU_c28170 CLRAG_09100 284 gD-glutamyl-meso-diaminopimelate peptidase CAETHG_2777 CUU_c06860 CLRAG_18700 285 dihydropyrimidinase CAETHG_0444 CUU_c23790 CLRAG_17380 286 O-serine/O-alanine/glycine: proton symporter of the AAT family CAETHG_2928 CUU_c08330 CLRAG_08080 287 xylose isomerase 5.3.1.5 CAETHG_3932 CUU_cl8240 CLRAG_00370 288 EDD domain-containing protein of the DegV family CAETHG_3256 CUU_cll650 CLRAG_11890 289 DNA-binding transcriptional regulator of the MerR family CAETHG_3906 CUU_cl7970 CLRAG_00660 290 deoxyribose phosphate aldolase CAETHG_3922 CUU_cl8130 CLRAG_00530 291 dUTP pyrophosphatase 3.6.1.19, 3.6.1.23 CAETHG_3104 CLJU_cl0140 CLRAG_13230 292 dephospho-CoA kinase 2.7.1.24 CAETHG_1258 CUU_c33600 CLRAG_24680 293 diacylglycerol kinase (ATP) 2.7.1.107 CAETHG_2904 CUU_c08090 CLRAG_08260 294 diaminohydroxyphosphoribosylaminopyrimide indeaminase / 5-amino-6-(5- phosphoribosylamino)uracil reductase 3.5.4.26, 1.1.1.193 CAETHG_0307 CUU_c22090 CLRAG_31610 295 diaminopimelate decarboxylase 4.1.1.20 CAETHG_1688 CUU_c38310 CLRAG_20780 296 diaminopimelate epimerase 5.1.1.7 CAETHG_3166 CUU_cl0760 CLRAG_12580

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297 diaminopropionate ammonia lyase CAETHG_0451 CUU_c23860 CLRAG_17310 298 diguanylate cyclase domain-containing protein (GGDEF) CAETHG_1216 CUU_c33170 CLRAG_15120 299 Dihydrodipicoline reductase 1.3.1.26 CAETHG_1351 CUU_c34550 CLRAG_14630 300 Dihydrodipicoline reductase 1.3.1.26 CAETHG_3914 CUU_cl8050 CLRAG_00600 301 4-hydroxytetrahydrodipicolinate synthase 4.2.1.52 CAETHG_0823 CUU_c28230 CLRAG_09180 302 4-hydroxytetrahydrodipicolinate synthase 4.2.1.52 CAETHG_1352, CAETHG_2498 CUU_c04300, CUU_c34560 CLRAG_14640 303 dihydrofolate reductase CAETHG_0509 CUU_c24490 CLRAG_30080 304 dihydrolipoamide dehydrogenase 1.8.1.4 CAETHG_1613 CUU_c37600 CLRAG_37010 305 dihydroorotase 3.5.2.3 CAETHG_1585 CUU_c37290 CLRAG_36730 306 dihydroorotate dehydrogenase (NAD+), catalytic subunit 1.3.3.1, 1.3.99.11 CAETHG_1477 CUU_c35690 CLRAG_06220 307 dihydroorotate dehydrogenase, electron- transport subunit 1.3.3.1, 1.3.99.11 CAETHG_1478 CUU_c35700 CLRAG_06230 308 dihydropteroate synthase 2.5.1.15 CAETHG_2729 CUU_cO634O CLRAG_30490 309 dihydropyrimidinase 3.5.2.2 CAETHG_1496 CUU_c35890 CLRAG_06390 310 Dihydropyrimidine dehydrogenase (NAD+), PgeA subunit 1.3.1.2 CAETHG_1494 CUU_c35870 CLRAG_06370 311 dihydroxy acid dehydratase 4.2.1.9 CAETHG_0123 CUU_c20410 CLRAG_25880 312 16S rRNA(adenine1518-N6/adenine1519-N6) dimethyltransferase CAETHG_2279 CUU_cO177O CLRAG_27370 313 DNA gyrase, subunit A CAETHG_2130 CLJU_cOOO7O CLRAG_25850 314 topoisomerase-4, subunit A CAETHG_3014 CUU_cO92OO CLRAG_13830 315 DNA gyrase, subunit B CAETHG_2129 CUU_c00060 CLRAG_25840 316 DNA helicase/exodeoxyribonuclease V, subunit A CAETHG_1215 CUU_c33160 CLRAG_15130 317 DNA helicase/exodeoxyribonuclease V, subunit B CAETHG_2788 CUU_cO698O CLRAG_18820 318 DNA ligase (NAD+) CAETHG_1558 CUU_c36970 CLRAG_36510 319 DNA mismatch repair protein MutS2 CAETHG_1338 CUU_c34380 CLRAG_14460 320 DNA mismatch repair protein MutL CAETHG_0209 CUU_c21230 CLRAG_30810 321 DNA mismatch repair protein MutS CAETHG_0210 CUU_c21240 CLRAG_30820 322 DNA polymerase 1 CAETHG_1259 CUU_c33610 CLRAG_24670 323 DNA polymerase 3, alpha subunit CAETHG_2438 CUU_c03240 CLRAG_28840 324 DNA polymerase 3, alpha subunit CAETHG_1073 CUU_c30690 CLRAG_16120 325 DNA polymerase 3 beta subunit CAETHG_2125 CUU_c00020 CLRAG_25800 326 DNA polymerase 3, gamma/tau subunit CAETHG_2199 CUU_cOO85O CLRAG_19730 327 DNA polymerase III, delta subunit CAETHG_2882 CUU_cO789O CLRAG_25370 328 DNA polymerase 4 CAETHG_0189 CUU_c21040 CLRAG_18980 329 DNA polymerase 3, delta' subunit CAETHG_2247 CUU_cO141O CLRAG_27070 330 DNA primase CAETHG_2916 CUU_cO821O CLRAG_08180 331 DNA repair protein RadA/Sms CAETHG_1973 CLJU_c41320 CLRAG_23510 332 DNA replication and repair protein RadC CAETHG_2813 CUU_cO721O CLRAG_26630 333 DNA replication and repair protein RecF CAETHG_2127 CUU_cOOO4O CLRAG_25820 334 DNA replication and repair protein RecN CAETHG_3209 CUU_cll200 CLRAG_12260 335 DNA replication and repair protein RecO CAETHG_2906 CUU_cO811O CLRAG_08240 336 DNA replication and repair protein RecR CAETHG_2201 CUU_cOO87O CLRAG_19710 337 DNA topoisomerase-3 CAETHG_0360 CUU_c22980 CLRAG_01800 338 DNA topoisomerase-3 CAETHG_0411 CUU_c23470 CLRAG_17640 339 DNA topoisomerase-1 CAETHG_3383 CUU_cl3000 CLRAG_10790

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340 topoisomerase-4, subunit B CAETHG_3013 CUU_c09190 CLRAG_13840 341 DNA segregation ATPase FtsK/SpollE, S-DNA-T family CAETHG_3408 CUU_cl3250 CLRAG_10540 342 endonuclease-3 CAETHG_1771 CUU_c39270 CLRAG_21480 343 DNA-dependent RNA polymerase, alpha subunit CAETHG_1920 CUU_c40770 CLRAG_22960 344 DNA-dependent RNA polymerase, beta subunit CAETHG_1955 CUU_c41120 CLRAG_23310 345 DNA-dependent RNA polymerase, beta'- subunit CAETHG_1954 CUU_c41110 CLRAG_23300 346 DNA-dependent RNA polymerase, omega subunit CAETHG_3335 CUU_cl2530 CLRAG_11270 347 dTDP-4-dehydrorhamnose-3,5-epimerase 5.1.3.13 CAETHG_2619, CAETHG_2641 CLJU_cO535O, CUU_cO558O CLRAG_06720 348 dTDP-4-dehydrorhamnose reductase 1.1.1.133, CAETHG_2618, CAETHG_2640 CLJU_cO557O, CUU_cO534O CLRAG_06710 349 dTDP-MOK030-4,6-dehydratase 4.2.1.46 CAETHG_2616, CAETHG_2638 CLJU_cO555O, CUU_cO532O CLRAG_06690 350 glucose-1-phosphate thymidylyltransferase 2.7.7.33, 2.7.7.24 CAETHG_2617, CAETHG_2639 CLJU_cO533O, CUU_cO556O CLRAG_06700 351 electron transport flavoprotein, apoprotein alpha subunit CAETHG_0116, CAETHG_3472 CUU_cl3890, CUU_c20340 CLRAG_25950 352 electron transport flavoprotein, apoprotein alpha subunit CAETHG_0245 CUU_c21580 CLRAG_31170 353 electron transport flavoprotein, apoprotein alpha subunit CAETHG_1785 CUU_c39400 CLRAG_21610 354 electron transport flavoprotein, beta subunit CAETHG_0115, CAETHG_3471 CUU_cl3880, CUU_c20330 CLRAG_25960 355 electron transport flavoprotein, beta subunit CAETHG_0246 CUU_c21590 CLRAG_31180 356 electron transport flavoprotein, beta subunit CAETHG_1786 CUU_c39410 CLRAG_21620 357 electron transport complex protein RnfA 1.18.1.3 CAETHG_3231 CLJU_cll400 CLRAG_12050 358 electron transport complex protein RnfD 1.18.1.3 CAETHG_3228 CLJU_cll370 CLRAG_12080 359 electron transport complex protein RnfE 1.18.1.3 CAETHG_3230 CUU_cll390 CLRAG_12060 360 elongation factor P CAETHG_3190 CUU_cll010 CLRAG_12450 361 elongation factor Ts CAETHG_3386 CUU_cl3030 CLRAG_10760 362 elongation factor Ti CAETHG_1949, CAETHG_1963 CLJU_c41200, CUU_c41060 CLRAG_23390 363 Endonuclease IV CAETHG_0108 CUU_c20270 CLRAG_26020 364 2-enoate reductase CAETHG_0983 CUU_c29840 CLRAG_35850 365 2,4-dienoyl-CoA reductase CAETHG_1079 CUU_c30750 CLRAG_16190 366 2-enoate reductase CAETHG_1247 CUU_c33480 CLRAG_32290 367 enolase 4.2.1.11 CAETHG_1756 CUU_c39110 CLRAG_21260 368 enoyl [acyl transfer protein] reductase II CAETHG_2049 CUU_c42180 CLRAG_05290 369 Alcohol dehydrogenase class IV 1.1.1.1, 1.1.1.72, 1.1.1.21, 1.1.1.2 CAETHG_1813 CUU_c39670 CLRAG_21920 370 Alcohol dehydrogenase class IV 1.1.1.1, 1.1.1.72, 1.1.1.21, 1.1.1.2 CAETHG_3279 CUU_cll880 CLRAG_03030 371 ABC exinuclease, subunit A CAETHG_2427 CUU_cO312O CLRAG_28730 372 Exinuclease ABC, subunit B CAETHG_2426 CUU_c03110 CLRAG_28720 373 Exinuclease ABC, subunit C CAETHG_2432 CUU_cO317O CLRAG_28780 374 Exodeoxyribonuclease 1, subunit D CAETHG_0112 CUU_c20310 CLRAG_25980

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375 exodeoxyribonuclease V, alpha subunit CAETHG_2359 CUU_c02590 CLRAG_28190 376 Exodeoxyribonuclease VII, large subunit CAETHG_3202 CUU_clll30 CLRAG_12330 377 Exodeoxyribonuclease VII, small subunit CAETHG_3203 CUU_clll40 CLRAG_12320 378 Single-stranded DNA-specific exonuclease CAETHG_3018 CUU_c09240 CLRAG_13790 379 H+-transporting F-type ATPase, epsilon subunit 3.6.3.14 CAETHG_2350 CUU_cO244O CLRAG_28050 380 H+-transporting F-type ATPase, gamma subunit 3.6.3.14 CAETHG_2348 CUU_c02420 CLRAG_28030 381 ATP synthase protein 1 3.6.3.14 CAETHG_2342 CUU_c02360 CLRAG_27970 382 [FeFeJ-hydrogenase, group A 1.12.1.4, 1.1.99.33 CAETHG_2798, CAETHG_3841 CUU_cl7280, CLJU_c07070 CLRAG_18920 383 electron transport protein HydN CAETHG_0083, CAETHG_3840 CUU_c20030, CUU_cl7270 CLRAG_32510 384 ferrous iron transport protein A CAETHG_3480 CUU_cl3970 CLRAG_09280 385 protein containing a domain with a 4Fe4S dicluster CAETHG_2250 CUU_cO144O CLRAG_27100 386 ferredoxin CAETHG_2285 CLJU_c01820 CLRAG_27420 387 Fur family transcriptional regulator, ferric iron uptake regulator CAETHG_3301 CUU_cl2190 CLRAG_11610 388 ferritin CAETHG_0026 CUU_cl9490 CLRAG_39620 389 ferrous iron transporter protein B CAETHG_3481 CUU_cl3980 CLRAG_09290 390 ferrous iron transport protein A CAETHG_3479 CUU_cl3960 CLRAG_09270 391 flagella assembly protein FliH CAETHG_3114 CUU_cl0240 CLRAG_13130 392 Flagellar kinetosome rod protein FlgB CAETHG_3109 CUU_cl0190 CLRAG_13180 393 Flagellar kinetosome rod protein FlgG CAETHG_3134 CUU_cl0440 CLRAG_12930 394 Flagellar kinetosome rod protein FlgG CAETHG_3135 CUU_cl0450 CLRAG_12920 395 Flagellar kinetosome rod protein FlgC CAETHG_3110 CUU_cl0200 CLRAG_13170 396 flagellum protein FIU CAETHG_3116 CUU_cl0260 CLRAG_13110 397 flagellum biosynthesis protein FlhA CAETHG_3127 CUU_cl0370 CLRAG_13000 398 flagellum biosynthesis protein FlhF CAETHG_3128 CUU_clO38O CLRAG_12990 399 flagellum protein FliL CAETHG_3122 CUU_cl0320 CLRAG_13050 400 flagellum biosynthesis protein FliP CAETHG_3124 CUU_clO34O CLRAG_13030 401 flagellum biosynthesis protein FliQ CAETHG_3125 CUU_cl0350 CLRAG_13020 402 Flagellar hook associated protein 1 FlgK CAETHG_3046 CUU_c09510 CLRAG_13590 403 Flagellar hook associated protein 2 CAETHG_3056 CUU_c09610 CLRAG_13530 404 protein FliE of the flagellum hook-kinetosome complex CAETHG_3111 CUU_cl0210 CLRAG_13160 405 flagellum M-ring protein FliF CAETHG_3112 CLJU_clO22O CLRAG_13150 406 protein FliM flagellar motor switch CAETHG_3042 CUU_c09470 CLRAG_13630 407 flagellum motor switch protein FliG CAETHG_3113 CUU_clO23O CLRAG_13140 408 flagellum protein FliS CAETHG_3052 CUU_c09570 CLRAG_13540 409 flagellin CAETHG_3108 CUU_cl0180 CLRAG_13190 410 PrsA foldase protein CAETHG_2000 CUU_c41710 CLRAG_04840 411 dihydrofolate synthase / folylpolyglutamate synthase 6.3.2.12, 6.3.2.17 CAETHG_1365 CUU_c34680 CLRAG_14760 412 formate dehydrogenase, large subunit 1.2.1.43, 1.1.99.33 CAETHG_2790, CAETHG_2988 CLJU_c08930, CUU_c06990 CLRAG_18840 413 Formate tetrahydrofolate ligase 3.5.4.9, 6.3.4.3 CAETHG_1618 CUU_c37650 CLRAG_37060 414 forminotetra hydrofolate cyclodeaminase 4.3.1.4 CAETHG_1728 CUU_c38800 CLRAG_21060

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415 forminoglutamase 3.5.3.8 CAETHG_0228 CUU_c21420 CLRAG_30980 416 Formiminotetrahydrofolate cyclodeaminase 4.3.1.4 CAETHG_0230 CUU_c21440 CLRAG_31000 417 formylmethanofurandehydrogenase, subunit E CAETHG_2994 CLJU_c38060, CLJU_cO9OOO CLRAG_07510 418 Formiminotetrahydrofolate cyclodeaminase 3.5.4.9, 4.3.1.4, 6.3.4.3 CAETHG_1617 CUU_c37640 CLRAG_37050 419 formyltetrahydrofolate-dependent phosphoribosylglycinamide formyltransferase 2.1.2.2 CAETHG_2952 CUU_c08580 CLRAG_07910 420 1-phosphofructokinase 2.7.1.11, 2.7.1.145, 2.7.1.144, 2.7.1.56 CAETHG_0143 CUU_c20600 CLRAG_19380 421 fructose 1,6-bisphosphatase-3 3.1.3.11 CAETHG_0897 CUU_c29050 CLRAG_35050 422 probable phosphoglycerate mutase CAETHG_0464 CUU_c23980 CLRAG_17180 423 fructose bisphosphate aldolase class II 4.1.2.13 CAETHG_2184 CUU_c00660 CLRAG_19910 424 fructose bisphosphate aldolase 4.1.2.13 CAETHG_2382 CUU_cO281O CLRAG_28410 425 fumarase class 1, alpha subunit 4.2.1.81, 4.2.1.2, 4.2.1.32 CAETHG_1903 CLJU_c40600 CLRAG_22790 426 fumarate hydratase, beta subunit 4.2.1.81, 4.2.1.2, 4.2.1.32 CAETHG_1902 CUU_c40590 CLRAG_22780 427 2-keto-4-pentenoate hydratase/2oxohepta-3-ene-1,7-dioic acid hydratase (catechol pathway) CAETHG_0592 CUU_c25240 CLRAG_03590 428 gamma glutamyl transferase 2. Threonine peptidase. MEROPS, TOZ family 2.3.2.2, 3.4.11.4 CAETHG_4037 CUU_cl9030 CLRAG_40010 429 geranylgeranyl diphosphate synthase type II 2.5.1.29, 2.5.1.1, 2.5.1.10 CAETHG_3204 CUU_clll50 CLRAG_12310 430 protease spore CAETHG_2884 CUU_c07910 CLRAG_25390 431 diguanylate cyclase domain-containing protein (GGDEF) CAETHG_0847 CUU_c28520 CLRAG_34600 432 diguanylate cyclase domain-containing protein (GGDEF) CAETHG_0678 CUU_c26090 CLRAG_04180 433 gluconate permease GntP CAETHG_2180, CAETHG_3251 CUU_cll600, CUU_c00620 CLRAG_19960 434 uridine-5-modification enzyme carboxymethylaminomethyl-tRNA CAETHG_2117 CUU_c42910 CLRAG_25720 435 glucose-6-phosphate isomerase 5.3.1.9, 5.1.3.15 CAETHG_1568 CUU_c37130 CLRAG_36590 436 glutamate 5-kinase 2.7.2.11 CAETHG_2697 CUU_c05990 CLRAG_07220 437 glutamate formiminotransferase 2.1.2.5 CAETHG_0237 CUU_c21500 CLRAG_31060 438 conserved hypothetical protein CAETHG_1906 CUU_c40630 CLRAG_22820 439 Glutamate mutase, subunit E CAETHG_1905 CUU_c40620 CLRAG_22810 440 glutamate mutase, subunit S CAETHG_1907 CUU_c40640 CLRAG_22830 441 glutamate-N-acetyltransferase 2.3.1.1, 2.3.1.35 CAETHG_0240 CUU_c21530 CLRAG_31090 442 glutamate racemase 5.1.1.3 CAETHG_2023 CUU_c41940 CLRAG_05050 443 glutamate synthase (NADPH/NADH), small chain 1.4.1.13, 1.6.99.3 CAETHG_1580 CUU_c37240 CLRAG_36680 444 glutamate synthase (NADPH/NADH), large chain 1.4.1.13 CAETHG_3850 CUU_cl7370 CLRAG_29210 445 glutamate synthase (NADH), small subunit 1.4.1.13 CAETHG_3851 CUU_cl7380 CLRAG_29200 446 glutamate-1-semialdehyde-2,1-aminomutase 5.4.3.8 CAETHG_2521 CLJU_c04490 CLRAG_37850 447 glutamate-5-semialdehyde dehydrogenase 1.2.1.41 CAETHG_2698 CUU_c06000 CLRAG_07230 448 glutamine synthetase 6.3.1.2 CAETHG_2024 CUU_c41950 CLRAG_05060

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449 glucosaminefructose-6- phosphate aminotransferase (isomerizing) 2.6.1.16 CAETHG_1885 CLJU_c40420 CLRAG_22610 450 NAD+ synthase (glutamine hydrolyzing) 6.3.1.5, 6.3.5.1 CAETHG_2782 CUU_cO692O CLRAG_18760 451 glutaminyl-tRNA synthetase CAETHG_0755 CUU_c26740 CLRAG_08610 452 glutamyl-tRNA reductase 1.2.1.70 CAETHG_2520 CUU_c04480 CLRAG_37840 453 glutamyl-tRNA synthetase 6.1.1.17, 6.1.1.24 CAETHG_3423 CUU_cl3390 CLRAG_10400 454 Glutathionylspermidine synthase CAETHG_3949 CUU_cl8420 CLRAG_00260 455 glyceraldehyde-3-phosphate dehydrogenase (NAD+) 1.2.1.59, 1.2.1.12, 1.2.1.72 CAETHG_1760, CAETHG_3424 CUU_cl3400, CUU_c39150 CLRAG_21300 456 glycerol-3-phosphate dehydrogenase (NAD(P)+) 1.1.1.94, 1.1.1.261, 1.1.1.8 CAETHG_3330 CUU_cl2480 CLRAG_11320 457 glycero-3-phosphate dehydrogenase CAETHG_1600 CUU_c37480 CLRAG_36890 458 Protein family glycerophosphoryl diester phosphodiesterase CAETHG_0269 CUU_c21800 CLRAG_31340 459 glycine dehydrogenase (decarboxylating), alpha subunit CAETHG_0474 CUU_c24160 CLRAG_24830 460 glycine dehydrogenase subunit 2 CAETHG_0473 CUU_c24150 CLRAG_24820 461 glycyl-tRNA synthetase CAETHG_1981 CLJU_c41460 CLRAG_04590 462 GMP synthase (glutamine hydrolyzing) 6.3.5.2 CAETHG_1570 CUU_c37170 CLRAG_36610 463 GTP cyclohydrolase 1 3.5.4.16 CAETHG_2730 CUU_c06350 CLRAG_30480 464 GTP pyrophosphokinase 2.7.6.5 CAETHG_1269 CUU_c33710 CLRAG_24570 465 guanine deaminase CAETHG_0462 CUU_c23960 CLRAG_17200 466 guanylate kinase 2.7.4.8, 2.7.4.12 CAETHG_3334 CUU_cl2520 CLRAG_11280 467 molecular chaperone HtpG CAETHG_0057 CUU_cl9770 CLRAG_39370 468 heat-inducible transcriptional repressor HcA CAETHG_2889 CUU_c07960 CLRAG_25440 469 hemerythrin CAETHG_0273 CUU_c21830 CLRAG_31370 470 hemerythrin-like protein with a metal-binding domain CAETHG_1518 CUU_c36090 CLRAG_06600 471 hemolysin III CAETHG_1262 CUU_c33640 CLRAG_24640 472 heptaprenyl diphosphate synthase 2.5.1.29, 2.5.1.30, 2.5.1.33 CAETHG_3233 CUU_cll420 CLRAG_12030 473 histidine ammonia lyase 4.3.1.3 CAETHG_1182 CUU_c32840 CLRAG_15490 474 histidine ammonia lyase 4.3.1.3 CAETHG_0232 CUU_c21460 CLRAG_31020 475 histidinol dehydrogenase 1.1.1.23 CAETHG_3259 CUU_cll680 CLRAG_11860 476 histidinol phosphatase (PHP family) 3.1.3.15 CAETHG_3272 CUU_cll810 CLRAG_11730 477 histidinol phosphate aminotransferase 2.6.1.9, 2.6.1.58, 2.6.1.57, 2.6.1.5, 2.6.1.1 CAETHG_3263 CUU_cll720 CLRAG_11820 478 histidyl-tRNA synthetase CAETHG_1265 CUU_c33670 CLRAG_24610 479 Holliday structure DNA helicase, RuvA subunit CAETHG_1281 CUU_c33830 CLRAG_24450 480 Holliday structure DNA helicase, RuvB subunit CAETHG_1280 CUU_c33820 CLRAG_24460 481 holo-[acyl transfer protein] synthase 2.7.8.7 CAETHG_2415 CUU_c03000 CLRAG_28610 482 homocitrate synthase NifV 4.1.3.21, 2.3.3.14 CAETHG_2575 CUU_c04980 CLRAG_38370 483 homocitrate synthase NifV CAETHG_2574 CUU_c04970 CLRAG_38360

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484 cysteine desulfurase 4.1.99.1, 4.4.1.8, 4.4.1.1 CAETHG_0403, CAETHG_3293 CLJU_cl2110, CUU_c23390 CLRAG_01360 485 homoserine dehydrogenase 1.1.1.3 CAETHG_2807 CUU_c07150 CLRAG_26690 486 homoserine dehydrogenase 1.1.1.3 CAETHG_3099 CLJU_clOO9O CLRAG_13280 487 homoserine kinase 2.7.1.39 CAETHG_2808 CUU_c07160 CLRAG_26680 488 homoserine O-succinyltransferase CAETHG_0492 CUU_c24330 CLRAG_25000 489 Hpr(5er)-kinase/phosphatase CAETHG_0287 CUU_c21910 CLRAG_31450 490 Hydrogenase maturation protein NurS CAETHG_0371 CUU_c23080 CLRAG_01730 491 HypD hydrogenase maturation protein CAETHG_0370 CUU_c23070 CLRAG_01740 492 Hydrogenase maturation protein carbamoyl dehydratase NurE CAETHG_0369 CUU_c23060 CLRAG_01750 493 hydrogenase expression/formation protein NurE 2.7.4.16 CAETHG_1548 CUU_c36870 CLRAG_36400 494 Hydrogenase maturation protein carbamoyltransferase HypF CAETHG_0372 CUU_c23090 CLRAG_01720 495 cobyric acid a,c-diamide synthase 6.3.1,- CAETHG_1123 CUU_c31950 CLRAG_02580 496 hypothetical protein CAETHG_1730 CUU_c38820 CLRAG_08740 497 Uncharacterized conserved YgbK protein of the DUF1537 family CAETHG_2185 CLJU_c00670 CLRAG_19900 498 hydroxyethylthiazole kinase 2.7.1.50 CAETHG_1203 CUU_c33050 CLRAG_15280 499 hydroxyethylthiazole kinase 2.7.1.50 CAETHG_1415 CUU_c35060 CLRAG_26320 500 hydroxymethylbilane synthase 2.5.1.61, 4.3.1.8 CAETHG_1126 CUU_c31980 CLRAG_02610 501 glycerate dehydrogenase 1.1.1.95 CAETHG_0004, CAETHG_1243 CLJU_cl9280, CUU_c33430 CLRAG_39780 502 protein of unknown function (DUF4163) CAETHG_0010 CUU_cl9330 CLRAG_39760 503 NADPH-dependent FMN reductase CAETHG_0012 CUU_cl9350 CLRAG_39740 504 hypothetical protein CAETHG_0013 CUU_cl9360 CLRAG_39730 505 DNA-binding transcriptional regulator containing the XRE family HTH domain CAETHG_0015 CUU_cl9380 CLRAG_39710 506 hypothetical protein CAETHG_0016 CUU_cl9390 CLRAG_39700 507 rarD protein CAETHG_0020 CUU_cl9430 CLRAG_39680 508 protein of unknown function (DUF1848) CAETHG_0021 CUU_cl9440 CLRAG_39670 509 hypothetical protein CAETHG_0024 CUU_cl9470 CLRAG_39640 510 hypothetical protein CAETHG_0045 CUU_cl9680 CLRAG_39460 511 Hypothetical protein CAETHG_0050 CUU_cl9730 CLRAG_39410 512 Uncharacterized conserved protein containing a FIST_N domain CAETHG_0054 CUU_cl9750 CLRAG_39390 513 hypothetical protein CAETHG_0060 CUU_cl9800 CLRAG_39280 514 Ala-tRNA(Pro) deacylase CAETHG_0063 CLJU_cl9830 CLRAG_39250 515 L-cysteine desulfidase CAETHG_0067 CUU_cl9870 CLRAG_39210 516 hypothetical protein CAETHG_0074 CUU_cl9940 CLRAG_39120 517 hypothetical protein CAETHG_0075, CAETHG_2375 CLJU_cO273O, CUU_cl9950 CLRAG_39090 518 putative GTP pyrophosphokinase 2.7.6.5 CAETHG_0076, CAETHG_1066 CLJU_c30620, CUU_cl9960 CLRAG_39080 519 hypothetical protein CAETHG_0081, CAETHG_3842 CLJU_c20010, CUU_cl7290 CLRAG_29290 520 MOSC domain-containing protein CAETHG_0100, CAETHG_0572 CLJU_c20190, CUU_c25040 CLRAG_29730 521 protein of the excisionase family containing a DNA-binding domain CAETHG_0106 CUU_c20250 CLRAG_26040 522 transporter family protein CAETHG_0107 CUU_c20260 CLRAG_26030 523 hypothetical protein (DUF2334) CAETHG_0111 CUU_c20300 CLRAG_25990

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524 hypothetical protein CAETHG_0126, CAETHG_0858 CUU_c28630, CLJU_c20440 CLRAG_19580 525 Protein UPF0271 CAETHG_0133 CUU_c20510 CLRAG_19510 526 Protein of unknown function (DUF1097) CAETHG_0134 CUU_c20520 CLRAG_19500 527 Predicted metal-binding protein CAETHG_0136 CUU_c20540 CLRAG_19460 528 Protein of unknown function (DUF1638) CAETHG_0146 CUU_c20630 CLRAG_19350 529 hypothetical protein CAETHG_0148 CUU_c20650 CLRAG_19330 530 Predicted metal-binding protein CAETHG_0149 CUU_c20660 CLRAG_19320 531 protein of unknown function (DUF4445) CAETHG_0156 CUU_c20720 CLRAG_19280 532 hypothetical protein CAETHG_0167 CUU_c20820 CLRAG_19180 533 hypothetical protein CAETHG_0168 CUU_c20830 CLRAG_19170 534 Ion channel CAETHG_0171 CUU_c20860 CLRAG_19140 535 HutD protein CAETHG_0172 CUU_c20870 CLRAG_19130 536 Protein of unknown function (DUF1657) CAETHG_0174 CUU_c20890 CLRAG_19120 537 Uncharacterized membrane protein YcaP family DUF421 CAETHG_0175 CUU_c20900 CLRAG_19110 538 Protein of unknown function (DUF1657) CAETHG_0179 CUU_c20950 CLRAG_19070 539 Protein of unknown function (DUF3006) CAETHG_0181 CUU_c20970 CLRAG_19050 540 hypothetical protein CAETHG_0187 CUU_c21020 CLRAG_19000 541 Cis-tRNA(Pro) deacylase CAETHG_0201 CUU_c21150 CLRAG_30710 542 uroporphyrinogen decarboxylase CAETHG_0204 CUU_c21180 CLRAG_19410 543 Hemetrin-like domain-containing protein CAETHG_0243 CUU_c21560 CLRAG_31140 544 Nickel-dependent lactate racemase CAETHG_0247, CAETHG_2534 CLJU_c04620, CUU_c21600 CLRAG_31190 545 RNase_H superfamily protein CAETHG_0250 CUU_c21630 CLRAG_31220 546 Hydrolase TIGR01490 of the HAD superfamily, subfamily IB 3.1.3.3 CAETHG_0251 CUU_c21640 CLRAG_31230 547 Viral attachment protein, p12 family protein CAETHG_0254 CUU_c21670 CLRAG_31260 548 CBS domain-containing protein CAETHG_0255 CUU_c21680 CLRAG_31270 549 hypothetical protein CAETHG_0256 CUU_c21690 CLRAG_31280 550 putative membrane protein CAETHG_0265 CUU_c21770 CLRAG_31310 551 hypothetical protein CAETHG_0266 CUU_c21780 CLRAG_31320 552 Uncharacterized membrane protein YvID of the DUF360 family CAETHG_0274 CUU_c21840 CLRAG_31380 553 hypothetical protein CAETHG_0275 CUU_c21850 CLRAG_31390 554 protein of unknown function (DUF896) CAETHG_0288 CUU_c21920 CLRAG_31460 555 hypothetical protein CAETHG_0297 CUU_c21990 CLRAG_31520 556 hypothetical protein CAETHG_0299 CUU_c22010 CLRAG_31540 557 hypothetical protein CAETHG_0301 CUU_c22030 CLRAG_31560 558 Soluble P-type ATPase CAETHG_0317 CUU_c22190 CLRAG_31770 559 cobalt/nickel transport protein CAETHG_0320 CUU_c22220 CLRAG_31800 560 Xylose isomerase-like protein, containing a TIM barrel domain CAETHG_0322 CUU_c22240 CLRAG_31820 561 RND family efflux transporter, MFP subunit CAETHG_0324, CAETHG_2692 CLJU_cO595O, CUU_c22260 CLRAG_31840 562 PucR protein containing a C-terminal helix-loop-helix domain CAETHG_0338 CUU_c22760 CLRAG_02030 563 1_-2-Aminothiazoline-4-carboxylic acid hydrolase CAETHG_0343 CUU_c22810 CLRAG_01980 564 succinate dehydrogenase/fumarate reductase, iron-sulfur subunit 1.3.99.1 CAETHG_0344 CUU_c22820 CLRAG_01970 565 Uncharacterized SAM-binding CAETHG_0346 CUU_c22840 CLRAG_01950

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YcdF family protein DUF218 566 hypothetical protein CAETHG_0347 CUU_c22850 CLRAG_01940 567 3',5'-cAMP phosphodiesterase CpdA CAETHG_0348 CUU_c22860 CLRAG_01930 568 protein of unknown function (DUF326) CAETHG_0349 CUU_c22870 CLRAG_01920 569 CRISPR-associated protein Cshl CAETHG_0359 CUU_c22970 CLRAG_01810 570 Component of nitrogenase type 1, oxidoreductase CAETHG_0366 CUU_c23030 CLRAG_01780 571 Component of nitrogenase type 1, oxidoreductase CAETHG_0367 CUU_c23040 CLRAG_01770 572 Component of nitrogenase type 1, oxidoreductase CAETHG_0373 CUU_c23100 CLRAG_01710 573 Putative multidrug resistance efflux transporter CAETHG_0376 CUU_c23130 CLRAG_01680 574 hypothetical protein CAETHG_0380 CUU_c23170 CLRAG_01650 575 domain containing protein 3D (Asp-Asp-Asp) CAETHG_0383 CUU_c23200 CLRAG_01530 576 ABC-2 transport system permease protein CAETHG_0389 CUU_c23260 CLRAG_01470 577 protein of the Ca-activated chloride channel family CAETHG_0395 CUU_c23310 CLRAG_01430 578 hypothetical protein 2.1.1.45 CAETHG_0396 CUU_c23320 CLRAG_01420 579 hypothetical protein CAETHG_0404 CUU_c23400 CLRAG_01350 580 S component of the folate family transporter ECF CAETHG_0405 CUU_c23410 CLRAG_01340 581 Region of activation of vitamin B12-dependent methionine synthase CAETHG_0409 CUU_c23450 CLRAG_17660 582 hypothetical protein CAETHG_0428 CUU_c23640 CLRAG_17530 583 Protein of unknown function (DUF1116) CAETHG_0430 CUU_c23660 CLRAG_17510 584 Protein of unknown function (DUF2877) CAETHG_0432 CUU_c23680 CLRAG_17490 585 An uncharacterized protein of the pyridoxamine 5'-phosphate oxidase (PNPOx-) family like) CAETHG_0434, CAETHG_0487 CUU_c24290, CUU_c23700 CLRAG_17470 586 probable redox protein of the C_GCAxxG_C_C family CAETHG_0468 CLJU_c24090, CUU_c24020 CLRAG_30590 587 hypothetical protein CAETHG_0469 CLJU_c24110, CUU_c24030 CLRAG_17140 588 hypothetical protein 2.3.1.0, 2.3.1.86, 2.3.1.39, 2.3.1.3, 2.3.1.2, 2.3.1.1, 2.3.1.85 CAETHG_0488 CUU_c24300 CLRAG_24970 589 Regulator of protease activity HfIC of the stomatin/prohibitin superfamily CAETHG_0490 CUU_c24310 CLRAG_24980 590 epoxyqueuosine reductase CAETHG_0495 CUU_c24350 CLRAG_25090 591 hypothetical protein CAETHG_0500 CUU_c24400 CLRAG_25130 592 hypothetical protein CAETHG_0508 CUU_c24480 CLRAG_30090 593 Uncharacterized membrane protein CAETHG_0510 CUU_c24500 CLRAG_30070 594 N-terminal anti-sigma factor CAETHG_0512 CUU_c24520 CLRAG_30050 595 RNA polymerase sigma factor CAETHG_0513 CUU_c24530 CLRAG_30040 596 Drug/metabolite transporter (DMT) superfamily permease CAETHG_0533 CUU_c24680 CLRAG_18150 597 Protein containing a methyltransferase domain CAETHG_0535 CUU_c24700 CLRAG_35650 598 hypothetical protein CAETHG_0536 CUU_c24710 CLRAG_18110 599 Uncharacterized membrane protein CAETHG_0537 CUU_c24720 CLRAG_18100 600 Protein of unknown function (DUF2975) CAETHG_0546 CUU_c24810 CLRAG_17970

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601 hypothetical protein CAETHG_0550 CUU_c24830 CLRAG_17950 602 DNA-binding transcriptional regulator of the FrmR family CAETHG_0558 CUU_c24910 CLRAG_17870 603 WG-containing repeat protein CAETHG_0560 CUU_c24930 CLRAG_17850 604 integral membrane protein of the YjbE family CAETHG_0561 CUU_c24940 CLRAG_17840 605 EDD domain-containing protein of the DegV family CAETHG_0563 CUU_c24960 CLRAG_17820 606 PucR protein containing a C-terminal helix-loop-helix domain CAETHG_0568 CUU_c25000 CLRAG_17780 607 hypothetical protein CAETHG_0570 CUU_c25020 CLRAG_17760 608 hypothetical protein CAETHG_0575 CUU_c25070 CLRAG_17710 609 ABC-2 family transport protein CAETHG_0579 CUU_c25110 CLRAG_03450 610 hypothetical protein CAETHG_0582 CUU_c25140 CLRAG_03480 611 regulatory protein blaRl CAETHG_0585 CUU_c25170 CLRAG_03510 612 Putative protein containing amidase domain CAETHG_0586 CUU_c25180 CLRAG_03520 613 O-alanyl-O-alanine carboxypeptidase CAETHG_0587 CUU_c25190 CLRAG_03530 614 hypothetical protein CAETHG_0596 CUU_c25270 CLRAG_03620 615 hypothetical protein CAETHG_0597 CUU_c25280 CLRAG_03630 616 Uncharacterized membrane protein YczE CAETHG_0621 CUU_c25520 CLRAG_03730 617 hypothetical protein CAETHG_0622 CUU_c25530 CLRAG_03740 618 PAP2 superfamily protein CAETHG_0625 CUU_c25550 CLRAG_03750 619 C-terminal O-glucuronyl-C5 epimerase CAETHG_0628, CAETHG_0762 CUU_c25590, CUU_c26810 CLRAG_03790 620 Protein of the alpha/beta hydrolase family CAETHG_0630 CUU_c25610 CLRAG_03810 621 ABC-2 family transport protein CAETHG_0638 CUU_c25690 CLRAG_03890 622 ABC-2 family transport protein CAETHG_0639 CUU_c25700 CLRAG_03900 623 hypothetical protein CAETHG_0643 CUU_c25740 CLRAG_03970 624 ABC-2 family transport protein CAETHG_0657 CUU_c25880 CLRAG_04020 625 Putative zinc finger domain protein CAETHG_0659 CUU_c25900 CLRAG_04040 626 Uncharacterized conserved protein of the DUF2164 family CAETHG_0661 CUU_c25920 CLRAG_04060 627 Uncharacterized Yjbl protein containing pentapeptide repeats CAETHG_0662 CUU_c25930 CLRAG_04070 628 Protein of unknown function (DUF4003) CAETHG_0702 CUU_c26250 CLRAG_04370 629 hypothetical protein CAETHG_0714 CUU_c26330 CLRAG_04420 630 Conservative protein containing a Zn-ribbon-like motif, possibly RNA-binding CAETHG_0715 CUU_c26340 CLRAG_04430 631 Sulfite Exporter TauE/SafE CAETHG_0723 CUU_c26420 CLRAG_04510 632 Protein containing a 4Pe-45-binding domain CAETHG_0724 CUU_c26430 CLRAG_04520 633 hypothetical protein CAETHG_0725 CUU_c26440 CLRAG_04530 634 hypothetical protein CAETHG_0726 CUU_c26450 CLRAG_04540 635 hypothetical protein CAETHG_0731 CUU_c26500 CLRAG_08380 636 hypothetical protein CAETHG_0737 CUU_c26560 CLRAG_08440 637 photoproduct lyase spores 4.1.99,- CAETHG_0740 CUU_c26590 CLRAG_08460 638 Nucleoside phosphorylase 3.2.2.16, 3.2.2.9 CAETHG_0741 CUU_c26600 CLRAG_08470 639 Predicted nuclease of the DUF1016 family of restriction endonuclease-like (RecB) protein superfamily CAETHG_0744 CUU_c26630 CLRAG_08500

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640 protein containing a domain with a 4Fe4S dicluster CAETHG_0749 CUU_c26680 CLRAG_08550 641 hypothetical protein CAETHG_0751 CUU_c26700 CLRAG_08570 642 uncharacterized protein CAETHG_0752 CUU_c26710 CLRAG_08580 643 insertase of membrane proteins of the YidC/Oxal family, protein containing a C-terminal domain CAETHG_0756 CUU_c26750 CLRAG_08620 644 hypothetical protein CAETHG_0757 CUU_c26760 CLRAG_08630 645 hypothetical protein CAETHG_0761 CUU_c26800 CLRAG_08670 646 Protein of the acetyltransferase family (GNAT) CAETHG_0768 CUU_c26840 CLRAG_08720 647 Non-characterized metal-binding agent protein CAETHG_0773 CUU_c37970, CUU_c26890 CLRAG_37360 648 Uncharacterized family protein (UPF0051) CAETHG_0774, CAETHG_1630 CLJU_c37930, CUU_c26900 CLRAG_37320 649 Predicted permease CAETHG_0776 CUU_c26920 CLRAG_08770 650 Predicted permease CAETHG_0777 CUU_c26930 CLRAG_08780 651 ABC-2 family transport protein CAETHG_0789 CUU_c27060 CLRAG_08820 652 Protoporphyrinogen IX oxidase, menaquinone dependent (flavodoxin domain) CAETHG_0795 CUU_c27100 CLRAG_08880 653 hypothetical protein CAETHG_0800 CUU_c27140 CLRAG_20090 654 ABC-2 family transport protein CAETHG_0801 CUU_c27150 CLRAG_20080 655 hypothetical protein CAETHG_0802, CAETHG_2198 CLJU_c00830, CUU_c27160 CLRAG_20070 656 hypothetical protein CAETHG_0811, CAETHG_3994 CLJU_c27250, CUU_cl8750 CLRAG_16540 657 SpoOE-like regulatory protein sporulation CAETHG_0824 CUU_c28270 CLRAG_34350 658 Serine phosphatase RsbU, sigma subunit regulator CAETHG_0827 CUU_c28300 CLRAG_34380 659 protein of unknown function (DUF1987) CAETHG_0828 CUU_c28310 CLRAG_34390 660 hypothetical protein CAETHG_0829 CUU_c28320 CLRAG_34400 661 protein of unknown function (DUF4317) CAETHG_0830 CUU_c28330 CLRAG_34410 662 HesB-like selenoprotein CAETHG_0831 CUU_c28340 CLRAG_34420 663 IDEAL domain-containing protein CAETHG_0835 CUU_c28380 CLRAG_34460 664 Protein of the PD-(D/E)XK nuclease superfamily CAETHG_0836 CUU_c28390 CLRAG_34470 665 hypothetical protein CAETHG_0839 CUU_c28410 CLRAG_34490 666 putative hemolysin CAETHG_0841 CUU_c28430 CLRAG_34510 667 SpoOE-like regulatory protein sporulation CAETHG_0842 CUU_c28470 CLRAG_34550 668 hypothetical protein CAETHG_0846 CUU_c28510 CLRAG_34590 669 Uncharacterized membrane protein CAETHG_0850, CAETHG_4038 CUU_c28560, CUU_cl9040 CLRAG_34630 670 hypothetical protein CAETHG_0852 CUU_c28570 CLRAG_34640 671 hypothetical protein CAETHG_0857 CUU_c28620 CLRAG_34700 672 hypothetical protein CAETHG_0873 CUU_c28780 CLRAG_34860 673 Putative TadE/G-like pili assembly protein FIP CAETHG_0880 CUU_c28840 CLRAG_34920 674 pili assembly protein Flp/PilA CAETHG_0882 CUU_c28860 CLRAG_34940 675 hypothetical protein CAETHG_0886 CUU_c28900 CLRAG_34980 676 Tryptophan transporter TgrR CAETHG_0892 CUU_c29000 CLRAG_35000 677 CBS domain-containing protein 1.1.1.205 CAETHG_0893 CUU_c29010 CLRAG_35010 678 hypothetical protein CAETHG_0894 CUU_c29020 CLRAG_35020 679 HNH endonuclease CAETHG_0895 CUU_c29030 CLRAG_35030 680 A 40-residue protein containing CAETHG_0900 CUU_c29080 CLRAG_35080

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repeat beta propeller of the YVTN family 681 L,D-transpeptidase, catalytic domain CAETHG_0901 CLJU_c29090 CLRAG_35090 682 Uncharacterized Yuke conserved protein CAETHG_0902 CUU_c29100 CLRAG_35100 683 hypothetical protein CAETHG_0911 CUU_c29190 CLRAG_35190 684 Uncharacterized conserved YgiM protein containing an N-terminal SH3 domain of the DUF1202 family 3.5.1.28 CAETHG_0912 CLJU_c29200 CLRAG_35200 685 hypothetical protein CAETHG_0918 CUU_c29250 CLRAG_35260 686 class II c-di-GMP phosphodiesterase (or its inactivated variant), HD-GYP domain CAETHG_0919 CUU_c29260 CLRAG_35270 687 2'-5'-RNA ligase CAETHG_0921 CUU_c29280 CLRAG_35290 688 hypothetical protein CAETHG_0922 CUU_c29290 CLRAG_35300 689 Protein of unknown function (DUF2000) CAETHG_0925 CUU_c29320 CLRAG_35330 690 protein of unknown function (DUF3787) CAETHG_0929 CUU_c29350 CLRAG_35370 691 SEC-C motif-containing protein CAETHG_0941 CUU_c29470 CLRAG_35460 692 hypothetical protein CAETHG_0942 CUU_c29480 CLRAG_35470 693 probable redox protein of the C_GCAxxG_C_C family CAETHG_0946 CUU_c29520 CLRAG_35510 694 hypothetical protein CAETHG_0965 CUU_c29670 CLRAG_35670 695 hypothetical protein CAETHG_0967 CUU_c29690 CLRAG_35690 696 hypothetical protein CAETHG_0973 CUU_c29740 CLRAG_35740 697 GDSL-like lipase/acyl hydrolase CAETHG_0975 CUU_c29760 CLRAG_35760 698 Protein of unknown function (DUF3189) CAETHG_0976 CUU_c29770 CLRAG_35770 699 hypothetical protein CAETHG_0979 CUU_c29800 CLRAG_35810 700 hypothetical protein CAETHG_0981 CUU_c29820 CLRAG_35830 701 C-terminal domain of PrcB CAETHG_0985 CUU_c29860 CLRAG_35870 702 protein of unknown function (DUF4367) CAETHG_0986 CUU_c29870 CLRAG_35880 703 Predicted transcriptional regulator YheO containing PAS and DNA-binding HTH domains CAETHG_1000 CUU_c30010 CLRAG_15650 704 probable DNA metabolism protein CAETHG_1035, CAETHG_1044 CLJU_c30390, CUU_c30280 CLRAG_15920 705 YoaP-like protein CAETHG_1063 CUU_c30590 CLRAG_16000 706 hypothetical protein CAETHG_1075 CUU_c30710 CLRAG_16150 707 hypothetical protein CAETHG_1076 CUU_c30720 CLRAG_16160 708 hypothetical protein CAETHG_1083 CUU_c30790 CLRAG_16230 709 hypothetical protein CAETHG_1084 CUU_c30800 CLRAG_16240 710 Putative protein containing amidase domain CAETHG_1091, CAETHG_1144 CLJU_c32160, CUU_c30880 CLRAG_16290 711 DNA-binding transcriptional regulator of the FrmR family CAETHG_1142 CUU_c32140 CLRAG_02770 712 hypothetical protein CAETHG_1145 CUU_c32170 CLRAG_02800 713 Protein of unknown function (DUF3892) CAETHG_1148 CLJU_c32200 CLRAG_02830 714 MA superfamily peptidase CAETHG_1149 CLJU_c32210 CLRAG_02840 715 Uncharacterized membrane protein CAETHG_1150 CUU_c32220 CLRAG_03040 716 YvrJ family protein CAETHG_1166, CAETHG_1657 CLJU_c32550, CUU_c32360 CLRAG_37650 717 Protein of unknown function (DUF1659) CAETHG_1167, CAETHG_1656 CLJU_c32560, CUU_c32370 CLRAG_29820 718 Protein of unknown function (DUF2922) CAETHG_1168, CAETHG_1655 CLJU_c32380, CUU_c32570 CLRAG_29830 719 protein of unknown function (DUF3786) CAETHG_1174, CAETHG_1517 CUU_c32760, CUU_c36080 CLRAG_06590

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720 Protein of unknown function (DUF2992) CAETHG_1180 CUU_c32820 CLRAG_15510 721 hypothetical protein CAETHG_1183 CUU_c32850 CLRAG_15480 722 hypothetical protein CAETHG_1184 CUU_c32860 CLRAG_15470 723 Phospholipid methyltransferase CAETHG_1188 CLJU_c32900 CLRAG_15430 724 LiaG protein of the lia operon CAETHG_1189 CUU_c32910 CLRAG_15420 725 hypothetical protein CAETHG_1190 CUU_c32920 CLRAG_15410 726 Dolichyl phosphate mannose protein mannosyltransferase CAETHG_1196, CAETHG_3415 CUU_c32980, CLJU_cl3320 CLRAG_15350 727 hypothetical protein CAETHG_1197 CUU_c32990 CLRAG_15340 728 ABC-2 transport system permease protein CAETHG_1198 CUU_c33000 CLRAG_15330 729 Dehalogenase superfamily protein halogen acid class (subfamily) HA/variant 1 of the halogen acid dehalogenase superfamily of subfamily IA, containing Dx(3-4)D or Dx(3-4)E in the third motif CAETHG_1205 CLJU_c33070 CLRAG_15260 730 TIGR00659 family protein CAETHG_1206 CUU_c33080 CLRAG_15250 731 choline-like protein CAETHG_1207 CLJU_c33090 CLRAG_15240 732 hypothetical protein CAETHG_1222 CLJU_c33230 CLRAG_15030 733 hypothetical protein CAETHG_1228 CLJU_c33290 CLRAG_14970 734 Uncharacterized membrane protein CAETHG_1231 CLJU_c33320 CLRAG_14940 735 Uncharacterized YtfJ spore protein CAETHG_1234 CLJU_c33340 CLRAG_14910 736 Protein of unknown function (DUF2953) CAETHG_1235 CLJU_c33350 CLRAG_14900 737 hypothetical protein CAETHG_1236 CUU_c33360 CLRAG_14890 738 Lecithin retinol acyltransferase CAETHG_1237 CLJU_c33370 CLRAG_14880 739 CotF spore coat protein CAETHG_1239 CLJU_c33390 CLRAG_14860 740 Spore coat-associated protein JA (CotJA) CAETHG_1240 CLJU_c33400 CLRAG_14850 741 hypothetical protein CAETHG_1244 CLJU_c33440 CLRAG_32320 742 Protein of unknown function (DUF3100) CAETHG_1245 CUU_c33450 CLRAG_32310 743 hypothetical protein CAETHG_1254 CUU_c33550 CLRAG_24730 744 hypothetical protein CAETHG_1260 CUU_c33620 CLRAG_24660 745 MEDS: methanogen/methylotroph, DcmR sensor domain CAETHG_1261 CUU_c33630 CLRAG_24650 746 hypothetical protein CAETHG_1263 CUU_c33650 CLRAG_24630 747 oxygen-independent coproporphyrinogen 3 oxidase CAETHG_1266 CUU_c33680 CLRAG_24600 748 SCIFF peptide containing six cysteine residues CAETHG_1275 CLJU_c33770 CLRAG_24510 749 putative membrane protein of the TIGR04086 family CAETHG_1276 CUU_c33780 CLRAG_24500 750 YajC translocase subunit preprotein CAETHG_1277 CUU_c33790 CLRAG_24490 751 hypothetical protein CAETHG_1282 CUU_c33840 CLRAG_24440 752 Protein UPF0755 CAETHG_1284 CUU_c33860 CLRAG_24420 753 DNA-binding regulatory protein of the YebC/PmpR family CAETHG_1285 CUU_c33870 CLRAG_14020 754 uncharacterized protein of the YigZ family CAETHG_1286 CUU_c33880 CLRAG_14030 755 hypothetical protein CAETHG_1288 CLJU_c33900 CLRAG_14050 756 YunB sporulation protein CAETHG_1291 CLJU_c33930 CLRAG_14080 757 O-antigen ligase CAETHG_1304 CLJU_c34060 CLRAG_14210 758 oligosaccharide repeat unit polymerase CAETHG_1312 CUU_c34140 CLRAG_14290 759 hypothetical protein CAETHG_1324, CAETHG_1332 CUU_c34320, CUU_c34250 CLRAG_14380

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760 Uncharacterized conserved YbbK protein of the DUF523 family CAETHG_1337 CUU_c34370 CLRAG_14450 761 cell division protein ZapA CAETHG_1340 CUU_c34400 CLRAG_14480 762 putative sporulation protein YtxC CAETHG_1348 CUU_c34480 CLRAG_14560 763 Putative protein containing peptidoglycan binding domain CAETHG_1349 CUU_c34530 CLRAG_14610 764 hypothetical protein CAETHG_1359 CLJU_c34630 CLRAG_14710 765 protein of unknown function (DUF4364) CAETHG_1361 CUU_c34650 CLRAG_14730 766 A 40-residue protein containing the YVTN family beta-propeller repeat CAETHG_1363 CUU_c34660 CLRAG_14740 767 uncharacterized protein TIGR03905 CAETHG_1364 CUU_c34670 CLRAG_14750 768 hypothetical protein CAETHG_1367 CLJU_c34700 CLRAG_14780 769 substrate-binding protein of the transport system of the NitT/TauT family CAETHG_1368 CUU_c34710 CLRAG_14790 770 Protein of unknown function (DUF2812) CAETHG_1381 CUU_c34830 CLRAG_26070 771 Csta protein of the bactofilin family CAETHG_1389 CUU_c34910 CLRAG_26150 772 Protein of unknown function (DUF4004) CAETHG_1390 CUU_c34920 CLRAG_26160 773 Polyketide cyclase/dehydrase CAETHG_1407 CLJU_c34980 CLRAG_26250 774 AAA domain-containing protein CAETHG_1408 CUU_c34990 CLRAG_26260 775 S factor transporter energy metabolism, ThiW component CAETHG_1414 CUU_c35050 CLRAG_26310 776 DNA-binding transcriptional regulator of the PadR family CAETHG_1421 CUU_c35120 CLRAG_26370 777 ABC-2 transport system permease protein CAETHG_1428 CUU_c35200 CLRAG_05710 778 ABC-2 transport system permease protein CAETHG_1429 CUU_c35210 CLRAG_05720 779 Uncharacterized conserved protein YurZ family alkylhydroperoxidase/carboxymuconolactone decarboxylase CAETHG_1430 CUU_c35220 CLRAG_05730 780 putative membrane protein CAETHG_1433 CUU_c35250 CLRAG_05760 781 substrate-binding protein of the transport system of the NitT/TauT family CAETHG_1441 CUU_c35320 CLRAG_05850 782 Tetratricopeptide repeat-containing protein CAETHG_1446 CUU_c35380 CLRAG_05920 783 Uncharacterized membrane-bound YitT protein containing DUF161 and DUF2179 domains CAETHG_1454 CUU_c35460 CLRAG_05990 784 protein containing a redox disulfide domain associated with hybrid cluster proteins CAETHG_1457, CAETHG_3809, CAETHG_1458 CLJU_c35500, CLJU_c35490, CUU_cl6990 CLRAG_06020 785 repeat domain-containing protein CAETHG_1465 CUU_c35570 CLRAG_06100 786 hypothetical protein CAETHG_1467 CUU_c35590 CLRAG_06120 787 CAAX protease of autoimmunity CAETHG_1468 CUU_c35600 CLRAG_06130 788 hypothetical protein CAETHG_1475 CUU_c35670 CLRAG_06200 789 Protein of unknown function (DUF3343) CAETHG_1483 CUU_c35750 CLRAG_06280 790 Uncharacterized membrane-bound YitT protein containing DUF161 and DUF2179 domains CAETHG_1487 CUU_c35790 CLRAG_06320 791 Probable zinc ribbon domain-containing protein CAETHG_1488, CAETHG_1680 CLJU_c38240, CUU_c35800 CLRAG_06330 792 Dihydropyrimidine dehydrogenase (NAD+), ProT subunit CAETHG_1495 CUU_c35880 CLRAG_06380 793 hypothetical protein CAETHG_1505 CUU_c35970 CLRAG_06470 794 hypothetical protein CAETHG_1515 CUU_c36060 CLRAG_06550 795 YvrJ family protein CAETHG_1516 CUU_c36070 CLRAG_06560

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796 hypothetical protein CAETHG_1522 CUU_c36120 CLRAG_06650 797 hypothetical protein CAETHG_1528 CUU_c36180 CLRAG_24000 798 hypothetical protein CAETHG_1529 CUU_c36190 CLRAG_23990 799 hypothetical protein CAETHG_1540 CUU_c36320 CLRAG_23840 800 hypothetical protein CAETHG_1549 CUU_c36880 CLRAG_36410 801 hypothetical protein CAETHG_1551 CUU_c36900 CLRAG_36430 802 hypothetical protein CAETHG_1557 CUU_c36960 CLRAG_36500 803 hypothetical protein CAETHG_1564 CUU_c37090 CLRAG_36570 804 hypothetical protein CAETHG_1565 CUU_c37100 CLRAG_36580 805 Uncharacterized membrane protein YdjX of the TVP38/TMEM64 family, SNARE-associated domain CAETHG_1574 CUU_c37210 CLRAG_36650 806 uncharacterized protein of the MTH1187 family CAETHG_1587 CUU_c37310 CLRAG_36750 807 protein of unknown function (DUF1836) CAETHG_1597 CUU_c37450 CLRAG_36860 808 Protein containing the CxxC motif CAETHG_1598 CUU_c37460 CLRAG_36870 809 protein of unknown function (DUF3786) CAETHG_1603 CUU_c37500 CLRAG_36910 810 hypothetical protein CAETHG_1604 CLJU_c22610, CUU_c37510 CLRAG_36920 811 Predicted RNA-binding protein CAETHG_1605 CUU_c37520 CLRAG_36930 812 methylenetetrahydrofolate reductase, C-terminal domain 1.5.1.20 CAETHG_1615 CUU_c37620 CLRAG_37030 813 hypothetical protein CAETHG_1626 CUU_c37790 CLRAG_37210 814 conserved hypothetical integral membrane protein CAETHG_1628 CUU_c37810 CLRAG_37230 815 MOSC domain-containing protein CAETHG_1632 CUU_c38010 CLRAG_37380 816 hypothetical protein CAETHG_1635 CUU_c38110 CLRAG_37480 817 hypothetical protein CAETHG_1639 CUU_c38130 CLRAG_37530 818 Protein of unknown function (DUF1653) CAETHG_1644, CAETHG_2926 CUU_c08310 CLRAG_08090 819 protein containing DnaD- and phage-associated domain CAETHG_1665 CUU_c32520 CLRAG_36090 820 hypothetical protein CAETHG_1678 CUU_c38220 CLRAG_20680 821 Predicted transcriptional regulator containing an HTH domain CAETHG_1679 CUU_c38230 CLRAG_20690 822 Uncharacterized membrane protein CAETHG_1681 CUU_c38250 CLRAG_20710 823 Protein containing the sequence motif GxGYxY CAETHG_1695 CUU_c38370 CLRAG_20840 824 hypothetical protein CAETHG_1699 CUU_c38440 CLRAG_20880 825 hypothetical protein CAETHG_1751 CUU_c31340 CLRAG_21210 826 translocase subunit preprotein SecG CAETHG_1755 CUU_c39100 CLRAG_21250 827 hypothetical protein CAETHG_1766 CUU_c39210 CLRAG_21360 828 Threonine/homoserine efflux transporter RhtA CAETHG_1767 CUU_c39220 CLRAG_21430 829 Protein containing an lg-like domain CAETHG_1778 CUU_c39330 CLRAG_21540 830 hypothetical protein CAETHG_1783 CUU_c39380 CLRAG_21590 831 hypothetical protein CAETHG_1792 CUU_c39470 CLRAG_21680 832 hypothetical protein CAETHG_1793 CUU_c39480 CLRAG_21690 833 hypothetical protein CAETHG_1794 CUU_c39490 CLRAG_21700 834 hypothetical protein CAETHG_1798 CUU_c39530 CLRAG_21730 835 homoserine kinase CAETHG_1811 CUU_c39650 CLRAG_21900 836 Protein of the PadR transcriptional regulator-like protein family CAETHG_1833, CAETHG_1835 CUU_c39890, CUU_c39870 CLRAG_22120

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837 Efflux transporter - protein multidrug resistance CAETHG_1834, CAETHG_1836 CLJU_c39900, CUU_c39880 CLRAG_22130 838 membrane protein DedA, SNARE-associated domain CAETHG_1842 CUU_c39960 CLRAG_22190 839 Putative protein containing amidase domain CAETHG_1849 CLJU_c40020 CLRAG_22250 840 Mog transcription activator family protein CAETHG_1856 CUU_c40070 CLRAG_22330 841 phosphopantothenoylcysteine decarboxylase/phosphopantothenate cysteine ligase 4.1.1.36, 6.3.2.5 CAETHG_1863 CLJU_c40140 CLRAG_22370 842 protein of unknown function (DUF4177) CAETHG_1886 CUU_c40430 CLRAG_22620 843 YbbR domain-containing protein CAETHG_1889 CLJU_c40460 CLRAG_22650 844 diadenylate cyclase CAETHG_1890 CLJU_c40470 CLRAG_22660 845 protein of unknown function (DUF4652) CAETHG_1895 CUU_c40520 CLRAG_22710 846 ribonuclease-3 family protein CAETHG_1967 CUU_c41260 CLRAG_23450 847 Uncharacterized conserved YacL protein containing PIN and TRAM domains CAETHG_1970 CUU_c41290 CLRAG_23480 848 hypothetical protein CAETHG_1971 CLJU_c41300 CLRAG_23490 849 hypothetical protein CAETHG_1978 CUU_c41370 CLRAG_23560 850 hypothetical protein 2.6.1.11 CAETHG_1984 CUU_c41500 CLRAG_04630 851 cell division protein FtsL CAETHG_1992 CUU_c41630 CLRAG_04760 852 spore cortex biosynthesis protein YabQ CAETHG_1993 CUU_c41640 CLRAG_04770 853 YabP sporulation protein CAETHG_1994 CUU_c41650 CLRAG_04780 854 Tetrapyrrole methylase family protein / MazG family protein CAETHG_1997 CUU_c41680 CLRAG_04810 855 hypothetical protein CAETHG_2011 CUU_c41820 CLRAG_04950 856 hypothetical protein CAETHG_2016 CUU_c41870 CLRAG_04980 857 hypothetical protein CAETHG_2019 CLJU_c41900 CLRAG_05010 858 Uncharacterized membrane protein Ykvl CAETHG_2020 CUU_c41910 CLRAG_05020 859 protein of the 2'-5'-RNA ligase superfamily CAETHG_2025 CUU_c41960 CLRAG_05070 860 protein of unknown function (DUF1540) CAETHG_2026 CUU_c41970 CLRAG_05080 861 Protein CxxH/CxxC family BA_5709 CAETHG_2029 CLJU_c42000 CLRAG_05110 862 SEC-C motif-containing protein CAETHG_2031 CLJU_c42010 CLRAG_05120 863 F5/8 C-domain-containing protein CAETHG_2032 CLJU_c42020 CLRAG_05130 864 putative regulator of the iron-only hydrogenase system CAETHG_2034 CLJU_c42040 CLRAG_05150 865 Dimeric dUTPase of the all-alpha NTP-PPase superfamily (MazG) CAETHG_2035 CUU_c42050 CLRAG_05160 866 transporter family protein-2 CAETHG_2036 CUU_c42060 CLRAG_05170 867 NAD(P)H-dependent flavin oxidoreductase YrpB family nitropropane dioxygenase CAETHG_2052 CUU_c42210 CLRAG_05320 868 Predicted CoA-binding protein CAETHG_2056 CUU_c42320 CLRAG_05430 869 Cupin domain-containing protein CAETHG_2068 CUU_c42430 CLRAG_05570 870 Putative ABC transporter type IV CAETHG_2072 CUU_c42470 CLRAG_05580 871 MazG-like protein family protein CAETHG_2102 CUU_c42760 CLRAG_25570 872 hypothetical protein CAETHG_2106 CUU_c42800 CLRAG_25610 873 Protein of unknown function (DUF3343) CAETHG_2108 CUU_c42820 CLRAG_25630 874 integral membrane protein of sporulation Ytvl CAETHG_2109 CUU_c42830 CLRAG_25640 875 putative sporulation protein YyaC CAETHG_2110 CUU_c42840 CLRAG_25650 876 Uncharacterized family protein (UPF0180) CAETHG_2111 CUU_c42850 CLRAG_25660 877 Protein of unknown function (DUF4446) CAETHG_2112 CUU_c42860 CLRAG_25670

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878 hypothetical protein CAETHG_2121 CUU_c42950 CLRAG_25760 879 ribosome associated protein CAETHG_2126 CUU_c00030 CLRAG_25810 880 protein of unknown function (DUF370) CAETHG_2128 CLJU_cOOO5O CLRAG_25830 881 HDIG domain-containing protein CAETHG_2131 CLJU_cOO12O CLRAG_20200 882 hypothetical protein CAETHG_2133 CLJU_c00140 CLRAG_20180 883 Protein of unknown function (DUF1667) CAETHG_2136 CUU_c00160 CLRAG_20160 884 hypothetical protein CAETHG_2173 CUU_c00550 CLRAG_20020 885 Mannose-6-phosphate isomerase of the cupin superfamily CAETHG_2181 CUU_c00630 CLRAG_19950 886 Phasin polyhydroxyalkanoate synthesis regulator CAETHG_2191 CLJU_c00740 CLRAG_19840 887 hypothetical protein CAETHG_2200 CUU_c00860 CLRAG_19720 888 Protein of unknown function (DUF2508) CAETHG_2202 CUU_c00880 CLRAG_19700 889 pro-sigma K processing inhibitor CAETHG_2203 CUU_c00890 CLRAG_19690 890 hypothetical protein CAETHG_2206, CAETHG_2756 CUU_c06660, CLJU_cOO92O CLRAG_19660 891 protein containing a domain with a 4Fe4S dicluster CAETHG_2207 CLJU_cOO93O CLRAG_19650 892 hypothetical protein CAETHG_2208 CLJU_c00940 CLRAG_19640 893 hypothetical protein CAETHG_2209 CUU_c00950 CLRAG_19630 894 hypothetical protein CAETHG_2240 CUU_c01340 CLRAG_27000 895 Sigma-G Inhibitor Gin CAETHG_2243 CUU_cO137O CLRAG_27030 896 Uncharacterized YaaQ protein CAETHG_2246 CLJU_c01400 CLRAG_27060 897 Copper chaperone CopZ CAETHG_2249 CUU_c01430 CLRAG_27090 898 NIpC family hydrolase associated with cell wall CAETHG_2255, CAETHG_2256 CUU_c01500, CUU_c01490 CLRAG_27150 899 hypothetical protein CAETHG_2259 CUU_c01530 CLRAG_27190 900 protein of unknown function (DUF1836) CAETHG_2262 CUU_c01560 CLRAG_27220 901 hypothetical protein CAETHG_2264 CUU_c01580 CLRAG_27240 902 hypothetical protein CAETHG_2270 CUU_c01680 CLRAG_27280 903 hypothetical protein CAETHG_2271 CUU_c01690 CLRAG_27290 904 protein of unknown function (DUF348) CAETHG_2277 CUU_c01750 CLRAG_27350 905 ribonuclease M5 CAETHG_2278 CUU_c01760 CLRAG_27360 906 hypothetical protein CAETHG_2281 CUU_c01780 CLRAG_27380 907 hypothetical protein CAETHG_2282 CUU_c01790 CLRAG_27390 908 hypothetical protein CAETHG_2283 CUU_c01800 CLRAG_27400 909 hypothetical protein CAETHG_2286 CUU_c01830 CLRAG_27430 910 membrane protein DedA, SNARE-associated domain CAETHG_2294 CUU_c01910 CLRAG_27510 911 Protein containing a fragment of the AAA domain CAETHG_2295 CUU_c01920 CLRAG_27520 912 putative endonuclease CAETHG_2297 CUU_c01940 CLRAG_27540 913 hypothetical protein CAETHG_2299 CUU_c01960 CLRAG_27560 914 Uncharacterized Veg protein CAETHG_2312 CUU_c02070 CLRAG_27670 915 protein of unknown function (DUF3794) CAETHG_2313 CUU_c02080 CLRAG_27680 916 hypothetical protein CAETHG_2317 CUU_c02120 CLRAG_27720 917 Uncharacterized YwiB protein of the DUF1934 family containing a beta-barrel motif CAETHG_2323 CUU_c02180 CLRAG_27780 918 hypothetical protein CAETHG_2326 CUU_c02210 CLRAG_27810 919 Uncharacterized conserved protein YqhQ CAETHG_2329 CLJU_c02240 CLRAG_27840 920 hypothetical protein CAETHG_2332 CLJU_cO227O CLRAG_27870

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921 TATA box binding protein CAETHG_2351 CUU_cO245O CLRAG_28060 922 putative sporulation protein YyaC CAETHG_2357 CUU_cO252O CLRAG_28120 923 hypothetical protein CAETHG_2360 CUU_cO26OO CLRAG_28200 924 Riboflavin transporter FmnP CAETHG_2370 CUU_cO269O CLRAG_28290 925 hypothetical protein CAETHG_2372 CUU_cO27OO CLRAG_28300 926 flagellar biosynthesis protein CAETHG_2373 CUU_cO271O CLRAG_28310 927 hypothetical protein CAETHG_2378 CUU_c02770 CLRAG_28370 928 DnaJ domain-containing protein CAETHG_2379 CLJU_cO278O CLRAG_28380 929 hypothetical protein CAETHG_2380 CUU_cO279O CLRAG_28390 930 protein of unknown function (DUF4363) CAETHG_2383 CUU_cO282O CLRAG_28420 931 Uncharacterized membrane protein YcaP family DUF421 CAETHG_2384 CUU_cO283O CLRAG_28430 932 uridine kinase 2.7.1.48 CAETHG_2385 CUU_cO284O CLRAG_28440 933 serine/threonine protein kinase RsbW CAETHG_2403 CUU_cO288O CLRAG_28480 934 hypothetical protein CAETHG_2405 CUU_c02900 CLRAG_28500 935 Uncharacterized membrane protein YdjX of the TVP38/TMEM64 family, SNARE-associated domain CAETHG_2407 CUU_c02920 CLRAG_28520 936 CBS domain-containing protein 1.1.1.205 CAETHG_2408 CUU_cO293O CLRAG_28530 937 hypothetical protein CAETHG_2410 CUU_cO295O CLRAG_28560 938 hypothetical protein CAETHG_2414 CUU_c02990 CLRAG_28600 939 Lipoprotein-sorting outer membrane protein CAETHG_2417 CUU_c03020 CLRAG_28630 940 PDZ domain-containing protein CAETHG_2425 CUU_c03100 CLRAG_28710 941 Protein containing a Forkhead-associated (EHA) domain that binds pSer, pThr, pTyr CAETHG_2428 CUU_c03130 CLRAG_28740 942 inner membrane protein CAETHG_2431 CUU_c03160 CLRAG_28770 943 nucleotide binding protein UPF0042 CAETHG_2434 CUU_cO319O CLRAG_28800 944 conserved hypothetical protein, related to cofD CAETHG_2435 CUU_c03200 CLRAG_28810 945 hypothetical protein CAETHG_2436 CUU_c03210 CLRAG_28820 946 Uncharacterized conserved YgbK protein of the DUF1537 family CAETHG_2444 CUU_cO382O CLRAG_28890 947 Uncharacterized family protein (UPF0180) CAETHG_2451 CUU_cO389O CLRAG_29000 948 protein of unknown function (DUF3870) CAETHG_2455 CUU_c03930 CLRAG_29040 949 membrane protein RarD containing EatAdomain CAETHG_2456 CUU_cO394O CLRAG_29050 950 Protein containing a methyltransferase domain CAETHG_2473 CUU_cO41OO CLRAG_26950 951 hypothetical protein CAETHG_2489 CUU_cO421O CLRAG_26850 952 hypothetical protein CAETHG_2490 CUU_cO422O CLRAG_26840 953 hypothetical protein CAETHG_2491 CUU_cO423O CLRAG_26830 954 An uncharacterized protein containing an NRPS condensation (elongation) domain CAETHG_2492 CUU_c04240 CLRAG_26790 955 hypothetical protein CAETHG_2500 CUU_cO432O CLRAG_26730 956 Putative flipase GtrA (bactoprenol-linked glucose transmembrane translocase) CAETHG_2518 CUU_cO446O CLRAG_37820 957 Protein of unknown function (DUF2837) CAETHG_2522 CUU_cO45OO CLRAG_37860 958 GPI transamidase subunit PIG-U CAETHG_2524 CUU_cO452O CLRAG_37880 959 TGF-beta propeptide CAETHG_2525 CUU_cO453O CLRAG_37890 960 ABC-2 transport system permease protein CAETHG_2529 CUU_cO457O CLRAG_37930

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961 Uncharacterized membrane protein CAETHG_2536 CUU_c04640 CLRAG_38000 962 Protein of unknown function (DUF116) CAETHG_2539 CUU_c04670 CLRAG_38050 963 hypothetical protein CAETHG_2542 CLJU_c04700 CLRAG_38080 964 hypothetical protein CAETHG_2543 CUU_c04710 CLRAG_38090 965 hypothetical protein CAETHG_2544 CUU_c04720 CLRAG_38100 966 hypothetical protein CAETHG_2552 CUU_c04800 CLRAG_38180 967 hypothetical protein CAETHG_2553 CUU_c04810 CLRAG_38190 968 Putative cell wall binding protein containing repeat 2 CAETHG_2555 CUU_c04830 CLRAG_38210 969 Spore coat assembly protein SafA/uncharacterized YkwD family protein CAETHG_2563 CUU_c04860 CLRAG_38250 970 Outer membrane protein TolC CAETHG_2583 CUU_c05060 CLRAG_38450 971 Outer membrane efflux protein CAETHG_2584 CUU_c05070 CLRAG_38460 972 ResB family protein CAETHG_2585 CUU_c05080 CLRAG_38470 973 WG-containing repeat protein CAETHG_2586 CUU_c05090 CLRAG_38480 974 SLAP domain-containing protein CAETHG_2587 CUU_c05100 CLRAG_38490 975 hypothetical protein (DUF2140) CAETHG_2590 CUU_c05130 CLRAG_38520 976 Protein of unknown function (DUF1659) CAETHG_2594 CUU_c05170 CLRAG_38560 977 Protein of unknown function (DUF2922) CAETHG_2595 CUU_c05180 CLRAG_38570 978 sigma factor specific for sporulation RNA polymerase CAETHG_2596 CUU_c05190 CLRAG_38580 979 O-antigen polymerase CAETHG_2626 CUU_c05440 CLRAG_38900 980 Acetyltransferase (superfamily of proteins containing the isoleucine flap motif) CAETHG_2627 CUU_c05450 CLRAG_38910 981 asparagine synthase (glutamine-hydrolyzing) 6.3.5.4 CAETHG_2628 CUU_c05460 CLRAG_38920 982 Protein biosynthesis of polysaccharide capsule CAETHG_2629 CUU_c05470 CLRAG_38930 983 putative Mg2+ transporter-C (MgtC) family protein CAETHG_2654 CUU_c05620 CLRAG_06840 984 hypothetical protein CAETHG_2659 CUU_c05670 CLRAG_06900 985 hypothetical protein CAETHG_2660 CUU_c05680 CLRAG_06910 986 hypothetical protein CAETHG_2661 CUU_c05690 CLRAG_06920 987 von Willebrand factor type A domain-containing protein CAETHG_2662 CLJU_cO57OO CLRAG_06930 988 Tubulin-like protein CAETHG_2663 CUU_c05710 CLRAG_06940 989 hypothetical protein CAETHG_2664 CUU_c05720 CLRAG_06950 990 protein of the Ca-activated chloride channel family CAETHG_2666 CUU_c05730 CLRAG_06960 991 hypothetical protein CAETHG_2667 CUU_c05740 CLRAG_06970 992 GTP1/OBG protein CAETHG_2673 CUU_c05780 CLRAG_07030 993 hypothetical protein CAETHG_2674 CUU_c05790 CLRAG_07040 994 zinc ribbon domain-containing protein CAETHG_2675 CUU_c05800 CLRAG_07050 995 Protein of unknown function (DUF1861) CAETHG_2682 CUU_c05870 CLRAG_07110 996 VanZ-like protein family protein CAETHG_2690 CUU_c05930 CLRAG_07160 997 hypothetical protein CAETHG_2699 CUU_c06010 CLRAG_07240 998 Putative efflux pump Mn2+ MntP CAETHG_2705 CUU_c06060 CLRAG_07330 999 hypothetical protein CAETHG_2707 CUU_c06080 CLRAG_07350 1000 Uncharacterized membrane protein YkvA family DUF1232 CAETHG_2711 CUU_c06120 CLRAG_07400 1001 hypothetical protein CAETHG_2713 CUU_c06140 CLRAG_07420 1002 S41 family peptidase CAETHG_2742 CUU_c06460 CLRAG_30440 1003 hypothetical protein CAETHG_2763 CUU_c06720 CLRAG_18520

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1004 hypothetical protein CAETHG_2766 CUU_c06750 CLRAG_18550 1005 hypothetical protein CAETHG_2771 CUU_c06800 CLRAG_18600 1006 Carbonic anhydrase or acetyltransferase superfamily of proteins containing the isoleucine flap motif CAETHG_2776 CUU_cO685O CLRAG_18690 1007 hypothetical protein CAETHG_2778 CUU_c06870 CLRAG_18710 1008 Peptidoglycan/1_P5-O-acetylase OafA/YrhL, containing acyltransferase and SGNH hydrolase domains CAETHG_2781 CUU_c06910 CLRAG_18750 1009 Membrane protein involved in the regulation of membrane protease activity CAETHG_2783 CUU_c06930 CLRAG_18770 1010 hypothetical protein CAETHG_2787 CUU_c06970 CLRAG_18810 1011 Acetyltransferase domain-containing protein (GNAT) CAETHG_2809 CLJU_cO717O CLRAG_26670 1012 protein of unknown function (DUF4321) CAETHG_2811 CUU_c07190 CLRAG_26650 1013 protein associated with SAM radical CAETHG_2826 CUU_c07340 CLRAG_26500 1014 hypothetical protein CAETHG_2829 CUU_cO737O CLRAG_26470 1015 2-iminobutanoate/2-iminopropanoate deaminase CAETHG_2834 CUU_c07420 CLRAG_26420 1016 putative oxidative recovery protein CAETHG_2854 CUU_c07610 CLRAG_25180 1017 Protein containing the C-terminal domain of ribosomal protein L7/L12 CAETHG_2876 CUU_c07830 CLRAG_25300 1018 protein of unknown function (DUF4412) CAETHG_2878 CUU_c07850 CLRAG_25330 1019 hypothetical protein CAETHG_2879 CUU_c07860 CLRAG_25340 1020 CotEC competence protein CAETHG_2881 CUU_c07880 CLRAG_25360 1021 hypothetical protein CAETHG_2886 CUU_cO793O CLRAG_25410 1022 16S rRNA(uracil1498-N3)-methyltransferase CAETHG_2894 CUU_c08010 CLRAG_08350 1023 hypothetical protein CAETHG_2899 CUU_c08050 CLRAG_08310 1024 sporulation protein YqfC CAETHG_2900 CUU_c08060 CLRAG_08300 1025 probable rRNA maturation factor CAETHG_2903 CUU_c08080 CLRAG_08270 1026 protein of unknown function (DUF4342) CAETHG_2907 CUU_cO812O CLRAG_08230 1027 hypothetical protein CAETHG_2914 CUU_cO819O CLRAG_18740 1028 PH domain-containing protein CAETHG_2918 CUU_cO823O CLRAG_08160 1029 tRNA(adenine-22-N1)-methyltransferase CAETHG_2919 CUU_c08240 CLRAG_08150 1030 hypothetical protein CAETHG_2921 CUU_c08260 CLRAG_08130 1031 hypothetical protein CAETHG_2923 CUU_c08280 CLRAG_08100 1032 hypothetical protein CAETHG_2940 CUU_c08470 CLRAG_07990 1033 hypothetical protein CAETHG_2956 CUU_cO862O CLRAG_07870 1034 hypothetical protein CAETHG_2958 CUU_c08640 CLRAG_07850 1035 NADH quinone oxidoreductase, subunit F CAETHG_2962 CUU_c08680 CLRAG_07810 1036 hypothetical protein CAETHG_2970 CUU_c08760 CLRAG_07730 1037 hypothetical protein CAETHG_2977 CUU_c08820 CLRAG_07670 1038 hypothetical protein CAETHG_2982 CUU_c08870 CLRAG_07610 1039 Protein containing an lg-like domain CAETHG_2993 CUU_c08990 CLRAG_07520 1040 Uncharacterized YpuA protein of the DUF1002 family CAETHG_2995 CLJU_c09010 CLRAG_14010 1041 hypothetical protein CAETHG_2996 CLJU_cO9O2O CLRAG_14000 1042 Protein of unknown function (DUF1292) CAETHG_3030 CUU_c09350 CLRAG_13750 1043 hypothetical protein CAETHG_3033 CUU_cO938O CLRAG_13720 1044 FlgN protein CAETHG_3045 CUU_c09500 CLRAG_13600 1045 flagellum assembly factor FliW CAETHG_3048 CLJU_cO953O CLRAG_13570

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1046 hypothetical protein CAETHG_3051 CUU_c09560 CLRAG_13550 1047 hypothetical protein CAETHG_3057 CUU_c09620 CLRAG_13520 1048 IS66 C-terminal element CAETHG_3069 CLJU_cO976O, CUU_cO538O CLRAG_16790 1049 hypothetical protein CAETHG_3077 CUU_cO984O, CLJU_c05400 CLRAG_16740 1050 hypothetical protein CAETHG_3095 CLJU_cl0040 CLRAG_13320 1051 Bacterial IgG-like domain CAETHG_3098 CUU_cl0080 CLRAG_13290 1052 Uncharacterized membrane protein of the DUF441 family CAETHG_3100 CUU_cl0100 CLRAG_13270 1053 Protein of unknown function (DUF3867) CAETHG_3101 CUU_cl0110 CLRAG_13260 1054 phage uncharacterized protein TIGR01671 CAETHG_3102 CUU_cl0120 CLRAG_13250 1055 hypothetical protein CAETHG_3103 CUU_cl0130 CLRAG_13240 1056 hypothetical protein CAETHG_3107 CLJU_clO17O CLRAG_13200 1057 hypothetical protein CAETHG_3132 CUU_cl0420 CLRAG_12950 1058 hypothetical protein CAETHG_3133 CUU_cl0430 CLRAG_12940 1059 hypothetical protein CAETHG_3136 CUU_cl0460 CLRAG_12910 1060 hypothetical protein CAETHG_3139 CUU_cl0490 CLRAG_12880 1061 Protein MraZ CAETHG_3143 CUU_cl0530 CLRAG_12810 1062 cell division protein FtsL CAETHG_3145 CUU_cl0550 CLRAG_12790 1063 hypothetical protein CAETHG_3155 CUU_cl0650 CLRAG_12690 1064 cell division inhibitor SepF CAETHG_3156 CUU_cl0660 CLRAG_12680 1065 YggT family protein CAETHG_3157 CUU_cl0670 CLRAG_12670 1066 hypothetical protein CAETHG_3167 CLJU_clO77O CLRAG_12570 1067 Protein 5-isoprenylcysteine-Omethyltransferase Stel4 CAETHG_3171 CUU_clO82O CLRAG_22440 1068 autoinducible cyclic lactone peptide CAETHG_3176 CLJU_c28500, CUU_c25570 CLRAG_03770 1069 hypothetical protein CAETHG_3178 CUU_cl0880 CLRAG_02280 1070 RIA type IV pili assembly protein CAETHG_3181 CUU_cl0920 CLRAG_12540 1071 protein containing a prepilin-type N-terminal hydrolysis/methylation domain CAETHG_3182 CUU_cl0930 CLRAG_12530 1072 protein containing a prepilin-type N-terminal hydrolysis/methylation domain CAETHG_3184 CUU_cl0950 CLRAG_12510 1073 hypothetical protein CAETHG_3185 CUU_cl0960 CLRAG_12500 1074 hypothetical protein CAETHG_3186 CUU_cl0970 CLRAG_12490 1075 hypothetical protein CAETHG_3187 CUU_clO98O CLRAG_12480 1076 hypothetical protein CAETHG_3188 CUU_cl0990 CLRAG_12470 1077 hypothetical protein CAETHG_3191 CUU_cll020 CLRAG_12440 1078 hypothetical protein CAETHG_3213 CUU_cll230 CLRAG_12230 1079 sporulation protein YtfJ CAETHG_3222 CUU_cll310 CLRAG_12140 1080 Protein of unknown function (DUF2953) CAETHG_3223 CUU_cll320 CLRAG_12130 1081 hypothetical protein CAETHG_3225 CUU_cll340 CLRAG_12110 1082 hypothetical protein CAETHG_3234 CUU_cll430 CLRAG_12020 1083 protein of unknown function (DUF4397) CAETHG_3235 CUU_cll440 CLRAG_12010 1084 Domain with unknown function (DUF4883) CAETHG_3236 CUU_cll450 CLRAG_12000 1085 DNA-binding transcriptional regulator of the FrmR family CAETHG_3238 CUU_cll470 CLRAG_11980 1086 Uncharacterized membrane protein YjjB of the DUF3815 family CAETHG_3239 CUU_cll480 CLRAG_11970 1087 Uncharacterized membrane protein YjjP of the DUF1212 family CAETHG_3240 CUU_cll490 CLRAG_11960

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1088 hypothetical protein CAETHG_3244 CUU_cll530 CLRAG_11920 1089 PAP2 superfamily protein CAETHG_3267 CUU_cll760 CLRAG_11780 1090 hypothetical protein CAETHG_3270 CUU_cll790 CLRAG_11750 1091 Protein containing flavin reductase- similar domain CAETHG_3273 CUU_cll820 CLRAG_11720 1092 Uncharacterized YrrD protein containing a PRC-barrel domain CAETHG_3295 CLJU_cl2130 CLRAG_11670 1093 Uncharacterized family protein UPF0297 CAETHG_3298 CUU_cl2160 CLRAG_11640 1094 Protein of unknown function (DUF1292) CAETHG_3300 CUU_cl2180 CLRAG_11620 1095 Cell fate regulator YlbF of the YheA/YmcA/DUF963 family (controls sporulation, competence, biofilm development) CAETHG_3303 CUU_cl2210 CLRAG_11590 1096 conserved hypothetical protein CAETHG_3318 CUU_cl2360 CLRAG_11440 1097 hypothetical protein CAETHG_3326 CUU_cl2440 CLRAG_11360 1098 putative SAM radical enzyme family TIGR03279 CAETHG_3328 CUU_cl2460 CLRAG_11340 1099 TIGR00255 family protein CAETHG_3332 CUU_cl2500 CLRAG_11300 1100 hypothetical protein CAETHG_3333 CUU_cl2510 CLRAG_11290 1101 16S rRNA(guanine966-Н2)-methyltransferase CAETHG_3352 CUU_cl2710 CLRAG_11100 1102 hypothetical protein CAETHG_3354 CUU_cl2730 CLRAG_11080 1103 Predicted nucleotidyl transferase CAETHG_3357 CUU_cl2750 CLRAG_11050 1104 uncharacterized protein CAETHG_3360 CUU_cl2790 CLRAG_11020 1105 G istone acetyltransferase, component RNA polymerase-elongator complex CAETHG_3365 CUU_cl2840 CLRAG_10970 1106 hypothetical protein CAETHG_3369 CUU_cl2870 CLRAG_10930 1107 hypothetical protein CAETHG_3372 CUU_cl2900 CLRAG_10900 1108 putative endonuclease CAETHG_3379 CUU_cl2970 CLRAG_10830 1109 ribosome maturation factor RimP CAETHG_3394 CUU_cl3110 CLRAG_10680 1110 hypothetical protein CAETHG_3396 CUU_cl3130 CLRAG_10660 1111 sporulation protein of the YlmC/YmxH family CAETHG_3406 CLJU_cl3230 CLRAG_10560 1112 ribonuclease Y CAETHG_3412 CUU_cl3290 CLRAG_10500 1113 EamA-like transporter family protein CAETHG_3416 CUU_cl3330 CLRAG_10460 1114 hypothetical protein CAETHG_3419 CUU_cl3360 CLRAG_10430 1115 hypothetical protein CAETHG_3422 CUU_cl3380 CLRAG_10410 1116 Blal family transcription regulator, penicillinase repressor CAETHG_3431 CLJU_cl3550, CUU_cl3470 CLRAG_10320 1117 protein of unknown function (DUF4179) CAETHG_3441 CUU_cl3580 CLRAG_10280 1118 hypothetical protein CAETHG_3447 CUU_cl3650 CLRAG_10220 1119 uncharacterized protein of the PHOOYU family/protein A system AmmeMemoRadiSam/protein B system AmmeMemoRadiSam CAETHG_3448 CUU_cl3660 CLRAG_10210 1120 branched chain amino acid transport protein CAETHG_3452 CUU_cl3700 CLRAG_10170 1121 Phenylpyruvate tautomerase PptA, 4oxalocroton tautomerase family CAETHG_3455 CUU_cl3730 CLRAG_10120 1122 Predicted PurR-regulated permease RegM CAETHG_3457 CUU_cl3750 CLRAG_10100 1123 hypothetical protein CAETHG_3467 CUU_cl3840 CLRAG_10000 1124 An uncharacterized protein of the pyridoxamine 5'-phosphate oxidase (PNPOx-) family like) CAETHG_3468 CUU_cl3850 CLRAG_09990 1125 hypothetical protein CAETHG_3475, CAETHG_3476 CUU_cl3930, CUU_cl3920 CLRAG_09230

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1126 Protein D of coenzyme synthesis PQQ(PqqD) CAETHG_3478 CUU_cl3950 CLRAG_09260 1127 Protein with a winged helix-loop-helix DNA-binding motif CAETHG_3482 CUU_cl3990 CLRAG_09320 1128 Protein of unknown function (DUF3793) CAETHG_3485 CUU_cl4010 CLRAG_09340 1129 Cupin domain-containing protein CAETHG_3502 CUU_cl4200 CLRAG_09530 ISO hypothetical protein CAETHG_3548 CUU_c34970 CLRAG_16880 1131 L-cysteine desulfidase CAETHG_3563 CUU_cl4640 CLRAG_09920 1132 diguanylate cyclase domain-containing protein (GGDEF) CAETHG_3564 CUU_cl4650 CLRAG_20550 1133 diguanylate cyclase domain-containing protein (GGDEF) CAETHG_3580 CUU_cl4800 CLRAG_20310 1134 protein containing a conserved domain CAETHG_3591 CUU_cl4850 CLRAG_20270 1135 protein containing a conserved domain CAETHG_3592 CUU_cl4860 CLRAG_20260 1136 Uncharacterized membrane protein YczE CAETHG_3593 CUU_cl4870 CLRAG_20250 1137 hypothetical protein CAETHG_3612 CUU_cl5100 CLRAG_24270 1138 hypothetical protein CAETHG_3613 CUU_cl5110 CLRAG_24230 1139 5-methylcytosine-specific restriction enzyme B CAETHG_3617 CUU_cl5150 CLRAG_24200 1140 hypothetical protein CAETHG_3621 CUU_cl5190 CLRAG_24160 1141 hypothetical protein CAETHG_3622 CUU_cl5200 CLRAG_24150 1142 ABC-2 transport system permease protein CAETHG_3640 CUU_cl5380 CLRAG_24080 1143 ABC-2 transport system permease protein CAETHG_3641 CUU_cl5400 CLRAG_24070 1144 secretion protein of the HlyD family CAETHG_3642 CUU_cl5410 CLRAG_24060 1145 hypothetical protein CAETHG_3644 CUU_cl5430 CLRAG_24040 1146 Protein containing a pentapeptide repeat CAETHG_3657 CUU_cl5620 CLRAG_32630 1147 probable redox protein of the C_GCAxxG_C_C family CAETHG_3662 CUU_cl5630 CLRAG_32680 1148 Glycopeptide antibiotic resistance protein CAETHG_3675 CUU_cl5680 CLRAG_32830 1149 protein of unknown function (DUF4367) CAETHG_3679 CUU_cl5710 CLRAG_32870 1150 O-methyltransferase CAETHG_3683 CUU_cl5750 CLRAG_32910 1151 putative sporulation protein YtaF CAETHG_3694 CUU_cl5940 CLRAG_32970 1152 putative conserved protein UCP010219 CAETHG_3700 CUU_cl6060 CLRAG_33030 1153 protein of unknown function (DUF4363) CAETHG_3732 CUU_cl6380 CLRAG_33180 1154 Uncharacterized membrane protein YcaP family DUF421 CAETHG_3733 CUU_cl6390 CLRAG_33190 1155 protein of unknown function (DUF3870) CAETHG_3734 CUU_cl6400 CLRAG_33200 1156 hypothetical protein CAETHG_3818 CUU_cl7060 CLRAG_33930 1157 Peptidase A4 family protein CAETHG_3820 CUU_cl7080 CLRAG_33950 1158 hypothetical protein CAETHG_3821 CUU_cl7090 CLRAG_33960 1159 hypothetical protein CAETHG_3836, CAETHG_3837 CUU_cl7240, CUU_cl7230 CLRAG_34210 1160 DNA-binding transcriptional regulator of the MerR family CAETHG_3839 CUU_cl7260 CLRAG_34230 1161 protein of unknown function (DUF4342) CAETHG_3843 CUU_cl7300 CLRAG_29280 1162 23S rRNA-(pseudouridine1915-ыЗ)- methyltransferase CAETHG_3853 CUU_cl7400 CLRAG_01290 1163 hypothetical protein CAETHG_3858 CUU_cl7450 CLRAG_01260 1164 hypothetical protein CAETHG_3869 CUU_cl7610 CLRAG_01130 1165 Protein of unknown function (DUF3795) CAETHG_3873 CUU_cl7650 CLRAG_01090 1166 response regulator YcbB two-component CAETHG_3881 CUU_cl7730 CLRAG_00990

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systems 1167 hypothetical protein CAETHG_3883 CUU_cl7750 CLRAG_00970 1168 hypothetical protein CAETHG_3887 CUU_cl7790 CLRAG_00920 1169 hypothetical protein CAETHG_3888 CUU_cl7800 CLRAG_00910 1170 M28 family peptidase CAETHG_3891 CUU_cl7830 CLRAG_00880 1171 CheY chemotaxis protein or CheY-like REC (receiver) domain CAETHG_3894 CUU_cl7860 CLRAG_00800 1172 3-methyladenine DNA glycosylase AlkD CAETHG_3896 CUU_cl7880 CLRAG_00780 1173 membrane protein RarD containing EatAdomain CAETHG_3897 CUU_cl7890 CLRAG_00760 1174 auxiliary factor xanthine hydrogenase CAETHG_3903 CUU_cl7940 CLRAG_00690 1175 diguanylate cyclase domain-containing protein (GGDEF) CAETHG_3905 CUU_cl7960 CLRAG_00670 1176 Uncharacterized conserved protein Yral CAETHG_3911 CUU_cl8020 CLRAG_00620 1177 Yipl domain-containing protein CAETHG_3916 CUU_cl8070 CLRAG_00580 1178 SatD family protein (SatD) CAETHG_3926 CUU_cl8180 CLRAG_00500 1179 SatD family protein (SatD) CAETHG_3927 CUU_cl8190 CLRAG_00490 1180 Protein of unknown function (DUF3307) CAETHG_3928 CUU_cl8200 CLRAG_00480 1181 EamA-like transporter family protein CAETHG_3929 CUU_cl8210 CLRAG_00470 1182 hypothetical protein CAETHG_3930 CUU_cl8220 CLRAG_00390 1183 Uncharacterized membrane protein CAETHG_3931 CUU_cl8230 CLRAG_00380 1184 hypothetical protein CAETHG_3946 CUU_cl8390 CLRAG_00290 1185 hypothetical protein CAETHG_3947 CUU_cl8400 CLRAG_00280 1186 hypothetical protein CAETHG_3948 CUU_cl8410 CLRAG_00270 1187 hypothetical protein CAETHG_3950 CUU_cl8430 CLRAG_00250 1188 hypothetical protein CAETHG_3955 CUU_cl8480 CLRAG_00200 1189 Protein A of glucose-inhibited fission CAETHG_3958 CUU_cl8510 CLRAG_00130 1190 protein of unknown function (DUF2935) CAETHG_3971 CUU_cl8630 CLRAG_00020 1191 hypothetical protein 2.7.4.12, 2.7.4.9 CAETHG_3972 CUU_cl8640 CLRAG_00010 1192 hypothetical protein CAETHG_3975 CUU_c34960 CLRAG_26220 1193 hypothetical protein CAETHG_3982 CUU_cl8680 CLRAG_16680 1194 hypothetical protein CAETHG_3983 CUU_cl8690 CLRAG_16670 1195 hypothetical protein CAETHG_3984 CUU_cl8700 CLRAG_16650 1196 protein of unknown function (DUF4397) CAETHG_3992 CUU_cl8730 CLRAG_16560 1197 hypothetical protein CAETHG_4006 CUU_cl8830 CLRAG_16420 1198 Uncharacterized membrane-bound YitT protein containing DUF161 and DUF2179 domains CAETHG_4049 CUU_cl9150 CLRAG_39900 1199 hypothetical protein CAETHG_4051 CUU_cl9170 CLRAG_39880 1200 hypothetical protein CAETHG_4053 CUU_cl9180 CLRAG_39870 1201 Immunity protein 22 CAETHG_4059 CUU_cl9240 CLRAG_39830 1202 hypoxanthine phosphoribosyltransferase 2.4.2.22, 2.4.2.7, 2.4.2.8 CAETHG_1290 CUU_c33920 CLRAG_14070 1203 hypoxanthine phosphoribosyltransferase 2.4.2.22, 2.4.2.7, 2.4.2.8 CAETHG_1988 CUU_c41540 CLRAG_04670 1204 cyclase CAETHG_3264 CUU_cll730 CLRAG_11810 1205 glutamine amidotransferase CAETHG_3261 CUU_cll700 CLRAG_11840 1206 imidazoleglycerophosphate dehydratase 4.2.1.19 CAETHG_3260 CUU_cll690 CLRAG_11850

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1207 imidazolone propionase 3.5.2.7 CAETHG_0233 CUU_c21470 CLRAG_31030 1208 indole-3-glycerophosphate synthase 4.1.1.48 CAETHG_3704 CUU_cl6100 CLRAG_33070 1209 IMP dehydrogenase 1.1.1.205 CAETHG_1571 CUU_c37180 CLRAG_36620 1210 iron(metal)-dependent repressor DtxR family CAETHG_1335 CUU_c34350 CLRAG_17700 1211 [FeFeJ-hydrogenase H-cluster maturation GTPase HydF CAETHG_2063 CUU_c42380 CLRAG_05500 1212 epoxyqueuosine reductase CAETHG_1774 CUU_c39290 CLRAG_21500 1213 beta-aspartyl dipeptidase (metallo-type) 3.4.11.1, 3.4.11.2, 3.4.13.3, 3.4.11.23 CAETHG_0748 CUU_c26670 CLRAG_08540 1214 Isoleucyl-tRNA synthetase CAETHG_2292 CUU_cO189O CLRAG_27490 1215 ketopantoate reductase 1.1.1.169 CAETHG_0118, CAETHG_2966 CLJU_cO872O, CUU_c20360 CLRAG_25930 1216 2-dehydropantoate-2-reductase CAETHG_3877 CUU_cl7690 CLRAG_01040 1217 L-arabinose isomerase 5.3.1.4 CAETHG_2228 CUU_cO12OO CLRAG_30220 1218 L-aspartate oxidase CAETHG_0502 CUU_c24420 CLRAG_25150 1219 1_-ribulose-5-phosphate-4-epimerase CAETHG_2229 CUU_c01210 CLRAG_30210 1220 L-serine dehydratase 4.3.1.17, 4.3.1.15, 4.3.1.19, 4.2.1.13 CAETHG_1224 CUU_c33250 CLRAG_15010 1221 L-serine dehydratase 4.3.1.17, 4.3.1.15, 4.3.1.19, 4.2.1.13 CAETHG_1225 CUU_c33260 CLRAG_15000 1222 E-seryl-tRNA(5ec)-seleniumtransferase CAETHG_2839 CUU_c07470, CUU_c27710 CLRAG_32220 1223 L-threonine aldolase 4.1.2.5 CAETHG_0686 CUU_c26170 CLRAG_04250 1224 threonine phosphate decarboxylase 4.1.1.81 CAETHG_1128 CUU_c32000 CLRAG_02630 1225 LemA protein CAETHG_0069 CUU_cl9890 CLRAG_39190 1226 leucyl tRNA synthetase CAETHG_2377 CLJU_cO275O CLRAG_28350 1227 LexA repressor CAETHG_0188 CLJU_c21030 CLRAG_18990 1228 Predicted dehydrogenase 1.1.1.18 CAETHG_1307 CUU_c34090 CLRAG_14240 1229 lipoic acid synthetase CAETHG_1220 CUU_c33210 CLRAG_15050 1230 Apoenzyme LL- diaminopimelate aminotransferase 2.6.1.83 CAETHG_3510 CUU_cl4280 CLRAG_09600 1231 large ribosomal subunit protein L10 CAETHG_1957 CUU_c41140 CLRAG_23330 1232 Large ribosomal subunit protein L11P CAETHG_1959 CUU_c41160 CLRAG_23350 1233 Large ribosomal subunit protein L13P CAETHG_1914 CUU_c40710 CLRAG_22900 1234 Large ribosomal subunit protein L14P CAETHG_1937 CUU_c40940 CLRAG_23130 1235 Large ribosomal subunit protein L15P CAETHG_1928 CUU_c40850 CLRAG_23040 1236 Large ribosomal subunit protein L16P CAETHG_1940 CUU_c40970 CLRAG_23160 1237 Large ribosomal subunit protein L17P CAETHG_1919 CUU_c40760 CLRAG_22950 1238 Large ribosomal subunit protein L20P CAETHG_1344 CUU_c34440 CLRAG_14520 1239 Large ribosomal subunit protein L22P CAETHG_1942 CUU_c40990 CLRAG_23180 1240 Large ribosomal subunit protein L24P CAETHG_1936 CUU_c40930 CLRAG_23120 1241 Large ribosomal subunit protein L27P CAETHG_2830 CUU_cO738O CLRAG_26460 1242 large ribosomal subunit protein L28 CAETHG_3348 CUU_cl2670 CLRAG_11140 1243 Large ribosomal subunit protein L29P CAETHG_1939 CUU_c40960 CLRAG_23150 1244 large ribosomal subunit protein L30 CAETHG_1929 CUU_c40860 CLRAG_23050 1245 Large ribosomal subunit protein L32P CAETHG_3361 CUU_cl2800 CLRAG_11010

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1246 large ribosomal subunit protein L33 CAETHG_1962 CUU_c41190 CLRAG_23380 1247 large ribosomal subunit protein L34 CAETHG_2123 CUU_c42970 CLRAG_25780 1248 Large ribosomal subunit protein L36P CAETHG_1924 CUU_c40810 CLRAG_23000 1249 large ribosomal subunit protein L4 CAETHG_1946 CUU_c41030 CLRAG_23220 1250 large ribosomal subunit protein L9 CAETHG_2098 CUU_c42730 CLRAG_25540 1251 lysine: proton symporter of the AAT family CAETHG_0271, CAETHG_0496 CLJU_c24360, CUU_c21810 CLRAG_31350 1252 DNA-binding transcriptional regulator of the LysR family CAETHG_3878 CLJU_cl7700 CLRAG_01030 1253 class II lysyl-tRNA synthetase CAETHG_1982 CUU_c41480 CLRAG_04610 1254 Sugar phosphate permease CAETHG_3582 CUU_cl4820 CLRAG_20290 1255 Malate/lactate/ureidoglycolate dehydrogenase of the LDH2 family 1.1.1.37 CAETHG_2689 CUU_c05920 CLRAG_07150 1256 [acyl group transfer protein]-5- malonyltransferase CAETHG_2048 CUU_c42170 CLRAG_05280 1257 Μη-containing catalase CAETHG_3970 CUU_cl8620 CLRAG_00030 1258 manganese dependent inorganic pyrophosphatase 3.6.1.1 CAETHG_3137 CUU_cl0470 CLRAG_12900 1259 mannose-Gphosphate guanylyltransferase 2.7.7.22 CAETHG_2296 CUU_c01930 CLRAG_27530 1260 Mannose-6-phosphate isomerase type 1 5.3.1.8 CAETHG_1790 CUU_c39450 CLRAG_21660 1261 DNA-binding transcriptional regulator of the MerR family CAETHG_0698 CUU_c26220 CLRAG_04300 1262 HDIG domain-containing protein CAETHG_1005 CLJU_c30060 CLRAG_15690 1263 methylenetetra hydrofolate dehydrogenase (H ADP+)/methene yltetra hydrofolate clohydrol aza 1.5.1.5 CAETHG_1616 CUU_c37630 CLRAG_37040 1264 methionine adenosyltransferase 2.5.1.6 CAETHG_0419, CAETHG_2358 CLJU_c23550, CUU_cO258O CLRAG_28180 1265 methionylaminopeptidase 3.4.11.1, 3.4.11.2, 3.4.13.3, 3.4.11.23 CAETHG_1486 CUU_c35780 CLRAG_06310 1266 5- methyltetrahydrofolate homocysteine methyltransferase 2.1.1.13, 2.1.1.14 CAETHG_2755 CUU_c06650 CLRAG_18450 1267 5- methyltetrahydrofolate homocysteine methyltransferase CAETHG_2843, CAETHG_2848 CLJU_cO755O, CUU_cO75OO CLRAG_34280 1268 methionyl-tRNA formyltransferase CAETHG_3339 CUU_cl2570 CLRAG_11230 1269 methionyl-tRNA synthetase CAETHG_2275 CUU_c01730 CLRAG_27330 1270 methyl acceptor sensor chemotaxis transducer CAETHG_0308 CUU_c22100 CLRAG_31620 1271 methyl acceptor sensor chemotaxis transducer with Cache sensor CAETHG_0077 CUU_cl9970 CLRAG_39070 1272 methyl acceptor sensor chemotaxis transducer with Cache sensor CAETHG_0229 CUU_c21430 CLRAG_30990 1273 methyl acceptor sensor chemotaxis transducer with Cache sensor CAETHG_0350 CUU_c22880 CLRAG_01910 1274 methyl acceptor sensor chemotaxis transducer with Cache sensor CAETHG_0542, CAETHG_1048 CUU_c24770, CLJU_c30430 CLRAG_18050 1275 methyl acceptor sensor chemotaxis transducer with Cache sensor CAETHG_2402 CUU_cO287O CLRAG_28470 1276 methyl acceptor sensor chemotaxis transducer with Cache sensor CAETHG_2997 CLJU_cO9O3O CLRAG_13990 1277 methyl acceptor sensor chemotaxis transducer with Cache sensor CAETHG_3106 CUU_cl0160 CLRAG_13210 1278 methyl acceptor sensor chemotaxis transducer with Cache sensor CAETHG_3430 CUU_cl3460 CLRAG_10330 1279 methyl acceptor sensor CAETHG_3459 CUU_cl3760 CLRAG_10080

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chemotaxis transducer with Cache sensor 1280 methyl acceptor sensor chemotaxis transducer with Cache sensor CAETHG_3466 CUU_cl3830 CLRAG_10010 1281 methyl acceptor sensor chemotaxis transducer with Cache sensor CAETHG_4020 CUU_cl8880 CLRAG_40120 1282 methylaspartate ammonia lyase CAETHG_1904 CUU_c40610 CLRAG_22800 1283 methylated-DNA-[protein]-cysteine-5methyltransferase CAETHG_3895 CUU_cl7870 CLRAG_00790 1284 5,10-methylenetetrahydrofolate reductase 1.5.1.20 CAETHG_1614 CUU_c37610 CLRAG_37020 1285 Methyl glycol synthase CAETHG_2822 CUU_c07300 CLRAG_26540 1286 methyltetrahydrofolate-corrinoid-containing iron-sulfur protein-Co-methyltransferase CAETHG_1609 CUU_c37560 CLRAG_36970 1287 adenosylhomocysteine nucleosidase 3.2.2.16, 3.2.2.9 CAETHG_3160 CUU_clO7OO CLRAG_12640 1288 Protein containing a methyltransferase domain CAETHG_1633 CUU_c38050 CLRAG_37420 1289 Mo-nitrogenase, MoFe protein, precursor of the NifD subunit CAETHG_2570 CUU_cO493O CLRAG_38320 1290 nitrogenase, molybdenum-iron-containing protein, beta chain CAETHG_2571 CUU_cO494O CLRAG_38330 1291 Modular scaffolding protein NifU containing FeS cluster CAETHG_3294 CUU_cl2120 CLRAG_11680 1292 protein A synthesis molybdoptering guanine dinucleotide CAETHG_0227 CUU_c21410 CLRAG_30970 1293 molybdopterin adenylate transferase CAETHG_0574 CUU_c25060 CLRAG_17720 1294 protein B biosynthesis molybdoptering guanine dinucleotide 1.1.99.33 CAETHG_2792 CUU_c07010 CLRAG_18860 1295 molybdopterinmolybdotransferase 1.1.99.33 CAETHG_2791 CUU_cO7OOO CLRAG_18850 1296 ABC-transporter of monosaccharides, ATP- CUT2 family binding protein CAETHG_1384 CUU_c34860 CLRAG_26100 1297 ribose transport system, ATP-binding protein CAETHG_2236 CUU_cO127O CLRAG_30150 1298 ABC monosaccharide transporter, membrane protein of the CUT2 family CAETHG_1382 CUU_c34840 CLRAG_26080 1299 simple carbohydrate transport system, permease protein CAETHG_1383 CUU_c34850 CLRAG_26090 1300 ABC monosaccharide transporter, substrate-binding protein of the CUT2 family CAETHG_1385 CUU_c34870 CLRAG_26110 1301 dsDNA-specific endonuclease/ATPase MutS2 CAETHG_3607 CUU_cl5050 CLRAG_24320 1302 N-acetyl-gamma-glutamylphosphate reductase 1.2.1.38 CAETHG_0241 CUU_c21540 CLRAG_31100 1303 N-acetylglutamate kinase 2.7.2.8 CAETHG_0239 CUU_c21520 CLRAG_31080 1304 N-acetylanhydromuramil-E-alanine amidase AmpD 3.5.1.28 CAETHG_1654 CUU_c32580 CLRAG_29450 1305 N-acetylmuramoyl-E-alanine amidase 3.5.1.28 CAETHG_1765 CUU_c39200 CLRAG_21350 1306 N-acetylmuramoyl-E-alanine amidase CAETHG_1912 CUU_c40690 CLRAG_22880 1307 N-acyl-O-amino acid deacylase CAETHG_0452 CUU_c23870 CLRAG_17300 1308 amido hydrolase CAETHG_2511 CUU_c04420 CLRAG_37750 1309 N-carbamoyl-E-amino acid hydrolase 3.5.1.6 CAETHG_1498 CUU_c35910 CLRAG_06410 1310 N-formylglutamate hydrolase CAETHG_0505 CUU_c24450 CLRAG_30120 1311 4-hydroxybutyrate dehydrogenase 1.1.1.1 CAETHG_1741 CUU_c38930 CLRAG_21110 1312 NAD-dependent deacetylase CAETHG_2239 CUU_cO132O CLRAG_26980 1313 isocitrate dehydrogenase (NAD+) 1.1.1.286, 1.1.1.41 CAETHG_2753 CUU_c06630 CLRAG_18430 1314 malate dehydrogenase (oxaloacetate- decarboxylating) 1.1.1.37, 1.1.1.40, 1.1.1.38, 4.1.1.3, CAETHG_1702, CAETHG_2478 CUU_c38460, CUU_cO416O CLRAG_26900

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1.1.1.39 1315 NAD(P)-dependent hydrogenase containing an iron atom, catalytic subunit CAETHG_3569 CUU_cl4700 CLRAG_20490 1316 NADH quinone oxidoreductase, subunit E CAETHG_3571 CUU_cl4720 CLRAG_20470 1317 NAD(P)H-dependent nitrate reductase, catalytic subunit 1.7.7.2 CAETHG_0437 CUU_c23730 CLRAG_17440 1318 NAD(P)H-dependent nitrate reductase, diaphorase subunit CAETHG_0435 CUU_c23710 CLRAG_17460 1319 NAD(P)H-dependent nitrate reductase, iron-sulfur subunit CAETHG_0436 CUU_c23720 CLRAG_17450 1320 NADH quinone oxidoreductase, subunit E 1.12.1.4, 1.1.99.33 CAETHG_2794 CLJU_cO7O3O CLRAG_18880 1321 NADH quinone oxidoreductase, subunit F 1.12.1.4, 1.1.99.33 CAETHG_1577, CAETHG_3570, CAETHG_2795 CUU_cO7O4O, CUU_cl4710 CLRAG_20480 1322 protein containing a domain with a 4Fe4S dicluster 1.12.1.4, 1.1.99.33 CAETHG_2796 CLJU_cO7O5O CLRAG_18900 1323 NAD+-diphosphatase CAETHG_2205 CUU_cOO91O CLRAG_19670 1324 glutamate dehydrogenase (NADP+) CAETHG_2367 CUU_c02660 CLRAG_28260 1325 NADPH-dependent FMN reductase CAETHG_0974 CUU_c29750 CLRAG_35750 1326 glutamate synthase (NADPH/NADH), small chain CAETHG_0477 CUU_c24190 CLRAG_24880 1327 carbon monoxide dehydrogenase, catalytic subunit CAETHG_1621 CUU_c37670 CLRAG_37080 1328 nicotinamidase/pyrazinamidase 3.5.1.19 CAETHG_0378 CUU_c23150 CLRAG_01660 1329 NAD+ kinase 2.7.1.23 CAETHG_3207 CUU_clll80 CLRAG_12280 1330 nicotinate phosphoribosyltransferase 2.4.2.11 CAETHG_3427 CUU_cl3430 CLRAG_10360 1331 nicotinate nucleotide adenylate transferase 2.7.7.1, 2.7.7.18 CAETHG_2832 CLJU_c07400 CLRAG_26440 1332 molybdenum transport protein CAETHG_1634 CUU_c38070 CLRAG_37440 1333 nicotinate nucleotide pyrophosphorylase [carboxylating] CAETHG_0501 CUU_c24410 CLRAG_25140 1334 nicotinate nucleotide dimethylbenzimidazolephos phoribosyltransferase 2.4.2.21 CAETHG_1122 CUU_c31940 CLRAG_02570 1335 nitrogen-regulating protein of the P-11 family CAETHG_2091, CAETHG_2468 CLJU_c04050, CUU_c42650 CLRAG_05670 1336 nitrogen-regulating protein of the P-11 family CAETHG_2568 CUU_c04910 CLRAG_38300 1337 protein regulating nitrogen metabolism, P-11 family CAETHG_2569 CUU_c04920 CLRAG_38310 1338 nitrogenase, molybdenum-iron protein NifN CAETHG_2573 CUU_c04960 CLRAG_38350 1339 nitrogenase, iron-containing protein NifH 1.18.6.1 CAETHG_0368, CAETHG_0375 CLJU_c23050, CUU_c23120 CLRAG_01760 1340 nitrogenase, iron-containing protein NifH 1.18.6.1 CAETHG_0417, CAETHG_2567 CLJU_c23530, CUU_c04900 CLRAG_38290 1341 nitrogenase, protein for the synthesis of molybdenum cofactor NifE CAETHG_0374 CUU_c23110 CLRAG_01700 1342 nitrogenase, protein for the synthesis of molybdenum cofactor NifE CAETHG_2572 CUU_c04950 CLRAG_38340 1343 nitroreductase CAETHG_0934 CUU_c29400 CLRAG_35400 1344 simple sugar transport system, ATP-binding protein CAETHG_0998 CUU_c29990 CLRAG_35990 1345 ABC-nucleoside transporter, ATP- CUT2 family binding protein CAETHG_1808 CUU_c39620 CLRAG_21810 1346 simple carbohydrate transport system, permease protein CAETHG_0996, CAETHG_1806 CLJU_c29970, CUU_c39600 CLRAG_35970 1347 simple carbohydrate transport system, permease protein CAETHG_0997 CUU_c29980 CLRAG_35980 1348 ABC nucleoside transporter, membrane protein CAETHG_1807 CUU_c39610 CLRAG_21800

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1349 basic membrane protein A CAETHG_0999 CUU_c30000 CLRAG_36000 1350 nucleoside binding protein CAETHG_1809 CUU_c39630 CLRAG_21820 1351 ATP-dependent Lon protease CAETHG_1470 CUU_c35620 CLRAG_06150 1352 nucleoside triphosphatase CAETHG_3826 CUU_cl7140 CLRAG_34000 1353 Antitermination factor NusA CAETHG_3395 CUU_cl3120 CLRAG_10670 1354 Antitermination factor NusB CAETHG_3201 CUU_clll20 CLRAG_12340 1355 O-acetylhomoserine sulfhydrolase 2.5.1.48, 2.5.1.-, 4.2.99.8, 4.2.99.10, 2.5.1.49, 4.2.99.9 CAETHG_2754 CUU_c06640 CLRAG_18440 1356 N6-E-threonylcarbamoyladenine synthase CAETHG_1595 CUU_c37400 CLRAG_36840 1357 oligopeptidase F. Metallopeptidase. MEROPS family М03В CAETHG_4039 CUU_cl9050 CLRAG_39980 1358 putative transporter of ORT family oligopeptides CAETHG_3477 CUU_cl3940 CLRAG_09250 1359 ornithine carbamoyltransferase 2.1.3.3 CAETHG_0591 CUU_c25230 CLRAG_03580 1360 orotate phosphoribosyltransferase 2.4.2.10 CAETHG_1476 CUU_c35680 CLRAG_06210 1361 orotidine 5'-phosphate decarboxylase 4.1.1.23 CAETHG_1479 CUU_c35710 CLRAG_06240 1362 oxygen-independent coproporphyrinogen 3 oxidase CAETHG_2888 CUU_cO795O CLRAG_25430 1363 tripeptidaminopeptidase CAETHG_0005, CAETHG_0008 CLJU_cl9290, CUU_cl9310 CLRAG_39770 1364 peptide chain releasing factor 1 CAETHG_2331 CUU_c02260 CLRAG_27860 1365 peptide chain releasing factor 3 CAETHG_1685 CUU_c38280 CLRAG_20750 1366 peptide deformylase CAETHG_0293 CUU_c21960 CLRAG_31510 1367 peptide deformylase CAETHG_3338, CAETHG_3446 CLJU_cl3640, CUU_cl2560 CLRAG_11240 1368 peptide deformylase CAETHG_3892 CUU_cl7840 CLRAG_00870 1369 predecessor ErfK-family peptidoglycan transpeptidases YbiS-YhnG CAETHG_3681 CUU_cl5730 CLRAG_32890 1370 peptidylprolyl cis-trans isomerase B (cyclophilin B) CAETHG_0351 CUU_c22890 CLRAG_01900 1371 peptidyl-tRNA hydrolase of the PTH1 family CAETHG_2002 CUU_c41730 CLRAG_04860 1372 phage shock protein A (PspA) family protein CAETHG_2260 CUU_c01540 CLRAG_27200 1373 phenylalanyl-tRNA synthetase, beta subunit CAETHG_1341 CUU_c34410 CLRAG_14490 1374 phenylalanyl-tRNA synthetase, alpha subunit CAETHG_1342 CUU_c34420 CLRAG_14500 1375 ABC phosphate transporter, ATP-binding protein of the PhoT family CAETHG_3324 CUU_cl2420 CLRAG_11380 1376 ABC phosphate transporter, PhoT family membrane protein 1 CAETHG_3322 CUU_cl2400 CLRAG_11400 1377 ABC phosphate transporter, PhoT family membrane protein 2 CAETHG_3323 CUU_cl2410 CLRAG_11390 1378 ABC phosphate transporter, substrate-binding protein of the PhoT family CAETHG_3321 CUU_cl2390 CLRAG_11410 1379 phosphate:acyl-[acyl carrier protein group]-acyltransferase 2.3.1.15 CAETHG_3362 CUU_cl2810 CLRAG_11000 1380 phosphatidylserine decarboxylase 4.1.1.65 CAETHG_2188 CLJU_cOO71O CLRAG_19870 1381 CDP-diacylglycerol-serol-Ophosphatidyltransferase 2.7.8.8 CAETHG_2406 CUU_c02910 CLRAG_28510 1382 Phospho-N- acetylmuramoylpentapeptide transferase 2.7.8.13 CAETHG_3149 CUU_cl0590 CLRAG_12750 1383 phosphoenolpyruvate carboxykinase (ATP) 4.1.1.49 CAETHG_2721 CUU_c06210 CLRAG_07490 1384 phosphotransferase system, enzyme 1, Ptsl 2.7.1.69 CAETHG_1896 CUU_c40530 CLRAG_22720

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1385 phosphoglucomutase 5.4.2.10, 5.4.2.2 CAETHG_1320 CUU_c34210 CLRAG_14360 1386 phosphoglucosamine mutase 5.4.2.10, 5.4.2.2 CAETHG_1887 CUU_c40440 CLRAG_22630 1387 D-3-phosphoglycerate dehydrogenase 1.1.1.95 CAETHG_1176 CUU_c32780 CLRAG_15580 1388 phosphoglycerate kinase 2.7.2.3 CAETHG_1759 CUU_c39140 CLRAG_21290 1389 phosphoglycerate mutase 5.4.2.11 CAETHG_1757 CUU_c39120 CLRAG_21270 1390 phosphoglucomutase 5.4.2.8 CAETHG_0898 CUU_c29060 CLRAG_35060 1391 Hydroxymethylpyrimidine/phosphomethylpyrimidine kinase 2.7.1.49, 2.7.4.7 CAETHG_1202 CLJU_c33040 CLRAG_15290 1392 Phosphopanthetheine adenylate transferase 2.7.7.3 CAETHG_3353 CUU_cl2720 CLRAG_11090 1393 phosphopantothenoylcysteine decarboxylase/phosphopantothenate cysteine ligase 4.1.1.36, 6.3.2.5 CAETHG_3336 CUU_cl2540 CLRAG_11260 1394 phosphopentomutase 5.4.2.2, 5.4.2.7 CAETHG_3924 CUU_cl8150 CLRAG_00520 1395 phosphoribosyl-AMP cyclohydrolase CAETHG_3265 CUU_cll740 CLRAG_11800 1396 phosphoribosyl-ATP pyrophosphatase 3.5.4.19, 3.6.1.31 CAETHG_3266 CUU_cll750 CLRAG_11790 1397 phosphoribosylamine glycine ligase 6.3.4.13 CAETHG_2954 CLJU_c08600 CLRAG_07890 1398 phosphoribosylaminimidazole succinocarboxy midsynthase 6.3.2.6 CAETHG_2949 CUU_c08550 CLRAG_07940 1399 phosphoribosylanthranilate isomerase 5.3.1.24 CAETHG_3705 CUU_cl6110 CLRAG_33080 1400 phosphoribosylformylglycinamidine cycloligation for 6.3.3.1 CAETHG_2951 CUU_c08570 CLRAG_07920 1401 phosphoribosylformylglycinamidine synthase 6.3.5.3 CAETHG_3245 CUU_cll540 CLRAG_11910 1402 Hydrolase TIGR01490 of the HAD superfamily, subfamily IB 3.1.3.3 CAETHG_3031 CUU_c09360 CLRAG_13740 1403 phosphate acetyltransferase 2.3.1.8 CAETHG_3358 CUU_cl2770 CLRAG_11040 1404 GH3 auxin-responsive promoter CAETHG_3993 CUU_cl8740 CLRAG_16550 1405 Polyferredoxin CAETHG_0511 CUU_c24510 CLRAG_30060 1406 polyribonucleotidyl transferase CAETHG_3404 CLJU_cl3210 CLRAG_10580 1407 porphobilinogen synthase 4.2.1.24 CAETHG_1124 CUU_c31960 CLRAG_02590 1408 positive regulator sigma(E), RseC/MucC CAETHG_3226 CUU_cll350 CLRAG_12100 1409 K+-transporting ATPase, chain A CAETHG_1801 CUU_c39560 CLRAG_21760 1410 K+-transporting ATPase, chain B CAETHG_1800 CUU_c39550 CLRAG_21750 1411 K+-transporting ATPase, chain C CAETHG_1799 CUU_c39540 CLRAG_21740 1412 precorrin-2/cobalt factor-2 C20- methyltransferase 2.1.1.151, 2.1.1.130 CAETHG_1117 CUU_c31890 CLRAG_02520 1413 precorrin-2- dehydrogenase/sirohydrochlorine ferrochelatase 2.1.1.107, 1.3.1.76, 4.99.1.4 CAETHG_1127 CUU_c31990 CLRAG_02620 1414 precorrin-6U-C5,15-methyltransferase (decarboxylating) 2.1.1.132 CAETHG_1119 CLJU_c31910 CLRAG_02540 1415 prephenate dehydrogenase 1.3.1.52, 1.3.1.13, 1.3.1.43, 1.3.1.12 CAETHG_0909 CUU_c29170 CLRAG_35170 1416 phosphatidylglycerol:prolipoprotein diacylglycerol transferase CAETHG_2935 CUU_c08410 CLRAG_08040 1417 p rol yl-tRN K-si ntetase CAETHG_1694 CUU_c38360 CLRAG_20830 1418 ethanolamine utilization protein EutP CAETHG_3900 CUU_cl7920 CLRAG_00710 1419 hypothetical protein CAETHG_0742 CUU_c26610 CLRAG_08480 1420 hypothetical protein CAETHG_2546 CLJU_c04740 CLRAG_38120 1421 preprotein translocase, SecA subunit CAETHG_2364 CUU_c02630 CLRAG_28230 1422 protein translocase, secY/sec61 alpha subunit CAETHG_1927 CLJU_c40840 CLRAG_23030

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1423 protein tyrosine phosphatase CAETHG_2335 CUU_c02300 CLRAG_27900 1424 PTS system, fructose specific PS component 2.7.1.69 CAETHG_0142 CUU_c20590 CLRAG_19390 1425 PA component of the PTS system of the Fru family 2.7.1.69 CAETHG_0676 CUU_c26070 CLRAG_04160 1426 PTS system, fructose-specific IIE3-like component CAETHG_0674 CUU_c26050 CLRAG_04140 1427 PTS system, fructose-specific non-similar component 2.7.1.69 CAETHG_0675 CUU_c26060 CLRAG_04150 1428 hypothetical protein CAETHG_2387 CUU_c02850, CUU_cl5580 CLRAG_28450 1429 purine nucleoside phosphorylase 2.4.2.23, 2.4.2.2, 2.4.2.15, 2.4.2.4, 2.4.2.1 CAETHG_0160 CUU_c20750 CLRAG_19250 1430 purine operon repressor, PurR CAETHG_2009 CUU_c41800 CLRAG_04930 1431 Substrate-specific CoA activase enzyme, putative CAETHG_1482 CUU_c35740 CLRAG_06270 1432 16S rRNA processing protein RimM CAETHG_3373 CUU_cl2910 CLRAG_10890 1433 Benzoyl-CoA reductase subunit/2- hydroxyglutaryl-CoA dehydratase, BcrC/BadD/HgdB CAETHG_0196 CUU_c21100 CLRAG_30680 1434 Benzoyl-CoA reductase subunit/2- hydroxyglutaryl-CoA dehydratase, BcrC/BadD/HgdB CAETHG_1484 CUU_c35760 CLRAG_06290 1435 DNA-3-methyladenine glycosylase CAETHG_2298 CLJU_cO195O CLRAG_27550 1436 small ribosomal subunit protein S1 CAETHG_0848 CUU_c28540 CLRAG_34610 1437 Small ribosomal subunit protein S21P CAETHG_2898 CUU_c08040 CLRAG_08320 1438 molecular chaperone Hsp33 CAETHG_1356 CUU_c34600 CLRAG_14680 1439 4-hydroxybenzoate polyprenyltransferase CAETHG_3414 CUU_cl3310 CLRAG_10480 1440 electron transport protein HydN 1.12.1.4, 1.1.99.33 CAETHG_2797 CUU_c07060 CLRAG_18910 1441 Large ribosomal subunit protein L21P CAETHG_2828 CUU_c07360 CLRAG_26480 1442 8-oxo-dGTP diphosphatase CAETHG_3520, CAETHG_3545 CUU_cl4320 CLRAG_09720 1443 N-glycosylase/DNA lyase CAETHG_1579 CUU_c37230 CLRAG_36670 1444 putative substrate-binding protein of the transport system hydroxymethylpyrimidine CAETHG_0607 CUU_c25380 CLRAG_03660 1445 lipoprotein release system permease protein CAETHG_2657 CUU_c05650 CLRAG_06870 1446 iron complex transport system, substrate-binding protein CAETHG_3822, CAETHG_3838 CUU_cl7250, CUU_cl7100 CLRAG_33970 1447 iron complex transport system, substrate-binding protein CAETHG_3827 CUU_cl7150 CLRAG_34010 1448 iron complex transport system, substrate-binding protein CAETHG_3833 CUU_cl7200 CLRAG_34200 1449 ABC-2 type transport system, ATP-binding protein CAETHG_0042, CAETHG_3942 CUU_cl8350, CUU_cl9650 CLRAG_39490 1450 ABC-2 type transport system, ATP-binding protein CAETHG_0354, CAETHG_3008 CUU_c09140, CLJU_c37410, CUU_c22920 CLRAG_01870 1451 ABC-2 type transport system, ATP-binding protein CAETHG_0388 CUU_c23250 CLRAG_01480 1452 ABC-2 type transport system, ATP-binding protein CAETHG_0531 CUU_c24660 CLRAG_18170 1453 ABC-2 type transport system, ATP-binding protein CAETHG_0580 CUU_c25120 CLRAG_03460 1454 transport system hydroxymethylpyrimidine, putative CAETHG_0609 CUU_c25400 CLRAG_03680

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ATP binding protein 1455 Transport system multiple ABC-type drug resistance, ATPase component CAETHG_0640 CUU_c25710 CLRAG_03910 1456 ABC transport system, proposed ATP binding protein CAETHG_0646 CUU_c25770 CLRAG_04000 1457 ABC-2 type transport system, ATP-binding protein CAETHG_0658 CUU_c25890 CLRAG_04030 1458 spermidine/putrescine transport system, putative ATP-binding protein CAETHG_0683 CUU_c26140 CLRAG_04220 1459 Transport system of the NitT/TauT family, ATP-binding protein Z.A.1.17 CAETHG_0732 CUU_c26510 CLRAG_08390 1460 ATP-binding Fe-S cluster assembly protein CAETHG_0775, CAETHG_1631 CLJU_c37940, CUU_c26910 CLRAG_37330 1461 ABC-2 type transport system, ATP-binding protein CAETHG_0791 CUU_c27070 CLRAG_08830 1462 Transport system multiple ABC-type drug resistance, ATPase component CAETHG_0799 CUU_c27130 CLRAG_20100 1463 ABC transport system, proposed ATP binding protein CAETHG_0804, CAETHG_2218, CAETHG_2870, CAETHG_2861 CLJU_c01070, CLJU_cO768O, CUU_c07780, CUU_c27190 CLRAG_20040 1464 ABC transport system, proposed ATP binding protein CAETHG_1016 CUU_c30160 CLRAG_39150 1465 ABC-2 type transport system, ATP-binding protein CAETHG_1199 CUU_c33010 CLRAG_15320 1466 ABC-2 type transport system, ATP-binding protein CAETHG_1427 CUU_c35190 CLRAG_05700 1467 ABC-2 type transport system, ATP-binding protein CAETHG_1437 CUU_c35280 CLRAG_05810 1468 Transport system of the NitT/TauT family, ATP-binding protein CAETHG_1443 CUU_c35340 CLRAG_05870 1469 ATP-binding cassette subfamily F member 3 CAETHG_1582 CUU_c37260 CLRAG_36700 1470 ABC-2 type transport system, ATP-binding protein CAETHG_1584 CUU_c37280 CLRAG_36720 1471 ABC transport system, proposed ATP binding protein CAETHG_1713 CUU_c38630 CLRAG_20950 1472 ABC transport system, proposed ATP binding protein CAETHG_1847, CAETHG_3515 CUU_c40000, CUU_cl4420 CLRAG_22240 1473 ATPase components of ABC transporters with duplicated ATPase domains CAETHG_1855 CUU_c40060 CLRAG_22320 1474 bacitracin transport system, ATP-binding protein CAETHG_2195 CUU_cOO8OO CLRAG_19780 1475 ABC-2 type transport system, ATP-binding protein CAETHG_2530, CAETHG_2868 CUU_cO458O, CUU_c07760 CLRAG_37940 1476 D-methionine transport system, ATP-binding protein CAETHG_2532, CAETHG_2724 CUU_c04600, CUU_cO628O CLRAG_37960 1477 ATP-binding protein system release of lipoproteins CAETHG_2658 CUU_cO566O CLRAG_06880 1478 bacitracin transport system, ATP-binding protein CAETHG_2745 CUU_cO649O CLRAG_30410 1479 Transport system ABC-type nitrate/sulfonate/bicarbonate, ATPase component CAETHG_2976 CUU_cO881O CLRAG_07680 1480 ABC-2 type transport system, ATP-binding protein CAETHG_3462 CUU_cl3790 CLRAG_10050 1481 ABC transport system, proposed ATP binding protein CAETHG_3506 CUU_cl4240 CLRAG_09560 1482 ABC transport system, proposed ATP binding protein CAETHG_3512 CUU_cl4300 CLRAG_09660 1483 ABC transport system, proposed CAETHG_3650, CUU_cl5490, CLRAG_00560

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ATP binding protein CAETHG_3918 CUU_cl8090 1484 iron complex transport system, ATP-binding protein CAETHG_3828 CUU_cl7160 CLRAG_34020 1485 macrolide transport system, ATP-binding/permease protein CAETHG_4036 CUU_cl9020 CLRAG_40020 1486 Subfamily B protein of proteins containing an ATP-binding cassette CAETHG_3620 CUU_cl5180 CLRAG_24170 1487 Subfamily B protein of proteins containing an ATP-binding cassette CAETHG_4025 CUU_cl8910 CLRAG_40060 1488 ABC-2 transport system permease protein CAETHG_0530 CUU_c24650 CLRAG_18180 1489 transport system hydroxymethylpyrimidine, putative permease protein CAETHG_0608 CUU_c25390 CLRAG_03670 1490 spermidine/putrescine transport system, putative permease protein CAETHG_0684 CUU_c26150 CLRAG_04230 1491 spermidine/putrescine transport system, putative permease protein CAETHG_0685 CUU_c26160 CLRAG_04240 1492 NitT/TauT family transport system, permease protein Z.A.1.17 CAETHG_0733 CUU_c26520 CLRAG_08400 1493 NitT/TauT family transport system, permease protein CAETHG_1444 CUU_c35350 CLRAG_05880 1494 ABC transport system, putative permease protein CAETHG_1846 CUU_c39990 CLRAG_22230 1495 bacitracin transport system, permease protein CAETHG_2194 CUU_cOO79O CLRAG_19790 1496 ABC transport system, putative permease protein CAETHG_2219 CUU_c01080 CLRAG_30320 1497 bacitracin transport system, permease protein CAETHG_2744 CUU_c06480 CLRAG_30420 1498 ABC transport system, putative permease protein CAETHG_2862 CUU_c07690 CLRAG_25220 1499 hypothetical protein CAETHG_3464 CUU_cl3810 CLRAG_10030 1500 ABC transport system, putative permease protein CAETHG_3507 CUU_cl4250 CLRAG_09570 1501 iron complex transport system, permease protein CAETHG_3825 CUU_cl7130 CLRAG_33990 1502 ABC transport system, putative permease protein CAETHG_3919 CUU_cl8100 CLRAG_00550 1503 ABC-2 transport system permease protein CAETHG_3943 CUU_cl8360 CLRAG_00310 1504 spermidine/putrescine transport system, putative substrate-binding protein CAETHG_0682 CUU_c26130 CLRAG_04210 1505 Subfamily B protein of proteins containing an ATP-binding cassette CAETHG_4024 CUU_cl8900 CLRAG_40070 1506 ABC-2 transport system permease protein CAETHG_0043 CUU_cl9660 CLRAG_39480 1507 acetaldehyde dehydrogenase (acetylation) CAETHG_1830 CUU_c39840 CLRAG_22090 1508 acetyl-CoA-C-acetyltransferase CAETHG_0427 CUU_c23630 CLRAG_17540 1509 Protein of the acetyltransferase family (GNAT) CAETHG_0216 CUU_c21300 CLRAG_30860 1510 Acetyltransferase domain-containing protein (GNAT) CAETHG_0923, CAETHG_3174 CLJU_c29300, CUU_cl0850 CLRAG_35310 1511 phosphinotricin acetyltransferase CAETHG_1060 CUU_c30550 CLRAG_08730 1512 Ribosomal protein acetylase S18 Riml CAETHG_1413 CUU_c35040 CLRAG_26300 1513 GNAT family N-acetylglutamate synthase CAETHG_1749 CUU_c39010 CLRAG_21190 1514 Ribosomal protein acetylase S18 Riml CAETHG_2735 CUU_c06400 CLRAG_30450 1515 Predicted nucleotide binding protein, sugar kinase/H5P70/actin superfamily CAETHG_0183 CUU_c20990 CLRAG_19030 1516 Substrate-specific CoA activase enzyme, putative CAETHG_1442 CUU_c35330 CLRAG_05860

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1517 acyl group transfer protein CAETHG_3363 CUU_cl2820 CLRAG_10990 1518 medium-chain acyl hydrolase-[acyl group transfer protein] CAETHG_2058 CLJU_c42340 CLRAG_05450 1519 Acyl-CoA dehydrogenase 1.3.1.44, 1.3.99.2 CAETHG_1787 CUU_c39420 CLRAG_21630 1520 acyl-CoA dehydrogenase 1.3.1.44, 1.3.99.2 CAETHG_1789 CLJU_c39440 CLRAG_21650 1521 Crotonobetainyl-CoA:carnitine-CoAtransferase CaiB CAETHG_1788 CUU_c39430 CLRAG_21640 1522 Surface polysaccharide-O- acyltransferase, integral membrane enzyme CAETHG_1301 CLJU_c34030 CLRAG_14180 1523 Fucose-4-O-acetylase CAETHG_1311 CUU_c34130 CLRAG_14280 1524 adenylate cyclase class 2 4.6.1.1 CAETHG_2381 CUU_c02800 CLRAG_28400 1525 ADP-ribosyl-[dinitrogen reductase]-hydrolase CAETHG_0078 CUU_cl9980 CLRAG_39060 1526 hypothetical protein CAETHG_0588 CUU_c25200 CLRAG_03550 1527 Aldo/ketoreductase CAETHG_0821 CUU_c28210 CLRAG_09160 1528 aromatic alcohol dehydrogenase (NADP+) CAETHG_3819 CLJU_cl7070 CLRAG_33940 1529 Aldo/ketoreductase 1.1.1.21 CAETHG_3890 CUU_cl7820 CLRAG_00890 1530 Uncharacterized YloU conserved protein of the alkaline shock protein family (Asp23) CAETHG_3200 CUU_cllllO CLRAG_12350 1531 Uncharacterized YloU conserved protein of the alkaline shock protein family (Asp23) CAETHG_3349 CUU_cl2680 CLRAG_11130 1532 D-lactate dehydrogenase 1.1.1.28 CAETHG_1147 CUU_c32190 CLRAG_02820 1533 Pimeloyl-ACP Methyl Ester Carboxylesterase CAETHG_3573, CAETHG_3862 CLJU_cl7490, CUU_cl4740 CLRAG_20450 1534 Protein of the cystathione beta-lyase family involved in aluminum resistance CAETHG_0206 CLJU_c21200 CLRAG_30780 1535 putative selenium metabolism protein SsnA CAETHG_0447 CUU_c23820 CLRAG_17350 1536 Cytosine/adenosine deaminase CAETHG_0680 CUU_c26110 CLRAG_04190 1537 Cytosine/adenosine deaminase 3.5.4.3 CAETHG_1058 CLJU_c30530 CLRAG_15950 1538 amido hydrolase CAETHG_1246 CUU_c33470 CLRAG_32300 1539 amido hydrolase 3.5.1.47 CAETHG_3847 CUU_cl7340 CLRAG_29240 1540 ComFC competence protein CAETHG_2362 CUU_c02610 CLRAG_28210 1541 L-asparagine transporter CAETHG_2486 CUU_c04180 CLRAG_26880 1542 Amino acid transporter CAETHG_1744 CUU_c38960 CLRAG_21140 1543 L-asparagine transporter CAETHG_1909 CLJU_c40660, CUU_cl6020 CLRAG_25010 1544 Efflux protein threonine/homoserine/homoserine lactone CAETHG_4019 CUU_cl8870 CLRAG_40130 1545 Putative aminopeptidase FrvX CAETHG_3608 CUU_cl5060 CLRAG_24310 1546 Aspartyl aminopeptidase CAETHG_0278 CUU_c21880 CLRAG_31420 1547 Aspartate/methionine/tyrosine aminotransferase 2.6.1.23, 2.6.1.1 CAETHG_0933 CUU_c29390 CLRAG_35390 1548 aminotransferase 2.6.1,- CAETHG_1350 CUU_c34540 CLRAG_14620 1549 taurine-2-oxoglutarate transaminase 2.6.1.62 CAETHG_1499 CUU_c35920 CLRAG_06420 1550 aspartate aminotransferase 2.6.1.51, 2.6.1.44 CAETHG_2210 CUU_c00960 CLRAG_19620 1551 aspartate aminotransferase 2.6.1.51, 2.6.1.44 CAETHG_2224 CUU_c01130 CLRAG_30270 1552 Phenylacetate coenzyme A-ligase PaaK family of proteins with adenylate-forming domain CAETHG_0467 CUU_c24010 CLRAG_17150 1553 acyl-CoA synthetase 6.2.1.3 CAETHG_1784 CLJU_c39390 CLRAG_21600 1554 anaerobic activating protein CAETHG_2288 CUU_c01850 CLRAG_27450

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ribonucleoside triphosphate reductase 1555 AB protein of the II stage of sporulation (anti-sigma F factor) CAETHG_1294 CUU_c33960 CLRAG_14110 1556 DNA binding protein type AgaC CAETHG_0064 CUU_cl9840 CLRAG_39240 1557 Arginine utilization protein RocB CAETHG_0384 CUU_c23210 CLRAG_01520 1558 arginine decarboxylase 4.1.1.18, 4.1.1.19, 4.1.1.17 CAETHG_1321 CUU_c34220 CLRAG_14370 1559 aspartate aminotransferase 2.6.1.9, 2.6.1.58, 2.6.1.1 or 2.6.1.9, 2.6.1.57, 2.6.1.23, 2.6.1.78, 2.6.1.5, 2.6.1.1 CAETHG_2537 CUU_c04650 CLRAG_38030 1560 trans-repressor of the arsenic resistance operon ArsD CAETHG_3664 CUU_cl5650 CLRAG_32710 1561 Predicted ATPase CAETHG_0931 CUU_c29370 CLRAG_33860 1562 DNA helicase-2 / ATP-dependent DNA helicase PcgA CAETHG_1692 CUU_c38340 CLRAG_20810 1563 DNA helicase-2 / ATP-dependent DNA helicase PcgA CAETHG_3749 CUU_cl6530 CLRAG_33340 1564 cell division protease FtsH CAETHG_1693 CUU_c38350 CLRAG_20820 1565 DNA and RNA helicase superfamily II CAETHG_0361 CUU_c22990 CLRAG_01790 1566 DNA and RNA helicase superfamily II CAETHG_3006 CUU_c09120 CLRAG_13900 1567 ATP-dependent RNA helicase SUPV3L1/SUV3 CAETHG_4041 CUU_cl9070 CLRAG_39950 1568 hypothetical protein CAETHG_1975 CUU_c41340 CLRAG_23530 1569 hypothetical protein CAETHG_2055 CUU_c42310 CLRAG_05420 1570 tRNA biosynthesis protein threonylcarbamoyladenosine TsaE CAETHG_1674 CUU_c38180 CLRAG_20640 1571 ATP-dependent protease C1p, ATP-binding subunit C1pC CAETHG_1974 CUU_c41330 CLRAG_23520 1572 cell division transport system, ATP-binding protein CAETHG_2422 CLJU_cO3O7O CLRAG_28680 1573 tRNA(He)-lysidine synthase TilS/MesJ CAETHG_2551 CUU_cO479O CLRAG_38170 1574 ATP-binding cassette protein uup subfamily F CAETHG_2933 CUU_c08390 CLRAG_08060 1575 magnesium chelatase family protein CAETHG_3381 CUU_cl2980 CLRAG_10810 1576 penicillin binding protein CAETHG_2700 CUU_c06020 CLRAG_07250 1577 class A beta-lactamase CAETHG_3737 CUU_cl6430 CLRAG_33230 1578 penicillin binding protein 1A CAETHG_1292 CUU_c33940 CLRAG_14090 1579 substrate-specific component of the biotin transport system CAETHG_0507 CUU_c24470 CLRAG_30100 1580 biotincarboxyl transport protein, acetylCoA carboxylase 6.3.4.14 CAETHG_2044 CUU_c42140 CLRAG_05250 1581 biotin synthase CAETHG_1691 CUU_c38330 CLRAG_20800 1582 Biotin-dependent enzyme CAETHG_0132 CUU_c20500 CLRAG_19520 1583 4-azaleucine-resistant probable AzIC transporter CAETHG_3451 CUU_cl3690 CLRAG_10180 1584 cation:H+-antiporter CAETHG_2476 CUU_c04130 CLRAG_26920 1585 cAMP-binding domain of CRP or regulatory subunit of cAMP-dependent protein kinases CAETHG_3496 CUU_cl4150 CLRAG_09470 1586 NDP sugar epimerase, including UDPGlcNAc inverting 4,6-dehydratase FlaAl and capsule polysaccharide biosynthesis protein EpsC CAETHG_1317 CUU_c34180 CLRAG_14330

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1587 Protein biosynthesis of polysaccharide capsule CAETHG_2591 CUU_c05140 CLRAG_38530 1588 protein tyrosine phosphatase CAETHG_2592 CUU_c05150 CLRAG_38540 1589 xylulokinase 2.7.1.17 CAETHG_3597 CUU_cl4910 CLRAG_20240 1590 cardiolipin synthase CAETHG_0896 CUU_c29040 CLRAG_35040 1591 cardiolipin synthase CAETHG_2984 CUU_c08890 CLRAG_07590 1592 transporter of the family of facilitated diffusion of cations proteins CAETHG_0534 CUU_c24690 CLRAG_18140 1593 glycoside/pentoside/hexuronidation simporter of the GPH family CAETHG_2234 CUU_c01250 CLRAG_30170 1594 Cd2+/Zn2+-expanding ATPase CAETHG_0899 CUU_c29070 CLRAG_35070 1595 Ca2+-transporting ATPase CAETHG_2779 CUU_c06890 CLRAG_18720 1596 P-type ATPase (transporter) superfamily HAD subfamily IC CAETHG_2880 CUU_c07870 CLRAG_25350 1597 Ca2+-transporting ATPase CAETHG_3138 CUU_cl0480 CLRAG_12890 1598 hydrophobic/amphiphilic exporter-1 HAE1 family CAETHG_0391 CUU_c23280 CLRAG_01450 1599 CDP-diacylglycerol glycerol-3-phosphate-3phosphatidyltransferase 2.7.8.5 CAETHG_1386 CUU_c34880 CLRAG_26120 1600 RodA protein, which determines the shape of the rod CAETHG_3814 CUU_cl7020 CLRAG_33900 1601 sporulation stage V protein D (sporulation specific penicillin binding protein) CAETHG_1729, CAETHG_3146 CLJU_cl0560, CUU_c38810 CLRAG_21070 1602 cell division protein FtsW, lipid Nflippase CAETHG_2429 CUU_c03140 CLRAG_28750 1603 cell division protein FtsW CAETHG_3150 CUU_cl0600 CLRAG_12740 1604 cell division protease FtsH CAETHG_2710 CUU_c06110 CLRAG_07390 1605 LYSOZYME CAETHG_1001 CUU_c30020 CLRAG_15660 1606 N-acetylmuramoyl-E-alanine amidase CAETHG_1891 CUU_c40480 CLRAG_22670 1607 Beta-N-acetylglucosaminidase CAETHG_2267 CUU_c01670 CLRAG_27270 1608 LysM domain-containing protein CAETHG_2538 CUU_c04660 CLRAG_38040 1609 N-acetylmuramoyl-E-alanine amidase CAETHG_2554 CUU_c04820 CLRAG_38200 1610 Putative cell wall binding protein containing repeat 2 CAETHG_0540 CUU_c24750 CLRAG_18070 1611 Putative cell wall binding protein containing repeat 2 CAETHG_0856 CUU_c28610 CLRAG_34690 1612 pili assembly protein Flp/PilA CAETHG_0879 CUU_c28830 CLRAG_34910 1613 Putative cell wall binding protein containing repeat 2 CAETHG_0988 CUU_c29890 CLRAG_17030 1614 Putative binding protein cell wall CAETHG_1543, CAETHG_2577 CLJU_c36350, CUU_c05000 CLRAG_38390 1615 Putative cell wall binding protein containing repeat 2 CAETHG_2557 CUU_c04840 CLRAG_38220 1616 Putative cell wall binding protein containing repeat 2 CAETHG_2588 CUU_c05110 CLRAG_38500 1617 Putative cell wall binding protein containing repeat 2 CAETHG_2589 CUU_c05120 CLRAG_38510 1618 Putative binding protein cell wall CAETHG_2655, CAETHG_3968 CLJU_cl8600, CLJU_cO563O, CUU_c32530 CLRAG_00090 1619 Putative binding protein cell wall CAETHG_2960 CUU_c08660 CLRAG_07830 1620 Putative binding protein cell wall CAETHG_3980 CUU_cl8660 CLRAG_16980 1621 cell division initiation protein CAETHG_3159 CUU_cl0690 CLRAG_12650 1622 molecular chaperone DnaJ CAETHG_2892 CUU_c07990 CLRAG_25470 1623 chemotaxis protein CheX CAETHG_4018 CUU_cl8860 CLRAG_40140

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1624 sensor kinase CheA, two-component system, chemotaxis protein family CAETHG_0310 CUU_c22120 CLRAG_31700 1625 purine binding chemotaxis protein CheW CAETHG_0309 CUU_c22110 CLRAG_31690 1626 two-component system of the chemotaxis protein family, response regulator CheY CAETHG_0311, CAETHG_3040 CUU_c22130, CUU_c09450 CLRAG_31710 1627 Methyl acceptor chemotaxis protein (MCP) containing a signaling domain CAETHG_1064 CUU_c30600 CLRAG_16010 1628 Thiamine kinase CAETHG_1812 CUU_c39660 CLRAG_21910 1629 chromate transporter CAETHG_1526 CLJU_c36160 CLRAG_24020 1630 chromate transporter CAETHG_3865 CLJU_cl7570 CLRAG_01170 1631 chromosome separation protein CAETHG_2114 CUU_c42880 CLRAG_25690 1632 chromosome separation protein of the PahrB family CAETHG_2115 CUU_c42890 CLRAG_25700 1633 2-aminoadipate transaminase CAETHG_0036, CAETHG_0213 CUU_c21270, CUU_cl9590 CLRAG_39530 1634 Substrate-specific CoA activase enzyme, putative CAETHG_0182 CUU_c20980 CLRAG_19040 1635 protein containing methylmalonyl-CoAmutase C-terminal domain/corrinoid containing proteins, methyltransferase related CAETHG_0193, CAETHG_4045 CUU_c21080, CUU_cl9110 CLRAG_30660 1636 cobalt/nickel transport system, ATP-binding protein CAETHG_0854 CUU_c28590 CLRAG_34670 1637 cobalt/nickel transport system, ATP-binding protein CAETHG_1131 CUU_c32030 CLRAG_02660 1638 transport system of the coupling factor of energy metabolism, ATP- binding protein CAETHG_1917 CUU_c40740 CLRAG_22930 1639 transport system of the coupling factor of energy metabolism, ATP- binding protein CAETHG_1918 CUU_c40750 CLRAG_22940 1640 energy metabolism coupling factor transport system, permease protein CAETHG_1916 CUU_c40730 CLRAG_22920 1641 cobalt/nickel transport system, permease protein CAETHG_1132 CUU_c32040 CLRAG_02670 1642 cobalt/nickel transport system, permease protein CAETHG_0321 CUU_c22230 CLRAG_31810 1643 cobalt/nickel transport system, permease protein CAETHG_1219 CUU_c33200 CLRAG_15060 1644 cobalt/nickel transport system, permease protein CAETHG_0855 CUU_c28600 CLRAG_34680 1645 hypothetical protein CAETHG_2719 CUU_cO619O CLRAG_07470 1646 CO-dehydrogenase maturation factor CAETHG_1612 CUU_c37590 CLRAG_37000 1647 CO-dehydrogenase maturation factor CAETHG_1619 CUU_c37660 CLRAG_37070 1648 Cold shock protein (containing a beta-ribbon motif, CspA family) CAETHG_1223 CUU_c33240 CLRAG_15020 1649 CotEC competence protein CAETHG_2749 CUU_cO659O CLRAG_18400 1650 CopG family transcription regulator/EndoAl antitoxin CAETHG_2418 CUU_c03030 CLRAG_28640 1651 protein containing a methylmalonyl-CoAmutase C-terminal domain CAETHG_0139, CAETHG_0154, CAETHG_0150 CUU_c20700, CLJU_c20670, CUU_c20560 CLRAG_30740 1652 Methanogenic corrinoid protein MtbCl CAETHG_0159 CUU_c20740 CLRAG_19260 1653 Uroporphyrinogen decarboxylase (URO-D) CAETHG_2845, CAETHG_2850 CLJU_cO757O, CUU_cO752O CLRAG_32350 1654 Protein SGSB CAETHG_0397 CUU_c23330 CLRAG_01410 1655 Protein SGSB CAETHG_0398 CUU_c23340 CLRAG_01400 1656 cAMP-binding domain of CRP or CAETHG_0443 CUU_c23780 CLRAG_17390

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regulatory subunit of cAMP-dependent protein kinases 1657 CRP/FNR family transcriptional regulator, anaerobic regulatory protein CAETHG_3172 CUU_cl0830 CLRAG_03130 1658 MFS-CP family transporter, cyanate transporter CAETHG_0544 CUU_c24790 CLRAG_18000 1659 Kynureninformamidase CAETHG_0429 CUU_c23650 CLRAG_17520 1660 Kynureninformamidase CAETHG_0484, CAETHG_2965 CUU_c08710, CUU_c24260 CLRAG_24930 1661 D-3-phosphoglycerate dehydrogenase 1.1.1.95 CAETHG_1065 CUU_c30610 CLRAG_16020 1662 O-tyrosyl-tRNA(Tyr)-deacylase CAETHG_1268 CUU_c33700 CLRAG_24580 1663 putative hydrolase of selenium metabolism CAETHG_0446 CUU_c23810 CLRAG_17360 1664 sporulation protein PdaB family polysaccharide deacetylase CAETHG_1360 CUU_c34640 CLRAG_14720 1665 EDD domain-containing protein of the DegV family CAETHG_1763 CUU_c39180 CLRAG_21330 1666 putative dehydratase family YjhG/YagF 4.2.1.9 CAETHG_2179 CUU_c00610 CLRAG_19970 1667 NAD(P)-dependent dehydrogenase of the short-chain alcohol dehydrogenase family 1.1.1.0, 2.3.1.86, 1.1.1.100, 1.1.1.1, 2.3.1.85 CAETHG_0079, CAETHG_0982 CLJU_cl9990, CUU_c29830 CLRAG_39050 1668 Predicted dehydrogenase CAETHG_0673 CLJU_c26040 CLRAG_04130 1669 NAD(P)-dependent dehydrogenase of the short-chain alcohol dehydrogenase family 2.3.1.85, 2.3.1.86, 1.1.1.1, 1.1.1.100, 1.1.1.0 CAETHG_1743 CUU_c38950 CLRAG_21130 1670 hypothetical protein CAETHG_2060 CUU_c42360 CLRAG_05470 1671 dGTPase 3.1.5.1 CAETHG_2475 CUU_c04120 CLRAG_26930 1672 TatD DNase family protein CAETHG_2276 CUU_c01740 CLRAG_27340 1673 4-hydroxytetrahydrodipicolinate synthase 4.2.1.52 CAETHG_2446 CUU_c03840 CLRAG_28910 1674 Predicted Fe-Mo cluster-binding protein of the NifX family CAETHG_1623 CUU_c37690 CLRAG_37110 1675 transporter of the family of facilitated diffusion of cations proteins CAETHG_1456 CUU_c35480 CLRAG_06010 1676 NRAMP (natural resistance associated macrophage protein), metal ion transporters CAETHG_2064 CUU_c42390 CLRAG_05530 1677 CBS domain-containing protein CAETHG_3696 CUU_cl5990 CLRAG_32980 1678 NRAMP (natural resistance associated macrophage protein), metal ion transporters CAETHG_3697 CUU_cl6000 CLRAG_32990 1679 Uncharacterized conserved YlxW protein of the UPF0749 family CAETHG_3152 CUU_cl0620 CLRAG_12720 1680 Uncharacterized conserved YlxW protein of the UPF0749 family CAETHG_3154 CUU_clO64O CLRAG_12700 1681 replicative DNA helicase CAETHG_2096 CUU_c42710 CLRAG_25520 1682 protein containing a prepilin-type N-terminal hydrolysis/methylation domain CAETHG_3183 CUU_cl0940 CLRAG_12520 1683 MutS domain III CAETHG_0272 CUU_c21820 CLRAG_31360 1684 MutS domain V CAETHG_0316 CUU_c22180 CLRAG_31760 1685 adenine-specific DNA methyltransferase CAETHG_1296 CUU_c33980 CLRAG_14130 1686 DNA replication protein DnaC CAETHG_2054 CUU_c42230 CLRAG_05340 1687 protein containing DnaD- and phage-associated domain CAETHG_2053 CUU_c42220 CLRAG_05330 1688 competence protein CotEA CAETHG_2837 CUU_c07450 CLRAG_32240 1689 putative protein DNA modification/repair containing CAETHG_1034 CUU_c30270 CLRAG_15910

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SAM radical 1690 Predicted DNA-binding protein of the UPF0251 family CAETHG_1624 CUU_c37700 CLRAG_37120 1691 putative transcriptional regulator CAETHG_1667 CUU_c32500 CLRAG_36110 1692 diadenylate cyclase CAETHG_1972 CUU_c41310 CLRAG_23500 1693 electron transport complex type RnfABCDGE, subunit B 1.18.1.3 CAETHG_3232 CUU_cll410 CLRAG_12040 1694 electron transport complex protein RnfC 1.18.1.3 CAETHG_3227 CLJU_cll360 CLRAG_12090 1695 electron transport complex protein RnfG 1.18.1.3 CAETHG_3229 CLJU_cll380 CLRAG_12070 1696 protein containing a small GTP-binding domain CAETHG_0529 CUU_c24640 CLRAG_18260 1697 Endodeoxyribonuclease RusA CAETHG_1596 CUU_c37440 CLRAG_36850 1698 hypothetical protein CAETHG_2823 CUU_cO731O CLRAG_26530 1699 PhzF family phenazine biosynthesis protein CAETHG_0019 CUU_cl9420 CLRAG_39690 1700 PhzF family phenazine biosynthesis protein CAETHG_3885 CUU_cl7770 CLRAG_00940 1701 erythromycin esterase CAETHG_0637 CUU_c25680 CLRAG_03880 1702 ΝΤΕ family protein CAETHG_0169 CUU_c20840 CLRAG_19160 1703 hypothetical protein CAETHG_1027 CUU_c30200 CLRAG_15800 1704 ethanolamine utilization protein EutJ CAETHG_1826, CAETHG_3282 CUU_c39800, CUU_cll910 CLRAG_22050 1705 ethanolamine utilization protein EutQ CAETHG_1821, CAETHG_3285 CLJU_c39750, CUU_cll940 CLRAG_22000 1706 ABC exinuclease, subunit A CAETHG_3574 CUU_cl4750 CLRAG_20400 1707 DNA polymerase-3, epsilon subunit CAETHG_4048 CUU_cl9140 CLRAG_39940 1708 DNA polymerase-3, epsilon subunit CAETHG_1533 CUU_c36230 CLRAG_23950 1709 Exopolysaccharide biosynthesis protein CAETHG_0968 CUU_c29700, CUU_cl5840 CLRAG_35700 1710 family of exopolysaccharides capsules CAETHG_2593 CUU_cO516O CLRAG_38550 1711 Exopolysaccharide biosynthesis protein CAETHG_2955 CUU_c08610 CLRAG_07880 1712 hypothetical protein CAETHG_1888 CUU_c40450 CLRAG_22640 1713 Dehydrogenase (flavoprotein) CAETHG_0813 CUU_c27270 CLRAG_08970 1714 NADPH-dependent 2,4-dienoyl-CoA reductase, sulfur reductase CAETHG_0943 CUU_c29490 CLRAG_35480 1715 glycolate oxidase 1.1.3.15 CAETHG_0117, CAETHG_2688, CAETHG_0382 CIJU_c05910, CUU_c23190, CUU_c20350 CLRAG_25940 1716 glycolate oxidase 1.1.3.15 CAETHG_0244 CUU_c21570 CLRAG_31160 1717 glycolate oxidase 1.1.3.15 CAETHG_3473 CLJU_cl3900 CLRAG_09940 1718 Succinyl-CoA synthetase, alpha subunit CAETHG_0431 CUU_c23670 CLRAG_17500 1719 hypothetical protein CAETHG_3907 CUU_cl7980 CLRAG_00650 1720 Enzyme YgiQ of the superfamily of proteins containing the SAM radical, family UPF0313 CAETHG_0298 CUU_c22000 CLRAG_31530 1721 Enzyme of the superfamily of proteins containing the SAM radical, MoaA/NifB/PqqE/SkfB family CAETHG_0786, CAETHG_2300 CLJU_c27030, CUU_cO197O CLRAG_09540 1722 uncharacterized protein CAETHG_1274 CUU_c33760 CLRAG_24520 1723 hypothetical protein CAETHG_2018 CUU_c41890 CLRAG_05000 1724 uncharacterized protein of the family of proteins containing the SAM radical CAETHG_2825 CUU_cO733O CLRAG_26510 1725 electron transport protein HydN 1.12.1.4, 1.1.99.33 CAETHG_2799 CUU_cO7O8O CLRAG_18930 1726 Protein regulating Fe2+ or Zn2+ uptake CAETHG_2706 CUU_cO6O7O CLRAG_07340 1727 iron complex transport system, ATP-binding protein CAETHG_2679 CUU_cO584O CLRAG_07080 1728 iron complex transport system, substrate-binding protein CAETHG_2677 CUU_cO582O CLRAG_07060

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1729 iron complex transport system, permease protein CAETHG_2678 CUU_c05830 CLRAG_07070 1730 An uncharacterized protein containing 2Fe-2 and 4Fe-45 clusters and a DUF4445 domain CAETHG_1606 CUU_c37530 CLRAG_36940 1731 bacterioferritin CAETHG_0047 CUU_cl9700 CLRAG_39440 1732 ferrous iron transporter protein B CAETHG_0253 CUU_c21660 CLRAG_31250 1733 ferrous iron transport protein A CAETHG_0252 CUU_c21650 CLRAG_31240 1734 flagellum protein FliO/FliZ CAETHG_3123 CUU_cl0330 CLRAG_13040 1735 flagellar operon protein CAETHG_3119 CUU_cl0290 CLRAG_13080 1736 protein FlgD modification of flagellar kinetosome rod CAETHG_3118 CUU_cl0280 CLRAG_13090 1737 flagellar hook protein FlgE CAETHG_3120 CUU_cl0300 CLRAG_13070 1738 flagellar hook length control protein FliK CAETHG_3117 CUU_cl0270 CLRAG_13100 1739 chemotaxis protein MotB CAETHG_2252 CUU_c01460 CLRAG_27120 1740 Flagellar motor switch protein FliN/FliY CAETHG_3043 CUU_c09480 CLRAG_13620 1741 c-di-GMP-binding flagellar inhibition protein YcgR containing PilZNR and PilZ domains CAETHG_3130 CLJU_cl0400 CLRAG_12970 1742 flagellum protein FlbD CAETHG_3121 CUU_cl0310 CLRAG_13060 1743 flagellar biosynthesis protein FlhG CAETHG_3129 CLJU_clO39O CLRAG_12980 1744 NADH-FMN oxidoreductase RutF of the flavin reductase family (DIM6/NTAB) CAETHG_0025 CUU_cl9480 CLRAG_39630 1745 NADH-FMN oxidoreductase RutF of the flavin reductase family (DIM6/NTAB) CAETHG_1451 CUU_c35430 CLRAG_05970 1746 Flavodoxin CAETHG_0034 CUU_cl9570 CLRAG_39560 1747 Multimeric flavodoxin WrbA CAETHG_0543 CUU_c24780 CLRAG_18010 1748 Flavodoxin domain-containing protein CAETHG_1387 CUU_c34890 CLRAG_26130 1749 Flavodoxin CAETHG_3868 CUU_cl7600 CLRAG_01140 1750 flavodoxin, short chain CAETHG_3483 CLJU_cl4000 CLRAG_09330 1751 hypothetical protein CAETHG_0220 CUU_c21340 CLRAG_30900 1752 Flavorubredoxin CAETHG_0291 CUU_c21940 CLRAG_31490 1753 hypothetical protein CAETHG_2057 CUU_c42330 CLRAG_05440 1754 FMN-dependent dehydrogenase, including L-lactate dehydrogenase and isopentenyl diphosphate isomerase type II CAETHG_1336 CUU_c34360 CLRAG_14440 1755 peptidylprolyl cis-trans isomerase C CAETHG_2226 CUU_c01180 CLRAG_30240 1756 formate dehydrogenase, large subunit 1.2.1.43 CAETHG_0084 CUU_c20040 CLRAG_29330 1757 FdhD protein 1.1.99.33 CAETHG_2793 CLJU_cO7O2O CLRAG_18870 1758 Fur family transcriptional regulator, peroxide stress response regulator CAETHG_1463 CUU_c35550 CLRAG_06080 1759 type IV pili assembly protein PilB CAETHG_3179 CLJU_clO9OO CLRAG_12560 1760 diguanylate cyclase domain-containing protein (GGDEF) CAETHG_0826 CUU_c28290 CLRAG_34370 1761 diguanylate cyclase domain-containing protein (GGDEF) CAETHG_1731 CUU_c38830 CLRAG_21090 1762 mannose-1-phosphate guanylyltransferase CAETHG_0735 CUU_c26540 CLRAG_08420 1763 putative glutamine amidotransferase CAETHG_1555 CUU_c36940 CLRAG_36470 1764 putative glutamine amidotransferase CAETHG_1911 CUU_c40680 CLRAG_22870 1765 uncharacterized protein CAETHG_0070 CLJU_cl9900 CLRAG_39180 1766 Glycine cleavage system H protein 1.8.1.4, 2.1.2.10 CAETHG_0475, CAETHG_1607 CLJU_c37540, CUU_c24170 CLRAG_24840 1767 UDP: flavonoid glycosyltransferase YjiC YdhE family CAETHG_3490 CUU_cl4090 CLRAG_09440 1768 Predicted glycosyl hydrolase of the GH43/DUF377 family CAETHG_2683 CUU_c05880 CLRAG_07120

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1769 1,2-diacylglycerol-3-alpha-glucose-alpha- 1,2-galactosyltransferase CAETHG_0044 CUU_cl9670 CLRAG_39470 1770 hypothetical protein CAETHG_0223, CAETHG_3310 CLJU_cl2280, CUU_c21370 CLRAG_30930 1771 Glycosyltransferase involved in cell wall bisynthesis CAETHG_0736 CUU_c26550 CLRAG_08430 1772 UDP: flavonoid glycosyltransferase YjiC YdhE family CAETHG_0924 CUU_c29310 CLRAG_35320 1773 Family 2 glycosyltransferase CAETHG_1251 CUU_c33520 CLRAG_24760 1774 Glycosyltransferase involved in cell wall bisynthesis 2.4.1.52 CAETHG_1303 CLJU_c34050 CLRAG_14200 1775 Glycosyltransferase, catalytic subunit of cellulose synthase and poly-beta1, b-N-acetylglucosamine synthase CAETHG_1313 CUU_c34150 CLRAG_14300 1776 Glycosyltransferase involved in cell wall bisynthesis CAETHG_1314 CUU_c34160 CLRAG_14310 1777 Glycosyltransferase involved in cell wall bisynthesis CAETHG_1315 CUU_c34170 CLRAG_14320 1778 dolichol phosphate mannosyltransferase CAETHG_1737, CAETHG_2517 CLJU_c38890, CLJU_c04450 CLRAG_37810 1779 Glycosyltransferase involved in cell wall bisynthesis CAETHG_2302 CUU_c01990 CLRAG_27590 1780 Glycosyltransferase involved in cell wall bisynthesis CAETHG_2309 CLJU_c02040 CLRAG_27640 1781 Dolichyl phosphate mannose protein mannosyltransferase CAETHG_2519 CLJU_c04470 CLRAG_37830 1782 Glycosyltransferase involved in cell wall bisynthesis CAETHG_2527 CUU_c04550 CLRAG_37910 1783 polyprenylglycosylphosphotransferase biosynthesis of exopolysaccharides CAETHG_2598, CAETHG_2622 CLJU_c05410, CUU_c05210 CLRAG_38600 1784 rhamnosyltransferase CAETHG_2623 CUU_c05420 CLRAG_38880 1785 Group 1 glycosyltransferases CAETHG_2625 CLJU_c05430 CLRAG_38890 1786 4-amino-4-deoxy-E-arabinose transferase CAETHG_3709 CUU_cl6140 CLRAG_33110 1787 Catechol 2,3-dioxygenase CAETHG_0065 CUU_cl9850 CLRAG_39230 1788 DNA-binding transcriptional regulator of the GntR family CAETHG_0068 CUU_cl9880 CLRAG_39200 1789 putative GTP pyrophosphokinase 2.7.6.5 CAETHG_2376 CLJU_c02740 CLRAG_28340 1790 GTP-binding protein HfIX CAETHG_1289 CLJU_c33910 CLRAG_14060 1791 GTP binding protein CAETHG_1469 CUU_c35610 CLRAG_06140 1792 hypothetical protein CAETHG_3142 CUU_cl0520 CLRAG_12820 1793 GTP binding protein CAETHG_3329 CUU_cl2470 CLRAG_11330 1794 GTPase A of ribosome biogenesis CAETHG_3377 CLJU_cl2950 CLRAG_10850 1795 GTP binding protein LepA CAETHG_2887 CLJU_c07940 CLRAG_25420 1796 GTPase of ribosome biogenesis CAETHG_3345 CUU_cl2630 CLRAG_11170 1797 HDIG domain-containing protein CAETHG_1638 CLJU_c38120 CLRAG_37500 1798 HD domain containing protein CAETHG_2215 CLJU_c01040 CLRAG_30360 1799 class II c-di-GMP phosphodiesterase (or its inactivated variant), HD-GYP domain CAETHG_2708 CUU_c06090 CLRAG_07370 1800 3'-5'-exoribonuclease CAETHG_1750 CLJU_c39020 CLRAG_21200 1801 molecular chaperone GrpE CAETHG_2890 CLJU_cO797O CLRAG_25450 1802 ACR3 family arsenite transporter CAETHG_3666 CUU_cl5670 CLRAG_32730 1803 copper ion binding protein CAETHG_0556 CUU_c24890 CLRAG_17890 1804 DNA helicase-2 / ATP-dependent DNA helicase PcgA CAETHG_0292 CUU_c21950 CLRAG_31500 1805 DNA helicase-2 / ATP-dependent DNA helicase PcgA CAETHG_0838 CUU_c28400 CLRAG_34480 1806 DNA or RNA helicase superfamily II, CAETHG_3565 CUU_cl4660 CLRAG_20540

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SNF2 family 1807 Predicted protein binding heme/steroids CAETHG_0859 CUU_c28640 CLRAG_34720 1808 histidine triad (HIT) family protein 3.6.1.17 CAETHG_2897 CUU_c08030 CLRAG_08330 1809 putative Holliday structure resolvase 4.1.2.4 CAETHG_3299 CUU_cl2170 CLRAG_11630 1810 hydroxylamine reductase 1.7.99.1 CAETHG_0812 CUU_c27260 CLRAG_08960 1811 YaaH spore germination protein CAETHG_0066, CAETHG_3996 CLJU_cl8760, CUU_cl9860 CLRAG_39220 1812 Predicted amidohydrolase CAETHG_0225 CUU_c21390 CLRAG_30950 1813 hypothetical protein CAETHG_0559 CUU_c24920 CLRAG_17860 1814 L-ascorbate metabolism protein UlaG of the beta-lactamase superfamily CAETHG_0696 CUU_c26200 CLRAG_04280 1815 ADP-ribose pyrophosphatase 3.6.1.13 CAETHG_1133 CUU_c32050 CLRAG_02680 1816 Metal-dependent hydrolase of superfamily II beta-lactamases CAETHG_1283 CUU_c33850 CLRAG_24430 1817 hypothetical protein CAETHG_1684 CUU_c38270 CLRAG_20740 1818 variant 3 of the subfamily IA haloacid dehalogenase superfamily, containing DD or ED in the third motif/variant 1 of the subfamily IA haloacid dehalogenase superfamily, containing Dx(3-4)D or Dx(3-4)E in the third motif CAETHG_2015 CUU_c41860 CLRAG_04970 1819 hypothetical protein CAETHG_2183 CUU_c00650 CLRAG_19930 1820 endoglucanase CAETHG_2220 CLJU_c01090 CLRAG_30310 1821 endoglucanase CAETHG_2221 CUU_c01100 CLRAG_30300 1822 endoglucanase CAETHG_2222 CUU_c01110 CLRAG_30290 1823 L-ascorbate metabolism protein UlaG of the beta-lactamase superfamily CAETHG_2290 CUU_c01870 CLRAG_27470 1824 Glyoxylase superfamily II beta-lactamase CAETHG_2656 CUU_c05640 CLRAG_06860 1825 putative NAD metabolic hydrolase of the HD superfamily CAETHG_2833 CUU_c07410 CLRAG_26430 1826 hydrolase CAETHG_2946 CUU_c08520 CLRAG_07970 1827 hypothetical protein CAETHG_3237 CUU_cll460 CLRAG_11990 1828 hypothetical protein CAETHG_3242 CUU_cll510 CLRAG_11940 1829 8-oxo-dGTP pyrophosphatase MutT of the NUDIX family CAETHG_3426 CUU_cl3420 CLRAG_10370 1830 putative HAD superfamily hydrolase CAETHG_3815 CUU_cl7030 CLRAG_33910 1831 hypothetical protein CAETHG_3889 CUU_cl7810 CLRAG_00900 1832 L isophospholipase L1 CAETHG_3944 CUU_cl8370 CLRAG_00300 1833 hydroxylamine reductase 1.7.99.1 CAETHG_2866 CLJU_cO773O CLRAG_25270 1834 Drug/metabolite transporter (DMT) superfamily permease CAETHG_3966 CUU_cl8590 CLRAG_00110 1835 Phage integrase family protein CAETHG_0785 CLJU_c27020 CLRAG_09550 1836 integrase/recombinase XerD CAETHG_3217 CUU_cll260 CLRAG_12190 1837 DJ-1/Pfpl family protein CAETHG_3867 CUU_cl7590 CLRAG_01150 1838 voltage-gated potassium channel CAETHG_2684 CUU_c05890 CLRAG_07130 1839 Large subunit of hydrogenase containing an iron atom, C-terminal domain CAETHG_0110 CLJU_c20290 CLRAG_26000 1840 Alcohol dehydrogenase class IV 1.1.1.1, 1.1.1.72, 1.1.1.21, 1.1.1.2 CAETHG_2445 CUU_c03830 CLRAG_28900 1841 protein containing a domain with a 4Fe4S dicluster CAETHG_4056 CUU_cl9210 CLRAG_39860

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1842 Multimeric flavodoxin WrbA CAETHG_1082 CUU_c30780 CLRAG_16220 1843 NADPH-dependent FMN reductase CAETHG_3699 CUU_cl6050 CLRAG_33020 1844 2-dehydro-3-deoxyphosphogluconate aldolase / (45)-4-hydroxy-2-oxoglutarate aldolase 4.1.2.14, 4.1.3.16, 4.1.1.3 CAETHG_3443 CUU_cl3610 CLRAG_10260 1845 lipid kinase of the YegS/Rv2252/BmrU family CAETHG_2409 CUU_c02940 CLRAG_28540 1846 hypothetical protein CAETHG_3350 CUU_cl2690 CLRAG_11120 1847 lactate permease CAETHG_0248 CUU_c21610 CLRAG_31200 1848 muramoyltetrapeptide carboxypeptidase CAETHG_2241 CUU_cO135O CLRAG_27010 1849 acetylesterase CAETHG_1256 CUU_c33570 CLRAG_24710 1850 hypothetical protein CAETHG_3912 CUU_cl8030 CLRAG_00610 1851 lipoate protein ligase A 2.7.7.63 CAETHG_3015 CUU_c09210 CLRAG_13820 1852 lipoate protein ligase A 2.7.7.63 CAETHG_1221 CUU_c33220 CLRAG_15040 1853 UDP-4-amino-4,6-dideoxy-N-acetyl-beta-Ealtrosamine transaminase CAETHG_2631 CUU_c05490 CLRAG_38950 1854 Protein LysE/ArgO of the Llysine exporter family CAETHG_1838 CUU_c39920 CLRAG_22170 1855 L isophospholipase L1 CAETHG_2947 CLJU_cO853O CLRAG_07960 1856 regulatory protein containing a helix-loop-helix domain of the lysR family CAETHG_1047 CUU_c30420 CLRAG_15930 1857 DNA-binding transcriptional regulator of the LysR family CAETHG_1210 CUU_c33120 CLRAG_15200 1858 DNA-binding transcriptional regulator of the LysR family CAETHG_2037 CUU_c42070, CUU_c27740 CLRAG_05180 1859 DNA-binding transcriptional regulator of the LysR family CAETHG_2069, CAETHG_3880 CUU_c42440, CUU_cl7720 CLRAG_01010 1860 DNA-binding transcriptional regulator of the LysR family CAETHG_2089 CUU_c42630 CLRAG_05650 1861 DNA-binding transcriptional regulator of the LysR family CAETHG_3864 CUU_cl7560 CLRAG_01180 1862 soluble lytic murein transglycosylase CAETHG_1257 CUU_c33590 CLRAG_24690 1863 septum formation protein CAETHG_2812 CUU_c07200 CLRAG_26640 1864 magnesium transporter CAETHG_0285 CUU_c21890 CLRAG_31430 1865 PRC-barrel domain-containing protein CAETHG_2412 CUU_c02970 CLRAG_28580 1866 o-succinylbenzoate synthase CAETHG_3735 CUU_cl6410 CLRAG_33210 1867 manganese transport protein CAETHG_1334, CAETHG_1492 CLJU_c34340, CUU_c35850 CLRAG_06350 1868 DNA-binding transcriptional regulator of the MarR family CAETHG_0393 CUU_c23290 CLRAG_01440 1869 DNA-binding transcriptional regulator of the MarR family CAETHG_0620 CUU_c25510 CLRAG_03720 1870 DNA-binding transcriptional regulator of the MarR family CAETHG_1748 CUU_c39000 CLRAG_21180 1871 MarR family protein CAETHG_2504 CUU_c04360 CLRAG_37690 1872 DNA-binding transcriptional regulator of the MarR family CAETHG_3572, CAETHG_3861 CUU_cl7480, CUU_cl4730 CLRAG_20460 1873 MarR family transcriptional regulator, repressor of the 2-MHQ and catechol resistance regulon CAETHG_3643 CUU_cl5420 CLRAG_24050 1874 small mechanosensitive channel conductivity CAETHG_2107 CUU_c42810 CLRAG_25620 1875 GTP binding protein CAETHG_3304 CUU_cl2220 CLRAG_11580 1876 Membrane protein insertase family YidC/Oxal CAETHG_2120 CUU_c42940 CLRAG_25750 1877 Protein containing a 4Pe-45-binding domain CAETHG_3860 CUU_cl7470 CLRAG_01230

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1878 thiamine biosynthesis lipoprotein CAETHG_2065 CUU_c42400 CLRAG_05540 1879 sigma E protease regulator CAETHG_3392 CUU_cl3090 CLRAG_10700 1880 hypothetical protein CAETHG_2902 CUU_c08070 CLRAG_08280 1881 rhomboid protease GluP CAETHG_2709 CUU_c06100 CLRAG_07380 1882 Uncharacterized membrane protein YvbJ CAETHG_3093 CUU_cl0020 CLRAG_13340 1883 secretion protein of the HlyD family CAETHG_3917 CUU_cl8080 CLRAG_00570 1884 luxR family regulatory protein CAETHG_3859 CUU_cl7460 CLRAG_01240 1885 hypothetical protein CAETHG_0485 CUU_c24270 CLRAG_24940 1886 putative LexA-binding hydrolase associated with the inner membrane CAETHG_0352 CUU_c22900 CLRAG_01890 1887 Protein of the transglutaminase-like protein family CAETHG_1447 CUU_c35390 CLRAG_05930 1888 diguanylate cyclase domain-containing protein (GGDEF) CAETHG_1514 CUU_c36050 CLRAG_06540 1889 zinc transport system, ATP-binding protein CAETHG_1108 CUU_c31790 CLRAG_02420 1890 zinc transport system, permease protein CAETHG_1109 CUU_c31800 CLRAG_02430 1891 Phosphoribosyl-1,2-cyclophosphodiesterase CAETHG_2028 CUU_c41990 CLRAG_05100 1892 CTP: molybdopterin cytidylyl transferase MocA CAETHG_0465 CUU_c23990 CLRAG_17170 1893 HDIG domain-containing protein CAETHG_1673 CLJU_c38170 CLRAG_20630 1894 HDIG domain-containing protein 3.1.3.1 CAETHG_2731 CUU_c06360 CLRAG_30470 1895 D-methionine transport system, substrate binding protein CAETHG_1138 CUU_c32100 CLRAG_02730 1896 D-methionine transport system, permease protein CAETHG_2533 CUU_c04610 CLRAG_37970 1897 ABC-type Zn uptake system ZnuABC, Zn-binding component ZnuA CAETHG_1672 CUU_c38160 CLRAG_20620 1898 zinc transport system, substrate binding protein CAETHG_0318 CUU_c37880, CUU_c22200 CLRAG_31780 1899 An uncharacterized protein containing 2Fe-2 and 4Ee-45 clusters and a DUF4445 domain CAETHG_2846 CUU_c07530 CLRAG_32340 1900 7,8-dihydropterin-6-ylmethyl-4-(beta-Oribofuranosyl)-aminobenzene-5'phosphate synthase CAETHG_1393 CUU_c34950 CLRAG_26190 1901 ribonuclease J CAETHG_3302 CUU_cl2200 CLRAG_11600 1902 hypothetical protein CAETHG_0277 CUU_c21870 CLRAG_31410 1903 Beta-lactamase fold-containing RNA processing exonuclease of the Cft2 family CAETHG_1143 CUU_c32150 CLRAG_02780 1904 Rubrerythrin CAETHG_0302 CUU_c22040 CLRAG_02720 1905 methyl acceptor chemotaxis protein CAETHG_0353, CAETHG_1531 CUU_c22910, CUU_c36200 CLRAG_01880 1906 Protein containing a ligand-binding sensor domain CAETHG_0920, CAETHG_2802 CUU_c29270, CUU_c07110 CLRAG_35280 1907 methyl acceptor chemotaxis protein CAETHG_1062 CUU_c30560 CLRAG_15980 1908 methyl acceptor chemotaxis protein CAETHG_1248 CUU_c33490 CLRAG_24790 1909 methyl acceptor chemotaxis protein CAETHG_2454, CAETHG_3581 CUU_cl4810, CUU_cO392O CLRAG_29030 1910 methyl acceptor chemotaxis protein CAETHG_2457 CUU_c03950 CLRAG_29060 1911 methyl acceptor chemotaxis protein CAETHG_2549 CUU_c04770 CLRAG_38150 1912 methyl acceptor sensor chemotaxis transducer with Cache sensor CAETHG_2701 CUU_c06030 CLRAG_07260 1913 Methyl-acceptor chemotaxis protein (MCP) containing a signaling domain CAETHG_0750 CUU_c26690 CLRAG_08560 1914 Methyl-acceptor chemotaxis protein (MCP) containing a signaling domain CAETHG_2090 CUU_c42640 CLRAG_05660

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1915 methyl acceptor chemotaxis protein CAETHG_2990 CUU_cO896O CLRAG_07540 1916 methyl acceptor chemotaxis protein CAETHG_0493 CUU_c24340 CLRAG_25020 1917 Methyl-acceptor chemotaxis protein (MCP) containing a signaling domain CAETHG_0504, CAETHG_3957 CUU_c37140, CLJU_cl8500, CUU_c24440 CLRAG_30130 1918 Methyl-acceptor chemotaxis protein (MCP) containing a signaling domain CAETHG_1569, CAETHG_2487 CUU_cO419O CLRAG_26870 1919 methyl acceptor chemotaxis protein CAETHG_3469 CUU_cl3860 CLRAG_09980 1920 Protein containing a methyltransferase domain CAETHG_0515 CUU_c24540 CLRAG_23640 1921 Protein containing a methyltransferase domain CAETHG_0523 CUU_c24600 CLRAG_18280 1922 C-methylase for ubiquinone/menaquinone biosynthesis UbiE CAETHG_0593 CUU_c25250 CLRAG_03600 1923 tRNA1(\/a1)A37-N6-methylase TrmN6 CAETHG_2253 CUU_c01470 CLRAG_27130 1924 putative N6-adenine-specific DNA methylase CAETHG_2469 CUU_cO4O6O CLRAG_29170 1925 N-6-DNA methylase CAETHG_2939 CUU_cO846O CLRAG_08000 1926 [methyl-Co(1P)-methanol-specific corrinoid-containing protein]: coenzyme Mmethyltransferase CAETHG_0191, CAETHG_4046 CLJU_c21060, CUU_cl9120 CLRAG_30640 1927 EmrB/QacA subfamily drug resistance transporter CAETHG_0743 CUU_c26620 CLRAG_08490 1928 EmrB/QacA subfamily drug resistance transporter CAETHG_0939 CUU_c29450 CLRAG_35440 1929 Transmembrane secretion effector CAETHG_1057, CAETHG_2366 CLJU_cO265O, CUU_c30520 CLRAG_15940 1930 Protein of the superfamily of major transporters involved in facilitated diffusion CAETHG_1080 CUU_c30760 CLRAG_16200 1931 Sugar phosphate permease CAETHG_3444 CUU_cl3620 CLRAG_10250 1932 TatD DNase family protein CAETHG_2972 CUU_cO878O CLRAG_07710 1933 magnesium transporter CAETHG_2242 CUU_c01360 CLRAG_27020 1934 microcompartment protein PduB CAETHG_0341, CAETHG_3278 CUU_c22790, CUU_cll870 CLRAG_02000 1935 BMC domain-containing protein CAETHG_1816, CAETHG_3290 CUU_c39700, CUU_cll990 CLRAG_21950 1936 BMC domain-containing protein CAETHG_1817, CAETHG_3289 CUU_c39710, CUU_cll980 CLRAG_21960 1937 ethanolamine utilization protein EutS CAETHG_3901 CUU_cl7930 CLRAG_00700 1938 BMC domain-containing protein CAETHG_1820, CAETHG_3286 CUU_c39740, CUU_cll950 CLRAG_21990 1939 Microcompartment protein of carboxysome shell and ethanolamine utilization CcmL/EutN CAETHG_1822 CUU_c39760 CLRAG_22010 1940 BMC domain-containing protein CAETHG_1825, CAETHG_3283 CLJU_c39790, CUU_cll920 CLRAG_22040 1941 BMC domain-containing protein CAETHG_1831 CUU_c39850 CLRAG_22100 1942 BMC domain-containing protein CAETHG_1832 CUU_c39860 CLRAG_22110 1943 ethanolamine utilization protein EutN CAETHG_2801 CUU_cO71OO CLRAG_18950 1944 release factor glutamine methyltransferase CAETHG_2330 CUU_cO225O CLRAG_27850 1945 molecular chaperone DnaK CAETHG_2891 CUU_cO798O CLRAG_25460 1946 molybdate transport system, ATP-binding protein CAETHG_0313 CUU_c22150 CLRAG_31730 1947 molybdate transport system, permease protein CAETHG_0314 CUU_c22160 CLRAG_31740 1948 molybdate transport system, substrate-binding protein CAETHG_0315 CUU_c22170 CLRAG_31750 1949 putative protein biosynthesis CAETHG_2566 CUU_cO489O CLRAG_38280

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molybdopterin 1950 putative protein biosynthesis molybdopterin CAETHG_3823 CUU_cl7110 CLRAG_33980 1951 cyclic synthase pyranopterin monophosphate, MoaA subunit CAETHG_1238 CUU_c33380 CLRAG_14870 1952 cyclic synthase pyranopterin monophosphate CAETHG_0573 CUU_c25050 CLRAG_17730 1953 auxiliary factor xanthine dehydrogenase CAETHG_0466 CLJU_c24070, CUU_c24000 CLRAG_17160 1954 protein containing molybdenum pterin binding domain CAETHG_0312 CUU_c22140 CLRAG_31720 1955 protein containing molybdenum cofactor synthesis domain CAETHG_3904 CUU_cl7950 CLRAG_00680 1956 Anaerobic selenocysteine-containing dehydrogenase CAETHG_3653 CUU_cl5540 CLRAG_32620 1957 Protein containing the molybdate transport repressor domain ModE CAETHG_0458 CUU_c23920 CLRAG_17240 1958 TRNA-A37- threonylcarbamoyladenosine dehydratase CAETHG_0226 CUU_c21400 CLRAG_30960 1959 Subfamily B protein of proteins containing an ATP-binding cassette CAETHG_2986 CUU_cO891O CLRAG_07570 1960 Subfamily B protein of proteins containing an ATP-binding cassette CAETHG_2987 CUU_c08920 CLRAG_07560 1961 Membrane carboxypeptidase (penicillin binding protein) CAETHG_3692 CUU_cl5910 CLRAG_32960 1962 N-acetylmuramoyl-E-alanine amidase CAETHG_2291 CUU_c01880 CLRAG_27480 1963 sodium transport system, ATP-binding protein CAETHG_3610 CUU_cl5080 CLRAG_24290 1964 sodium transport system, permease protein CAETHG_3609 CUU_cl5070 CLRAG_24300 1965 putative MATE family efflux protein CAETHG_1861 CUU_c40120 CLRAG_22350 1966 putative MATE family efflux protein CAETHG_2938 CUU_c08450 CLRAG_08010 1967 putative MATE family efflux protein CAETHG_3500, CAETHG_3720 CUU_cl4190, CUU_cl6260 CLRAG_09520 1968 putative MATE family efflux protein CAETHG_3625 CUU_cl5230 CLRAG_24120 1969 symporter of Na+/H+-dicarboxylates CAETHG_2499 CUU_c04310 CLRAG_26750 1970 solute symporter:Na+ SSS family CAETHG_0135 CUU_c20530 CLRAG_19470 1971 hypothetical protein CAETHG_0410 CUU_c23460 CLRAG_17650 1972 nitroreductase CAETHG_0080 CUU_c20000 CLRAG_39010 1973 nitroreductase CAETHG_3639 CUU_cl5370 CLRAG_24090 1974 2,4-dienoyl-CoA reductase CAETHG_0482 CUU_c24240 CLRAG_24910 1975 2,4-dienoyl-CoA reductase CAETHG_0205 CUU_c21190 CLRAG_30770 1976 2,4-dienoyl-CoA reductase CAETHG_3603 CUU_cl4990 CLRAG_24360 1977 hypothetical protein , 1.1.1.2, 1.1.1.1, 1.1.1.72, 1.1.1.21, 1.1.1.4 CAETHG_0555, CAETHG_3954, CAETHG_1841 CUU_c39950, CUU_cl8470, CUU_c24880 CLRAG_17900 1978 NADPH-dependent FMN reductase CAETHG_0716 CUU_c26350 CLRAG_04440 1979 binuclear metal center protein of the Ybgl/SA1388 family CAETHG_2920 CUU_c08250 CLRAG_08140 1980 hydrogenase maturation protease CAETHG_0860 CUU_c28650 CLRAG_34730 1981 Transport system ABC-type nitrate/sulfonate/bicarbonate, substrate binding protein CAETHG_2975 CUU_c08800 CLRAG_07690 1982 nitroreductase CAETHG_1409 CUU_c35000 CLRAG_26270

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1983 nitroreductase CAETHG_1432 CUU_c35240 CLRAG_05750 1984 nitroreductase CAETHG_1532 CUU_c36210 CLRAG_23980 1985 nitroreductase CAETHG_3909 CUU_cl8000 CLRAG_00630 1986 exonuclease SbcC CAETHG_0113 CUU_c20320 CLRAG_25970 1987 hypothetical protein CAETHG_0426 CUU_c23620 CLRAG_17550 1988 hypothetical protein CAETHG_2780 CUU_c06900 CLRAG_18730 1989 putative vector Hydroxymethylpyrimidine CytX CAETHG_4057 CUU_cl9220 CLRAG_39850 1990 Nucleoside diphosphate sugar epimerase 5.1.3.7, 5.1.3.2 CAETHG_3091 CUU_cl0000 CLRAG_13350 1991 Chromosome separating ATPase, Mgr family, contains Fe-S cluster CAETHG_1625, CAETHG_2284 CUU_c01810, CUU_c37780 CLRAG_37200 1992 phosphatidate cytidylyltransferase 2.7.7.41 CAETHG_3390 CUU_cl3070 CLRAG_10720 1993 ADP-ribose pyrophosphatase YjhB family NUDIX CAETHG_0525 CUU_c24610 CLRAG_18320 1994 dATP pyrophosphohydrolase CAETHG_0527 CUU_c24630 CLRAG_29990 1995 ADP-ribose pyrophosphatase YjhB family NUDIX CAETHG_3606 CUU_cl5020 CLRAG_24330 1996 NUDIX domain-containing protein CAETHG_3872 CUU_cl7640 CLRAG_01100 1997 Predicted O-methyltransferase YrrM CAETHG_3305 CUU_cl2230 CLRAG_11570 1998 GTP binding protein CAETHG_2831 CUU_c07390 CLRAG_26450 1999 YgeW carbamoyltransferase containing a knot domain CAETHG_0449 CUU_c23840 CLRAG_17330 2000 Uncharacterized OsmC-related protein CAETHG_0003 CUU_cl9270 CLRAG_39790 2001 two-component system of the OmpR family, sensor histidine kinase KdpD CAETHG_1797 CUU_c39520 CLRAG_21720 2002 Predicted oxidoreductase of the aldo/ketoreductase family CAETHG_1059 CUU_c30540 CLRAG_15970 2003 nitroreductase CAETHG_1146 CUU_c32180 CLRAG_02810 2004 Glycine/O-amino acid oxidase (deamination) CAETHG_1255 CUU_c33560 CLRAG_24720 2005 sarcosine oxidase, alpha subunit 1.5.3.1 CAETHG_1599 CUU_c37470 CLRAG_36880 2006 threonylcarbamoyladenosine-tRNA methylthiotransferase MtaB CAETHG_2896 CUU_c08020 CLRAG_08340 2007 NADPH-dependent glutamate synthase, beta chain CAETHG_2963 CUU_c08690 CLRAG_07800 2008 NAD(P)H-flavin reductase CAETHG_3965 CUU_cl8580 CLRAG_00120 2009 putative selenate reductase CAETHG_0448 CUU_c23830 CLRAG_17340 2010 carbon monooxide dehydrogenase, small subunit 1.1.1.204, 1.17.1.4 CAETHG_0455, CAETHG_0992 CUU_c29930, CUU_c23890 CLRAG_17270 2011 DNA-binding transcriptional regulator of the PadR family CAETHG_1380 CUU_c34820 CLRAG_26060 2012 penicillin binding protein 2 CAETHG_0109, CAETHG_2817 CUU_c07250, CUU_c20280 CLRAG_26010 2013 Blal family transcription regulator, penicillinase repressor CAETHG_1721, CAETHG_2769 CUU_c38720, CUU_c06780 CLRAG_18580 2014 E-aminopeptidase/O-esterase CAETHG_0849 CUU_c28550 CLRAG_34620 2015 Zn-dependent protease (contains SpolVFB) CAETHG_0966 CUU_c29680 CLRAG_35680 2016 hypothetical protein CAETHG_1592 CUU_c37360 CLRAG_36800 2017 Cell fate regulator YaaT of the PSP1 superfamily (controls sporulation, competence, biofilm development) CAETHG_2248 CUU_c01420 CLRAG_27080 2018 spore coat assembly protein CAETHG_2311 CUU_c02060 CLRAG_27660 2019 Murein-OO-endopeptidase MerM and murein hydrolase activator NIpD, containing a LysM domain CAETHG_2354 CUU_cO248O CLRAG_28090

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2020 hypothetical protein CAETHG_2565 CUU_cO488O CLRAG_38270 2021 S41 family peptidase CAETHG_3718 CUU_cl6240 CLRAG_33150 2022 S51 family peptidase CAETHG_1074 CUU_c30700 CLRAG_16130 2023 peptide/nickel transport system, substrate-binding protein CAETHG_1550 CUU_c36890 CLRAG_36420 2024 Cell division protein Ftsl/penicillin binding protein 2 CAETHG_3307 CUU_cl2250 CLRAG_11550 2025 peptidoglycan glycosyltransferase CAETHG_2430 CUU_cO315O CLRAG_28760 2026 hypothetical protein CAETHG_0014 CUU_cl9370 CLRAG_39720 2027 hypothetical protein CAETHG_0121 CUU_c20380 CLRAG_25910 2028 ABC-2 transport system permease protein CAETHG_0355 CUU_c22930 CLRAG_01860 2029 ABC-2 transport system permease protein CAETHG_0356 CUU_c22940 CLRAG_01850 2030 NNP family MFS transporter, nitrate/nitrite transporter CAETHG_0438 CUU_c23740 CLRAG_17430 2031 putative AGZA family MFS transporter, xanthine/uracil permease CAETHG_0461, CAETHG_2941 CUU_cO848O, CUU_c23950 CLRAG_17210 2032 Predicted PurR-regulated permease RegM CAETHG_0571 CUU_c25030 CLRAG_17750 2033 ABC transport system, putative permease protein CAETHG_0647 CUU_c25780 CLRAG_04010 2034 hypothetical protein CAETHG_0729 CUU_c26480 CLRAG_04570 2035 ABC transport system, putative permease protein CAETHG_0805 CUU_c27200 CLRAG_20030 2036 ABC transport system, putative permease protein CAETHG_1015 CUU_c30150 CLRAG_15730 2037 Drug/metabolite transporter (DMT) superfamily permease CAETHG_1141 CUU_c32130 CLRAG_02760 2038 Predicted MFS family arabinose efflux permease CAETHG_1151, CAETHG_2911 CLJU_c32230, CUU_cO816O CLRAG_03050 2039 Fucose permease CAETHG_1181 CUU_c32830 CLRAG_15500 2040 hypothetical protein CAETHG_1230 CUU_c33310 CLRAG_14950 2041 ABC-2 family transport protein CAETHG_1583 CUU_c37270 CLRAG_36710 2042 ABC transport system, putative permease protein CAETHG_1712 CUU_c38620 CLRAG_20940 2043 MFS DHA2 family transporter, clincomycin resistance protein CAETHG_2540 CUU_cO468O CLRAG_38060 2044 Predicted MFS family arabinose efflux permease CAETHG_2545 CUU_c04730 CLRAG_38110 2045 Drug/metabolite transporter (DMT) superfamily permease CAETHG_2748 CUU_cO658O CLRAG_18390 2046 ABC-2 transport system permease protein CAETHG_3009 CUU_cO915O CLRAG_13880 2047 ABC-2 transport system permease protein CAETHG_3010 CUU_cO916O CLRAG_13870 2048 hypothetical protein CAETHG_3271 CUU_cll800 CLRAG_11740 2049 Predicted PurR-regulated permease RegM CAETHG_3296 CUU_cl2140 CLRAG_11660 2050 hypothetical protein CAETHG_3463 CUU_cl3800 CLRAG_10040 2051 ABC transport system, putative permease protein CAETHG_3511 CUU_cl4290 CLRAG_09650 2052 putative membrane protein CAETHG_1135 CUU_c32070 CLRAG_02700 2053 putative membrane protein CAETHG_1136 CUU_c32080 CLRAG_02710 2054 N-terminal YhgE/Pip domain-containing protein / C-terminal YhgE/Pip domain-containing protein CAETHG_1232 CUU_c33330 CLRAG_14930 2055 DNA polymerase CAETHG_2274 CUU_cO172O CLRAG_27320

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2056 chorismate mutase CAETHG_2806 CUU_c07140 CLRAG_26700 2057 Inositol hexa-kis-phosphate CAETHG_1137, CAETHG_1698 CUU_c38430, CUU_c32090 CLRAG_08920 2058 undecaprenide diphosphatase CAETHG_1152, CAETHG_3691 CUU_c32240, CUU_cl5820 CLRAG_03120 2059 PAP2 superfamily protein CAETHG_1683 CUU_c38260 CLRAG_20730 2060 phosphoglycolate phosphatase 3.2.2.16, 3.2.2.9 CAETHG_2493 CUU_c04250 CLRAG_26780 2061 undecaprenide diphosphatase CAETHG_3695 CUU_cl5960 CLRAG_22200 2062 phosphoglycolate phosphatase 3.2.2.16, 3.2.2.9 CAETHG_3886 CUU_cl7780 CLRAG_00930 2063 inorganic phosphate transporter PiT family CAETHG_3327 CUU_cl2450 CLRAG_11350 2064 two-component system, OmpR family, sensor histidine kinase of the phosphate regulon PhoR CAETHG_3320 CUU_cl2380 CLRAG_11420 2065 PhoH-like ATPase CAETHG_0969 CUU_c29710 CLRAG_35710 2066 phosphate transport system protein CAETHG_3325 CUU_cl2430 CLRAG_11370 2067 phosphorus transport protein CAETHG_3418 CUU_cl3350 CLRAG_10440 2068 hypothetical protein CAETHG_1545 CUU_c36840 CLRAG_36370 2069 MJ0936 family phosphoesterase CAETHG_2564 CUU_c04870 CLRAG_38260 2070 phosphoesterase domain-containing protein RecJ CAETHG_3400 CUU_cl3170 CLRAG_10620 2071 putative hydrolase CAETHG_1250 CUU_c33510 CLRAG_24770 2072 Phosphoglycerate dehydrogenase 1.1.1.95 CAETHG_2039 CUU_c42090 CLRAG_05200 2073 probable phosphoglycerate mutase 5.4.2.11 CAETHG_0712 CUU_c26320 CLRAG_04410 2074 3',5'-cAMP phosphodiesterase CpdA CAETHG_1521 CUU_c36110 CLRAG_06640 2075 hypothetical protein CAETHG_2374 CUU_c02720 CLRAG_28320 2076 Predicted phosphoribosyltransferase CAETHG_0721 CUU_c26400 CLRAG_04490 2077 dTDP-4-amino-4,6- dideoxygalactose transaminase CAETHG_0760 CUU_c26790 CLRAG_08660 2078 O-acetyl-ADP-riboseacetylase (regulator RNase III), contains a macrodomain CAETHG_2691 CUU_c05940 CLRAG_07170 2079 uOP-N-acetylglucosamine-4,6-dehydratase (inverting) CAETHG_2630 CUU_c05480 CLRAG_38940 2080 pseudoamic acid synthase 4.1.3.19, 2.5.1.56 CAETHG_2633 CUU_c05510 CLRAG_38970 2081 UDP-2,4-diacetamido-2,4,6-trideoxy-beta-1_altropyranose hydrolase 2.7.7.43 CAETHG_2634 CUU_c05520 CLRAG_38980 2082 Membrane protein involved in the export of Oantigen and teichoic acid CAETHG_2635 CUU_c05530 CLRAG_38990 2083 protein SpsF biosynthesis of spore membrane polysaccharide 2.7.7.38 CAETHG_2632 CUU_c05500 CLRAG_38960 2084 Peptidoglya n/xyl n/chitinde cetylase of the PgdA/CDAl family CAETHG_0754 CUU_c26730 CLRAG_08600 2085 Peptidoglya n/xyl n/chitinde cetylase of the PgdA/CDAl family CAETHG_0834, CAETHG_1697 CUU_c38420, CUU_c28370 CLRAG_34450 2086 peptidoglycan-N-deacetylase acetylmuramic acid CAETHG_1297 CUU_c33990 CLRAG_14140 2087 Peptidoglya n/xyl n/chitinde cetylase of the PgdA/CDAl family CAETHG_1864, CAETHG_2718 CUU_c40160, CUU_c06180 CLRAG_07460 2088 Peptidoglya n/xyl n/chitinde cetylase of the PgdA/CDAl family CAETHG_2265 CUU_c01600 CLRAG_27250 2089 Polysaccharide deacetylase CAETHG_2266 CUU_c01610 CLRAG_27260 2090 translocase preprotein, SecE subunit CAETHG_1961 CUU_c41180 CLRAG_23370 2091 putative protease CAETHG_1339 CUU_c34390 CLRAG_14470 2092 YeaZ protein threonylcarbamoyladenosine modification of tRNA CAETHG_1675 CUU_c38190 CLRAG_20650

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2093 C-terminal processing protease CAETHG_2424 CLJU_cO3O9O CLRAG_28700 2094 C-terminal processing protease CAETHG_2703 CLJU_c06040 CLRAG_07310 2095 hypothetical protein CAETHG_2704 CUU_c06050 CLRAG_07320 2096 4-methyl-5 (L-hydroxyethyl)thiazole monophosphate biosynthesis protein CAETHG_3016 CLJU_cO922O CLRAG_13810 2097 putative protease CAETHG_3306 CUU_cl2240 CLRAG_11560 2098 ATP-dependent protease C1pP, protease subunit CAETHG_3407 CUU_cl3240 CLRAG_10550 2099 hypothetical protein CAETHG_3600 CUU_cl4960 CLRAG_24390 2100 serpin B CAETHG_3677 CUU_cl5690 CLRAG_32850 2101 M28 family peptidase CAETHG_2368 CUU_c02670 CLRAG_28270 2102 protein phosphatase CAETHG_3343 CUU_cl2610 CLRAG_11190 2103 Protein containing a PAS domain with an S box CAETHG_2404 CUU_c02890 CLRAG_28490 2104 translocase preprotein, SecF subunit CAETHG_1272 CUU_c33740 CLRAG_24540 2105 translocase preprotein, SecD subunit CAETHG_1273 CUU_c33750 CLRAG_24530 2106 purine catabolism regulatory protein CAETHG_0433 CUU_c23690 CLRAG_17480 2107 Cytidine and deoxycytidylate deaminase, zinc-binding region 3.5.4.1 CAETHG_0990 CUU_c29910 CLRAG_35910 2108 NAD+-diphosphatase CAETHG_0028 CUU_cl9510 CLRAG_39600 2109 Pyrimidine operon attenuation protein/uracil phosphoribosyltransferase 2.4.2.9 CAETHG_3164 CUU_cl0740 CLRAG_12600 2110 enzyme that activates pyruvate formate lyase CAETHG_3449 CUU_cl3670 CLRAG_10200 2111 4-hydroxytetrahydrodipicolinate synthase 4.2.1.52 CAETHG_2178 CUU_c00600 CLRAG_19980 2112 uncharacterized protein YgiQ, containing the SAM radical CAETHG_2411 CUU_c02960 CLRAG_28570 2113 GTP-binding protein Era CAETHG_2905 CUU_c08100 CLRAG_08250 2114 fumarate reductase, flavoprotein subunit 1.3.99.1 CAETHG_2961 CUU_c08670 CLRAG_07820 2115 transcriptional regulator of the ABrB family CAETHG_2257 CUU_c01510 CLRAG_27170 2116 DNA-binding transcription activator of the SARP family CAETHG_0235 CUU_c21490 CLRAG_31050 2117 PucR protein containing a C-terminal helix-loop-helix domain CAETHG_1081 CUU_c30770 CLRAG_16210 2118 regulatory protein CAETHG_1448 CLJU_c35400 CLRAG_05940 2119 regulatory protein blaRl CAETHG_3432 CUU_cl3480 CLRAG_10310 2120 regulatory protein blaRl CAETHG_4027 CUU_cl8930 CLRAG_40040 2121 site-specific DNA recombinase CAETHG_1440, CAETHG_3959 CLJU_c35310, CUU_cl8520 CLRAG_05840 2122 DNA-binding response regulator of the OmpR family, contains a REC and a winged helix domain (wHTH) CAETHG_0061 CUU_cl9810 CLRAG_39270 2123 diguanylate cyclase domain-containing protein (GGDEF) CAETHG_1072 CUU_c30680 CLRAG_16100 2124 DNA-binding response regulator of the OmpR family, contains a REC and a winged helix domain (wHTH) CAETHG_2216 CLJU_c01050 CLRAG_30350 2125 pili assembly protein CpaE CAETHG_0878 CUU_c28820 CLRAG_34900 2126 membrane protein CAETHG_1777 CUU_c39320 CLRAG_21530 2127 ribonuclease G CAETHG_2827 CUU_c07350 CLRAG_26490 2128 ribonuclease HI CAETHG_2712 CUU_c06130 CLRAG_07410 2129 ribonuclease R CAETHG_1754 CLJU_c39090 CLRAG_21240 2130 23S rRNA pseudouridine955/2504/2580 synthase 4.2.1.70 CAETHG_3848 CUU_cl7350 CLRAG_29230 2131 Ribosomal protein L7Ae CAETHG_3397 CUU_cl3140 CLRAG_10650

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2132 ribosome recycling factor CAETHG_3388 CUU_cl3050 CLRAG_10740 2133 ATP-dependent RNA helicase DeaD CAETHG_1450 CUU_c35420 CLRAG_05960 2134 RNA polymerase sigma factor 70 ECF subfamilies CAETHG_0730 CUU_c26490 CLRAG_08370 2135 Sigma factor RNA polymerase family sigma-70 CAETHG_2597 CUU_cO52OO CLRAG_38590 2136 RNA polymerase sigma factor 70 ECF subfamilies CAETHG_2772 CUU_c06810 CLRAG_18610 2137 RNA polymerase sigma factor 70 ECF subfamilies CAETHG_3440 CUU_cl3570 CLRAG_10290 2138 Sigma factor RNA polymerase family sigma-70 CAETHG_0660 CUU_c25910 CLRAG_04050 2139 hypothetical protein CAETHG_1965 CUU_c41240 CLRAG_23430 2140 spolllJ associated protein CAETHG_2119 CUU_c42930 CLRAG_25740 2141 RNA binding protein YlmH, contains a 54-like domain CAETHG_3158 CUU_cl0680 CLRAG_12660 2142 Predicted component of the ribosome quality control complex (RQC) of the YloA/Tae2 family, contains a fibronectin-binding domain (FbpA) and a DUF814 domain CAETHG_3165 CUU_cl0750 CLRAG_12590 2143 Protein containing S1 RNA-binding domain CAETHG_1991 CUU_c41620 CLRAG_04750 2144 Na+-translocating ferredoxin: NAD+- RNF oxidoreductase, RnfC subunit 1.16.1.4 CAETHG_1823 CUU_c39770 CLRAG_22020 2145 protein MreD, which determines the shape of the rod CAETHG_2816 CUU_c07240 CLRAG_26600 2146 MheC protein, which determines the shape of the rod CAETHG_2815 CUU_c07230 CLRAG_26610 2147 RodA protein, which determines the shape of the rod CAETHG_2821 CUU_c07290 CLRAG_26550 2148 Putative rRNA methylase CAETHG_0413 CUU_c23490 CLRAG_17620 2149 RNA methyltransferase of the TgtH family CAETHG_1343 CUU_c34430 CLRAG_14510 2150 tRNA(cytidine/uridine-2'-O-)-methyltransferase CAETHG_1764 CUU_c39190 CLRAG_21340 2151 23S rRNA-(guanosine2251-2'-O)- methyltransferase CAETHG_1966 CUU_c41250 CLRAG_23440 2152 23S rRNA-(cytidine1920-2'-0)/165 rRNA- (cytidine1409-2'-0)-methyltransferase CAETHG_3206 CUU_clll70 CLRAG_12290 2153 16S rRNA-(cytosine967-C5)-methyltransferase CAETHG_3341 CUU_cl2590 CLRAG_11210 2154 Rubrerythrin CAETHG_0664 CUU_c25950 CLRAG_04090 2155 Rubrerythrin CAETHG_0887 CUU_c28910 CLRAG_34990 2156 Rubrerythrin CAETHG_1779 CUU_c39340 CLRAG_21550 2157 Rubrerythrin CAETHG_1791 CUU_c39460 CLRAG_21670 2158 Rubrerythrin CAETHG_3813 CUU_cl7010 CLRAG_33880 2159 16S rRNA-(cytosine1402-N4)-methyltransferase CAETHG_3144 CUU_cl0540 CLRAG_12800 2160 2-polyprenyl-3-methyl-5-hydroxy-6-methoxy1,4-benzoquinol methylase CAETHG_1355 CUU_c34590 CLRAG_14670 2161 Heat shock protein, involved in recycling of the 505 ribosomal subunit, contains an S4 domain CAETHG_1995 CUU_c41660 CLRAG_04790 2162 Protein containing a methyltransferase domain CAETHG_0944 CUU_c29500 CLRAG_35490 2163 Trans-aconitate methyltransferase CAETHG_3173 CLJU_cl0840 CLRAG_03140 2164 RND family efflux transporter, MFP subunit CAETHG_0390 CUU_c23270 CLRAG_01460 2165 secretion protein of the HlyD family CAETHG_2506, CAETHG_2693 CLJU_c04380, CUU_c05960 CLRAG_37710 2166 RND family efflux transporter, MFP subunit CAETHG_2471, CAETHG_2852 CLJU_cO759O, CUU_cO4O8O CLRAG_29190 2167 Protein containing His kinase A (phosphoacceptor) domain CAETHG_2515 CUU_c04430 CLRAG_37790

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2168 Histidine signaling kinase CAETHG_2786 CUU_c06960 CLRAG_18800 2169 Protein containing a PAS domain with an S box CAETHG_1004 CLJU_c30050 CLRAG_15680 2170 Histidine signaling kinase CAETHG_2550 CUU_c04780 CLRAG_38160 2171 Protein containing a PAS domain with an S box CAETHG_0056 CUU_cl9760 CLRAG_39380 2172 HAMP domain-containing protein CAETHG_0577 CUU_c25090 CLRAG_17680 2173 DNA-binding response regulator of the OmpR family, contains a REC and a winged helix domain (wHTH) CAETHG_0803 CUU_c27180 CLRAG_20050 2174 Histidine signaling kinase CAETHG_1013 CUU_c30130 CLRAG_15710 2175 Protein containing His kinase A (phosphoacceptor) domain CAETHG_1068 CLJU_c30640 CLRAG_16070 2176 Histidine signaling kinase CAETHG_1714 CUU_c38640 CLRAG_20960 2177 Histidine signaling kinase CAETHG_1872 CUU_c40260 CLRAG_07650 2178 HAMP domain-containing protein CAETHG_2004 CUU_c41750 CLRAG_04880 2179 Histidine signaling kinase CAETHG_2217 CUU_c01060 CLRAG_30340 2180 Protein containing His kinase A (phosphoacceptor) domain CAETHG_3460 CUU_cl3770 CLRAG_10070 2181 Histidine signaling kinase CAETHG_3602 CUU_cl4980 CLRAG_24370 2182 DNA-binding response regulator of the OmpR family, contains a REC and a winged helix domain (wHTH) CAETHG_2005 CUU_c41760 CLRAG_04890 2183 diguanylate cyclase domain-containing protein (GGDEF) CAETHG_2642 CUU_c05600 CLRAG_06730 2184 topological specificity factor cell division CAETHG_2820 CUU_c07280 CLRAG_26560 2185 protein MinD, which determines the location of the septum CAETHG_2819 CUU_cO727O CLRAG_26570 2186 serine protease Do CAETHG_2003 CUU_c41740 CLRAG_04870 2187 serine protease Do CAETHG_2936 CUU_c08430 CLRAG_08030 2188 putative serine protein kinase, PrkA CAETHG_2503 CLJU_c04350 CLRAG_37680 2189 L isophospholipase L1 CAETHG_1718, CAETHG_2934 CLJU_c38700, CLJU_c08400 CLRAG_08050 2190 NADP-dependent dehydrogenase 3- hydroxy acids YdfG CAETHG_3497 CUU_cl4160 CLRAG_09480 2191 hypothetical protein 2.3.1.85, 2.3.1.86, 1.1.1.100, 1.1.1.0 CAETHG_0180 CUU_c20960 CLRAG_19060 2192 3-oxoacyl-[acyl carrier protein group]-reductase 2.3.1.85, 2.3.1.86, 1.1.1.100, 1.1.1.0 CAETHG_0914 CUU_c29220 CLRAG_35220 2193 hypothetical protein 2.3.1.85, 2.3.1.86, 1.1.1.100, 1.1.1.0 CAETHG_0739 CUU_c26580 CLRAG_08450 2194 RNA polymerase sigma factor 70 ECF subfamilies CAETHG_3678 CUU_cl5700 CLRAG_32860 2195 RNA polymerase sigma factor 70 ECF subfamilies CAETHG_2488 CLJU_c04200 CLRAG_26860 2196 Metabolic transcription regulator acetoin/glycerol CAETHG_0386, CAETHG_2800 CLJU_c23230 CLRAG_01500 2197 diguanylate cyclase domain-containing protein (GGDEF) CAETHG_3871 CUU_cl7630 CLRAG_01110 2198 signal peptidase II CAETHG_3161 CLJU_clO71O CLRAG_12630 2199 two-component system of the chemotaxis protein family, response regulator CheY CAETHG_1003 CLJU_c30040 CLRAG_15670 2200 two-component protein family system CAETHG_3429 CUU_cl3450 CLRAG_10340

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chemotaxis, response regulator CheY 2201 Histidine signaling kinase CAETHG_0023 CUU_cl9460 CLRAG_39650 2202 Histidine signaling kinase CAETHG_0040 CUU_cl9630 CLRAG_39510 2203 Histidine signaling kinase CAETHG_0062 CUU_cl9820 CLRAG_39260 2204 hypothetical protein CAETHG_2528 CUU_c04560 CLRAG_37920 2205 Signaling protein containing EAL and a modified HD-GYP domain CAETHG_0011 CUU_cl9340 CLRAG_39750 2206 PAS domain-containing protein and S-box/diguanylate cyclase domain-containing protein (GGDEF) CAETHG_1070 CUU_c30660 CLRAG_16080 2207 PAS domain-containing protein and S-box/diguanylate cyclase domain-containing protein (GGDEF) CAETHG_3969 CUU_cl8610 CLRAG_00040 2208 c-di-AMP phosphodiesterase, consists of GGDEF-like domains and DHH domains CAETHG_2099 CUU_c42740 CLRAG_25550 2209 Single-stranded DNA binding protein CAETHG_1358 CUU_c34620 CLRAG_14700 2210 phosphoesterase domain-containing protein RecJ CAETHG_1271 CUU_c33730 CLRAG_24550 2211 selenium metabolism protein YedF CAETHG_0224 CUU_c21380 CLRAG_30940 2212 Site-specific recombinase XerD CAETHG_0186 CUU_c21010 CLRAG_19010 2213 Small acid-soluble alpha/beta spore protein CAETHG_0276, CAETHG_0853 CUU_c28580, CUU_c21860 CLRAG_34650 2214 Small acid-soluble alpha/beta spore protein CAETHG_0541 CUU_c24760 CLRAG_18060 2215 Small acid-soluble alpha/beta spore protein CAETHG_0971 CUU_c30960, CUU_c29720 CLRAG_35720 2216 small acid-soluble protein spore H (minor) CAETHG_0980 CUU_c29810 CLRAG_35820 2217 Small acid-soluble alpha/beta spore protein CAETHG_1354 CUU_c34580 CLRAG_14660 2218 DNA processing protein CAETHG_3382 CUU_cl2990 CLRAG_10800 2219 small multidrug resistance pump CAETHG_3645 CUU_cl5440 CLRAG_32570 2220 DNA or RNA helicase superfamily II, SNF2 family CAETHG_0242 CUU_c21550 CLRAG_31110 2221 proton-glutamate symport protein CAETHG_0164 CUU_c20790 CLRAG_19210 2222 solute symporter:Na+ SSS family CAETHG_1185 CUU_c32870 CLRAG_15460 2223 solute symporter:Na+ SSS family CAETHG_3470 CUU_cl3870 CLRAG_09970 2224 symporter of divalent anions:Na+ of the DASS family CAETHG_0819 CUU_c28190 CLRAG_09140 2225 chromosome separation protein of the PahrB family CAETHG_2113 CUU_c42870 CLRAG_25680 2226 JB spore coat protein CAETHG_1241 CUU_c33410 CLRAG_14840 2227 dTDP-4-amino-4,6- dideoxygalactose transaminase CAETHG_0759 CUU_c26780 CLRAG_08650 2228 Coat protein containing F domain CAETHG_1253 CUU_c33540 CLRAG_24740 2229 spore coat protein of the CotS family CAETHG_2304 CUU_c02000 CLRAG_27600 2230 hypothetical protein CAETHG_2306 CUU_c02020 CLRAG_27620 2231 spore coat protein of the CotS family CAETHG_2308 CUU_c02030 CLRAG_27630 2232 spore coat-associated protein S CAETHG_2310 CUU_c02050 CLRAG_27650 2233 spore coat protein of the CotS family CAETHG_2915 CUU_c08200 CLRAG_08190 2234 spore coat protein JC CAETHG_1242 CUU_c33420 CLRAG_14830 2235 CotF spore coat protein CAETHG_0978 CUU_c29790 CLRAG_35790 2236 Coat protein containing F domain CAETHG_2174 CUU_c00560 CLRAG_20010 2237 CA spore germination protein CAETHG_1503 CUU_c35950 CLRAG_06450

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2238 Ger(x)C family germination protein CAETHG_1504 CUU_c35960 CLRAG_06460 2239 spore germination protein (permease) amino acids) CAETHG_1506 CUU_c35980 CLRAG_06480 2240 spore germination protein KB CAETHG_3738 CUU_cl6440, CUU_cl6460 CLRAG_33240 2241 KS spore germination protein CAETHG_3743 CUU_cl6480 CLRAG_33260 2242 CA spore germination protein CAETHG_3744 CUU_cl6490 CLRAG_33270 2243 Ger(x)C family germination protein CAETHG_3951 CUU_cl8440 CLRAG_00240 2244 spore germination protein (permease) amino acids) CAETHG_3952 CUU_cl8450 CLRAG_00230 2245 spore germination protein GerA CAETHG_3953 CUU_cl8460 CLRAG_00220 2246 spore germination protein CAETHG_2318 CUU_c02130 CLRAG_27730 2247 spore germination protein (permease) amino acids)/germination protein of the Ger(x)C family CAETHG_2319 CUU_c02140 CLRAG_27740 2248 protein A spore maturation CAETHG_2272 CUU_c01700 CLRAG_27300 2249 protein in spore maturation CAETHG_2273 CLJU_cO171O CLRAG_27310 2250 photoproduct lyase spores 4.1.99,- CAETHG_1200 CUU_c33020 CLRAG_15310 2251 sporulation stage II protein GA (sporulation factor processing peptidase sigma-E) CAETHG_3313 CUU_cl2310 CLRAG_11490 2252 integral membrane protein of sporulation YlbJ CAETHG_3355 CUU_cl2740 CLRAG_11070 2253 germination protein YpeB CAETHG_2322 CUU_c02170 CLRAG_27770 2254 sporulation protein of the YlmC/YmxH family CAETHG_3316 CUU_cl2340 CLRAG_11460 2255 SsrA-binding protein CAETHG_1753 CUU_c39080 CLRAG_21230 2256 stage II sporulation protein D CAETHG_2353 CUU_c02470 CLRAG_28080 2257 protein E of stage II sporulation CAETHG_1990 CUU_c41560 CLRAG_04690 2258 protein M stage II of sporulation CAETHG_3215 CUU_cll250 CLRAG_12210 2259 protein P of stage II of sporulation CAETHG_2885 CLJU_cO792O CLRAG_25400 2260 stage II sporulation protein R CAETHG_2320 CUU_c02150 CLRAG_27750 2261 protein AA stage III sporulation CAETHG_3192 CUU_cll030 CLRAG_12430 2262 AB protein of stage III sporulation CAETHG_3193 CUU_cll040 CLRAG_12420 2263 AS protein of stage III of sporulation CAETHG_3194 CUU_cll050 CLRAG_12410 2264 Sporulation stage III AD protein CAETHG_3195 CUU_cll060 CLRAG_12400 2265 protein AE stage III sporulation CAETHG_3196 CUU_cll070 CLRAG_12390 2266 sporulation stage III AF protein CAETHG_3197 CUU_cll080 CLRAG_12380 2267 sporulation stage III AG protein CAETHG_3198 CUU_cllO9O CLRAG_12370 2268 AN protein of stage III sporulation CAETHG_3199 CUU_clll00 CLRAG_12360 2269 protein In stage IV of sporulation CAETHG_3211 CUU_cll210 CLRAG_12250 2270 sporulation stage IV FB protein CAETHG_2824 CUU_c07320 CLRAG_26520 2271 sporulation stage V AC protein CAETHG_0176 CUU_c20910 CLRAG_19100 2272 sporulation stage V protein AE CAETHG_0178 CUU_c20940 CLRAG_19080 2273 protein In stage IV of sporulation CAETHG_0303 CUU_c22050 CLRAG_31570 2274 protein In stage IV of sporulation CAETHG_1998 CUU_c41690 CLRAG_04820 2275 protein In stage V of sporulation CAETHG_3849 CUU_cl7360 CLRAG_29220 2276 sporulation stage V protein G CAETHG_2008 CUU_c41790 CLRAG_04920 2277 stage V sporulation protein R CAETHG_2501 CUU_c04330 CLRAG_37660 2278 SP family MFS transporter, major inositol transporter CAETHG_3686 CUU_cl5780 CLRAG_32940 2279 Subtilase family protein CAETHG_2038 CUU_c42080 CLRAG_05190 2280 methyl galactoside transport system, substrate binding protein CAETHG_2989 CUU_c08950 CLRAG_07550

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2281 carbohydrate diacid regulator CAETHG_0822 CUU_c28220 CLRAG_09170 2282 protein A stimulates the fermentation of sugars CAETHG_2204 CLJU_cOO9OO CLRAG_19680 2283 NAD(P)H-hydratepimerase CAETHG_2416 CUU_c03010 CLRAG_28620 2284 Sugar phosphate isomerase/epimerase CAETHG_1474 CUU_c35660 CLRAG_06190 2285 glucuronide transport protein CAETHG_0138 CUU_c20550 CLRAG_19440 2286 Phosphoglycerol transferase MdoB CAETHG_0576, CAETHG_2971 CLJU_c25080, CUU_c08770 CLRAG_17690 2287 Putative cell wall binding protein containing repeat 2 CAETHG_0972 CUU_c29730 CLRAG_35730 2288 Putative cell wall binding protein containing repeat 2 3.5.1.28 CAETHG_2558, CAETHG_2576 CLJU_c04990 CLRAG_38380 2289 lg-like domain (group 4) CAETHG_2681 CUU_c05860 CLRAG_07100 2290 lg-like domain (group 4) CAETHG_3096 CUU_cl0060 CLRAG_13310 2291 lg-like domain (group 4) CAETHG_3097 CUU_clOO7O CLRAG_13300 2292 solute symporter:Na+ SSS family CAETHG_0381 CUU_c23180 CLRAG_01550 2293 Thiamine biosynthetic protein Thil CAETHG_0832 CUU_c28350 CLRAG_34430 2294 thiamine biosynthesis lipoprotein CAETHG_1459 CUU_c35510 CLRAG_06040 2295 acyl-CoA thioester hydrolase 3.1.2. CAETHG_1524 CUU_c36140 CLRAG_06660 2296 Predicted transcriptional regulator YdeE, contains an AgaC-type DNA-binding domain CAETHG_3624 CUU_cl5220 CLRAG_24130 2297 DNA gyrase inhibitor Gyri CAETHG_3857 CUU_cl7440 CLRAG_01270 2298 transcription elongation factor GreA CAETHG_0720 CUU_c26390 CLRAG_04480 2299 transcription elongation factor GreA CAETHG_1453 CUU_c35450 CLRAG_05980 2300 transcription elongation factor GreA CAETHG_1983 CUU_c41490 CLRAG_04620 2301 Large subunit of hydrogenase containing an iron atom, C-terminal domain CAETHG_0119 CUU_c20370 CLRAG_25920 2302 PucR protein containing a C-terminal helix-loop-helix domain CAETHG_0128 CUU_c20460 CLRAG_19560 2303 DNA-binding transcriptional regulator of the PucR family CAETHG_0158 CUU_c20730 CLRAG_19270 2304 GntR family transcriptional regulator, transcriptional repressor for the pyruvate dehydrogenase complex CAETHG_0249 CUU_c21620 CLRAG_31210 2305 putative transcriptional regulator CAETHG_0545, CAETHG_3487 CUU_c24800, CUU_cl4060 CLRAG_17990 2306 DNA-binding transcriptional regulator of the PadR family CAETHG_0562 CUU_c24950 CLRAG_17830 2307 DNA-binding transcription regulator YhcF family GntR CAETHG_0581 CUU_c25130 CLRAG_03470 2308 thiaminase (transcription activator TepA) CAETHG_0610 CUU_c25410 CLRAG_03690 2309 DNA-binding response regulator of the OmpR family, contains a REC and a winged helix domain (wHTH) CAETHG_0644, CAETHG_1715 CUU_c38650, CUU_c25750 CLRAG_20970 2310 Protein containing a helix-loop-helix domain CAETHG_0746 CUU_c26650 CLRAG_08520 2311 protein of the ABrB family containing a DNA-binding loop-helix domain CAETHG_0771 CUU_c26870 CLRAG_16110 2312 Response regulator receiver domain-containing protein CAETHG_0913 CUU_c29210 CLRAG_35210 2313 DNA-binding response regulator of the OmpR family, contains a REC and a winged helix domain (wHTH) CAETHG_1014, CAETHG_3461 CUU_cl3780, CUU_c30140 CLRAG_15720 2314 putative transcriptional regulator CAETHG_1179, CAETHG_3956 CUU_cl8490, CUU_c32810 CLRAG_15520 2315 DNA-binding transcriptional regulator of the PadR family CAETHG_1191 CUU_c32930 CLRAG_15400 2316 DNA-binding transcription regulator 2.6.1.23, CAETHG_1287 CUU_c33890 CLRAG_14040

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MocR family, contains aminotransferase domain 2.6.1.1 2317 DNA-binding transcriptional regulator of the MerR family CAETHG_1416 CUU_c35070 CLRAG_26330 2318 GntR family transcription regulator CAETHG_1438 CUU_c35290 CLRAG_05820 2319 Predicted DNA-binding transcriptional regulator YafY, contains HTH and WYL domains CAETHG_1466 CUU_c35580 CLRAG_06110 2320 DNA-binding transcriptional regulator of the LysR family CAETHG_1627 CUU_c37800 CLRAG_37220 2321 central regulator of glycolysis genes CAETHG_1761 CUU_c39160 CLRAG_21310 2322 GntR family transcriptional regulator, abcA and norABC regulator 2.6.1.23, 2.6.1.1 CAETHG_1837 CUU_c39910 CLRAG_22160 2323 Helix-loop-helix domain CAETHG_2022 CUU_c41930 CLRAG_05040 2324 hypothetical protein CAETHG_2132 CUU_c00130 CLRAG_20190 2325 DNA-binding response regulator of the OmpR family, contains a REC and a winged helix domain (wHTH) CAETHG_2197 CUU_c00820 CLRAG_19760 2326 Fis family regulatory protein CAETHG_2443 CUU_c03810 CLRAG_28880 2327 GntR family transcription regulator CAETHG_2535 CUU_c04630 CLRAG_37990 2328 Tetratricopeptide repeat-containing protein CAETHG_2714 CUU_c06150 CLRAG_07430 2329 Tetratricopeptide repeat-containing protein CAETHG_2716 CUU_c06160 CLRAG_07440 2330 DNA-binding response regulator of the OmpR family, contains a REC and a winged helix domain (wHTH) CAETHG_2747 CUU_cO651O CLRAG_30390 2331 Transcription regulator of the Lrp/AsnC family, regulator of asnA, asnC and gid A CAETHG_2764 CUU_c06730 CLRAG_18530 2332 DNA-binding response regulator of the OmpR family, contains a REC and a winged helix domain (wHTH) CAETHG_2785 CUU_c06950 CLRAG_18790 2333 PucR protein containing a C-terminal helix-loop-helix domain CAETHG_2847 CUU_c07540 CLRAG_32330 2334 DNA-binding response regulator of the OmpR family, contains a REC and a winged helix domain (wHTH) CAETHG_2863 CUU_c07700 CLRAG_25240 2335 cAMP-binding domain of CRP or regulatory subunit of cAMP-dependent protein kinases CAETHG_2865 CUU_c07720 CLRAG_25260 2336 CBS domain-containing protein CAETHG_2908 CUU_c08130 CLRAG_08220 2337 DNA-binding transcriptional regulator of the MarR family CAETHG_2937 CUU_c08440 CLRAG_08020 2338 DNA-binding transcriptional regulator of the MerR family CAETHG_2964 CUU_c08700 CLRAG_07790 2339 DNA-binding transcriptional regulator of the MocR family, contains aminotransferase domain 2.6.1.23, 2.6.1.1 CAETHG_2980 CUU_c08850 CLRAG_07630 2340 transcriptional repressor NrdR CAETHG_3317 CUU_cl2350 CLRAG_11450 2341 two-component system of the OmpR family, regulator of the reaction to the synthesis of alkaline phosphatase PhoP CAETHG_3319 CUU_cl2370 CLRAG_11430 2342 arsenate reductase CAETHG_3456 CUU_cl3740 CLRAG_10110 2343 DNA-binding transcriptional regulator of the MerR family CAETHG_3493 CUU_cl4120 CLRAG_09460 2344 hypothetical protein CAETHG_3568 CUU_cl4680 CLRAG_20530 2345 PucR protein containing a C-terminal helix-loop-helix domain CAETHG_3605 CUU_cl5010 CLRAG_24340 2346 DNA-binding transcriptional regulator of the MarR family CAETHG_3618 CUU_cl5160 CLRAG_24190

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2347 Predicted DNA-binding transcriptional regulator YafY, contains HTH and WYL domains CAETHG_3623 CUU_cl5210 CLRAG_24140 2348 DNA-binding transcriptional regulator of the MerR family CAETHG_3652 CUU_cl5510 CLRAG_32590 2349 putative transcriptional regulator CAETHG_3870 CUU_cl7620 CLRAG_01120 2350 Blal family transcription regulator, penicillinase repressor CAETHG_4026 CUU_cl8920 CLRAG_40050 2351 DNA-binding transcriptional regulator of the MerR family CAETHG_1860 CLJU_c40110 CLRAG_22340 2352 Transcription regulator containing a PAS domain, an AAA-type ATPase domain, and a DNA-binding Fis domain CAETHG_1910 CUU_c40670 CLRAG_22860 2353 AgaC family transcription regulator CAETHG_2182 CLJU_c00640 CLRAG_19940 2354 transcriptional regulator CtsR CAETHG_1977 CUU_c41360 CLRAG_23550 2355 pleiotropic transcriptional repressor CAETHG_3384 CUU_cl3010 CLRAG_10780 2356 aspartate 4-decarboxylase CAETHG_1226 CUU_c33270 CLRAG_14990 2357 Protein containing transglycosylase SLT domain CAETHG_1562 CUU_c37010 CLRAG_36550 2358 L-threonylcarbamoyladenylate synthase CAETHG_2334 CUU_c02290 CLRAG_27890 2359 translation initiation factor IF-3 CAETHG_0161, CAETHG_1346 CLJU_c34460, CUU_c20760 CLRAG_19240 2360 hypothetical protein CAETHG_2810 CUU_c07180 CLRAG_26660 2361 MFS transporter of the DHA1 family, resistance protein bicyclomycin/chloramphenicol CAETHG_1485 CUU_c35770 CLRAG_06300 2362 Predicted MFS family arabinose efflux permease CAETHG_3508 CUU_cl4260 CLRAG_09580 2363 Predicted MFS family arabinose efflux permease CAETHG_3509 CUU_cl4270 CLRAG_09590 2364 Subfamily B protein of proteins containing an ATP-binding cassette CAETHG_0699 CUU_c26230 CLRAG_04350 2365 Subfamily B protein of proteins containing an ATP-binding cassette CAETHG_0700 CUU_c26240 CLRAG_04360 2366 Predicted MFS family arabinose efflux permease CAETHG_2981 CI_JU_c08860 CLRAG_07620 2367 substrate-binding protein of the transport system of the NitT/TauT family CAETHG_0734 CUU_c26530 CLRAG_08410 2368 MFS transporter, putative symporter of metabolites: H+ CAETHG_0198 CUU_c21120 CLRAG_30690 2369 MFS transporter, putative symporter of metabolites: H+ CAETHG_0200 CUU_c21140 CLRAG_30700 2370 Protein of the superfamily of major transporters involved in facilitated diffusion CAETHG_0565, CAETHG_1519 CUU_c36100, CUU_c24980 CLRAG_17800 2371 EmrB/QacA subfamily drug resistance transporter CAETHG_1177, CAETHG_1412 CLJU_c32790, CLJU_c35030 CLRAG_15570 2372 ABC-2 family transport protein CAETHG_1435, CAETHG_1436 CLJU_c35270, CUU_c35260 CLRAG_05790 2373 bacitracin transport system, permease protein CAETHG_2193 CUU_c00780 CLRAG_19800 2374 Multiple efflux pump drug resistance, AsgB subunit CAETHG_2472, CAETHG_2853 CUU_c07600, CUU_cO4O9O CLRAG_26960 2375 EmrB/QacA subfamily drug resistance transporter CAETHG_2505 CUU_c04370 CLRAG_37700 2376 Drug/metabolite transporter (DMT) superfamily permease CAETHG_2728 CUU_c06330 CLRAG_30500 2377 bacitracin transport system, permease protein CAETHG_2743 CUU_c06470 CLRAG_30430 2378 Uncharacterized membrane-bound YitT protein containing DUF161 and DUF2179 domains CAETHG_2855 CUU_c07620 CLRAG_25190

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2379 transposase CAETHG_3076 CUU_c09830, CUU_c05390 CLRAG_16750 2380 InsO transposase and its inactivated derivatives CAETHG_4055 CUU_cl9200 CLRAG_37620 2381 tRNA modification GTPase CAETHG_2118 CUU_c42920 CLRAG_25730 2382 tRNA(11e)-lysidine synthase CAETHG_1989 CLJU_c41550 CLRAG_04680 2383 twitch protein Pi IT CAETHG_3309 CUU_cl2270 CLRAG_11530 2384 Protein containing Y_Y_Y domain CAETHG_1563 CUU_c37020 CLRAG_36560 2385 Histidine signaling kinase CAETHG_1843 CUU_c39970 CLRAG_22210 2386 Histidine signaling kinase CAETHG_3499 CUU_cl4180 CLRAG_09510 2387 Histidine signaling kinase CAETHG_3690, CAETHG_3845 CUU_cl5810, CUU_cl7320 CLRAG_29260 2388 Histidine signaling kinase CAETHG_0787 CUU_c27040 CLRAG_08800 2389 Histidine signaling kinase CAETHG_2746 CUU_c06500 CLRAG_30400 2390 hypothetical protein CAETHG_2864 CLJU_cO771O CLRAG_25250 2391 DNA-binding response regulator of the OmpR family, contains a REC and a winged helix domain (wHTH) CAETHG_0022 CUU_cl9450 CLRAG_39660 2392 response regulator YcbB two-component system CAETHG_0162 CLJU_c20770 CLRAG_19230 2393 DNA-binding response regulator of the OmpR family, contains a REC and a winged helix domain (wHTH) CAETHG_0357, CAETHG_3011 CUU_c09170, CUU_c22950 CLRAG_01840 2394 DNA-binding response regulator of the OmpR family, contains a REC and a winged helix domain (wHTH) CAETHG_0578 CUU_c25100 CLRAG_17670 2395 DNA-binding response regulator of the OmpR family, contains a REC and a winged helix domain (wHTH) CAETHG_0641 CUU_c25720 CLRAG_03920 2396 DNA-binding response regulator of the OmpR family, contains a REC and a winged helix domain (wHTH) CAETHG_1067 CUU_c30630 CLRAG_16060 2397 arginine utilization regulatory protein CAETHG_1186 CUU_c32880 CLRAG_15450 2398 two-component system of the OmpR family, KdpE response regulator of the KDP operon CAETHG_1796 CUU_c39510 CLRAG_21710 2399 DNA-binding response regulator of the OmpR family, contains a REC and a winged helix domain (wHTH) CAETHG_1844 CUU_c39980 CLRAG_22220 2400 DNA-binding response regulator of the OmpR family, contains a REC and a winged helix domain (wHTH) CAETHG_1873, CAETHG_2978 CUU_c40270, CUU_c08830 CLRAG_07660 2401 DNA-binding response regulator of the OmpR family, contains a REC and a winged helix domain (wHTH) CAETHG_2516 CUU_c04440 CLRAG_37800 2402 DNA-binding response regulator of the OmpR family, contains a REC and a winged helix domain (wHTH) CAETHG_2875 CUU_c07820 CLRAG_25280 2403 DNA-binding response regulator of the OmpR family, contains a REC and a winged helix domain (wHTH) CAETHG_3601 CUU_cl4970 CLRAG_24380 2404 DNA-binding response regulator of the OmpR family, contains a REC and a winged helix domain (wHTH) CAETHG_3689, CAETHG_3844 CUU_cl5800, CUU_cl7310 CLRAG_29270 2405 DNA-binding response regulator of the NarL/FixJ family, contains REC and HTH domains CAETHG_4017 CUU_cl8850 CLRAG_40150 2406 Histidine signaling kinase CAETHG_0358 CUU_c22960 CLRAG_01820 2407 Histidine signaling kinase CAETHG_0636 CUU_c25670 CLRAG_03870 2408 Histidine signaling kinase CAETHG_0645 CUU_c25760 CLRAG_03990 2409 SpoOB-type sensor kinase, alpha CAETHG_0844, CUU_cl0870 CLRAG_03760

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helical domain CAETHG_3177 2410 two-component system of the AgrA family, sensor histidine kinase AgrC CAETHG_1426 CUU_c35180 CLRAG_05690 2411 two-component system of the LytT family, sensor kinase CAETHG_1589 CUU_c37330 CLRAG_36770 2412 Histidine signaling kinase CAETHG_2196 CUU_cOO81O CLRAG_19770 2413 Histidine signaling kinase CAETHG_2877 CUU_cO784O CLRAG_25320 2414 Histidine signaling kinase CAETHG_3012 CUU_cO918O CLRAG_13850 2415 Histidine signaling kinase CAETHG_1194 CUU_c32960 CLRAG_15370 2416 ATPase like histidine kinase, DNA gyrase B and HSP90 CAETHG_1814 CUU_c39680 CLRAG_21930 2417 protein C tight adhesion CAETHG_0874 CUU_c28790 CLRAG_34870 2418 protein In tight adhesion CAETHG_0875 CUU_c28800 CLRAG_34880 2419 pili assembly protein CpaF CAETHG_0876 CUU_c28810 CLRAG_34890 2420 leader peptidase (prepilin peptidase) / Nmethyltransferase CAETHG_0885 CUU_c28890 CLRAG_34970 2421 ubiquinone biosynthesis protein CAETHG_2190 CUU_cOO73O CLRAG_19850 2422 hypothetical protein CAETHG_1306 CUU_c34080 CLRAG_14230 2423 uOP-N-acetyl-O-glucosamine dehydrogenase 1.1.1.22 CAETHG_1308 CUU_c34100 CLRAG_14250 2424 N-acetylglucosaminyldiphosphoundecaprenol-acetyl-beta-O-mannosaminyltransferase 2.4.1.187 CAETHG_1299 CUU_c34010 CLRAG_14160 2425 UDP-N-acetylmuramyl tripeptide synthase CAETHG_2720 CLJU_c06200 CLRAG_07480 2426 UDP-61cHAc:undecaprenyl phosphate-61cHAc-1phosphate transferase 2.7.8,- CAETHG_2340 CUU_cO234O CLRAG_27950 2427 Nucleotide binding universal stress protein of the UspA family CAETHG_1201, CAETHG_1622 CUU_c37680, CUU_c33030 CLRAG_15300 2428 DNA polymerase CAETHG_2223 CUU_cO112O CLRAG_30280 2429 uracil permease CAETHG_0422 CUU_c23580 CLRAG_17590 2430 nucleobase symporter-1 of the NCS1 family CAETHG_1497 CUU_c35900 CLRAG_06400 2431 uracil permease CAETHG_3163 CUU_clO73O CLRAG_12610 2432 uroporphyrinogen decarboxylase CAETHG_0192 CUU_c21070 CLRAG_30650 2433 Uroporphyrinogen P1-decarboxylase CAETHG_0141 CUU_c20580 CLRAG_19400 2434 Uroporphyrinogen decarboxylase (URO-D) CAETHG_0151, CAETHG_0155 CLJU_c20680, CUU_c20710 CLRAG_19290 2435 uroporphyrinogen decarboxylase CAETHG_0564, CAETHG_0566 CLJU_c24990, CUU_c24970 CLRAG_17790 2436 uroporphyrinogen decarboxylase CAETHG_1370 CUU_c27560, CUU_c34730 CLRAG_30730 2437 Protein McsA-protein arginine kinase activator CAETHG_1976 CUU_c41350 CLRAG_23540 2438 Vancomycin resistance protein YoaR, contains a peptidoglycan-binding domain and a VanW domain CAETHG_1249, CAETHG_4028 CLJU_cl8940, CUU_c33500 CLRAG_24780 2439 Vancomycin resistance protein YoaR, contains a peptidoglycan-binding domain and a VanW domain CAETHG_1769 CUU_c39250 CLRAG_21460 2440 putative peptidoglycan lipid 11 flippase CAETHG_1310 CUU_c34120 CLRAG_14270 2441 Antiporter H+/CI- C1cA CAETHG_0387 CUU_c23240 CLRAG_01490 2442 auxiliary factor xanthine hydrogenase CAETHG_2768 CUU_cO677O CLRAG_18570 2443 selenium-dependent xanthine dehydrogenase CAETHG_0457 CUU_c23910 CLRAG_17250 2444 CO or xanthine dehydrogenase, FAD-binding subunit CAETHG_0454 CUU_c23880 CLRAG_17280 2445 CO or xanthine dehydrogenase, FAD-binding subunit 1.1.1.204, 1.17.1.4 CAETHG_0991 CUU_c29920 CLRAG_35920

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2446 xanthine phosphoribosyltransferase 2.4.2.22, 2.4.2.8 CAETHG_3614 CUU_cl5120 CLRAG_24220 2447 xanthine permease CAETHG_0450 CUU_c23850 CLRAG_17320 2448 nucleobase symporter-2 of the NCS2 family CAETHG_3615 CUU_cl5130 CLRAG_24210 2449 KT F/dIT F-diphosphohydrolase CAETHG_1546 CUU_c36850 CLRAG_36380 2450 Sugar kinase of the NBD/HSP70 family, may contain an N-terminal HTH domain CAETHG_3936 CUU_cl8290 CLRAG_00330 2451 hypothetical protein CAETHG_2502 CLJU_c04340 CLRAG_37670 2452 DNA helicase RIA restart replication CAETHG_2985 CUU_c08900 CLRAG_07580 2453 Predicted Zn-dependent peptidase CAETHG_3017 CLJU_cO923O CLRAG_13800 2454 ZIP family zinc transporter CAETHG_2333 CUU_c02280 CLRAG_27880 2455 (K,K)-butanediol dehydrogenase / meso- butanediol dehydrogenase/diacetyl reductase 1.1.1.4, 1.1.1.1 CAETHG_0385 CLJU_c23220 CLRAG_01510 2456 hypothetical protein CAETHG_3340 CUU_cl2580 CLRAG_11220 2457 Predicted Zn-dependent peptidase CAETHG_1449 CUU_c35410 CLRAG_05950 2458 Predicted Zn-dependent peptidase CAETHG_3405 CUU_cl3220 CLRAG_10570 2459 Glyoxylase superfamily II beta-lactamase 3.1.2.6 CAETHG_1267 CUU_c33690 CLRAG_24590 2460 Glyoxylase superfamily II beta-lactamase CAETHG_2957 CUU_c08630 CLRAG_07860 2461 hypothetical protein CAETHG_3638 CUU_cl5360 CLRAG_24100 2462 putrescine carbamoyltransferase CAETHG_2082 CUU_c42560 CLRAG_09040 2463 pyrimidine nucleoside phosphorylase 2.4.2.23, 2.4.2.2, 2.4.2.3, 2.4.2.4, 2.4.2.1 CAETHG_3925 CUU_cl8160 CLRAG_00510 2464 pyrroline 5-carboxylate reductase 1.5.1.2 CAETHG_1593 CUU_c37380 CLRAG_36820 2465 pyruvate carboxylase CAETHG_1594 CUU_c37390 CLRAG_36830 2466 formate-C-acetyltransferase 2.3.1.54 CAETHG_0667 CUU_c25980 CLRAG_04120 2467 formate-C-acetyltransferase 2.3.1.54 CAETHG_1829 CUU_c39830 CLRAG_22080 2468 enzyme that activates pyruvate formate lyase 2.3.1.54 CAETHG_0666 CUU_c25970 CLRAG_04110 2469 enzyme that activates pyruvate formate lyase 2.3.1.54 CAETHG_1828 CUU_c39820 CLRAG_22070 2470 pyruvate kinase 2.7.1.40 CAETHG_2441 CUU_c03260 CLRAG_28860 2471 pyruvate phosphate dikinase 2.7.9.1 CAETHG_2909 CUU_c08140 CLRAG_08210 2472 putative enzyme activating pyruvate formate lyase CAETHG_2021 CUU_c41920 CLRAG_05030 2473 pyruvate ferredoxin/flavodoxin oxidoreduct pelvis 1.2.7.1 CAETHG_0928, CAETHG_3029 CLJU_c09340, CUU_c29340 CLRAG_35360 2474 quinin tRNA ribosyltransferase CAETHG_1278 CUU_c33800 CLRAG_24480 2475 quinolinate synthetase CAETHG_0503 CLJU_c24430 CLRAG_25160 2476 biotin synthase 2.8.1.6 CAETHG_0339 CUU_c22770 CLRAG_02020 2477 Recombination protein RecA CAETHG_3411 CUU_cl3280 CLRAG_10510 2478 DNA helicase RIA restart replication CAETHG_3337 CUU_cl2550 CLRAG_11250 2479 diguanylate cyclase domain-containing protein (GGDEF) CAETHG_3590, CAETHG_3682 CLJU_cl5740, CUU_cl4840 CLRAG_20280 2480 3,4-dihydroxy-2-butanone-4-phosphate synthase / GTP cyclohydrolase II 3.5.4.25 CAETHG_0305 CLJU_c22070 CLRAG_31590 2481 riboflavin synthase, alpha chain 2.5.1.9 CAETHG_0306 CUU_c22080 CLRAG_31600 2482 protein component of ribonuclease P CAETHG_2122 CUU_c42960 CLRAG_25770 2483 ribonuclease RN CAETHG_1547 CUU_c36860 CLRAG_36390 2484 class II ribonucleoside diphosphate reductase CAETHG_2775 CUU_c06840 CLRAG_18680 2485 class III ribonucleoside triphosphate reductase, 1.17.4.2 CAETHG_2287 CUU_c01840 CLRAG_27440

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catalytic subunit 2486 hypothetical protein CAETHG_2324 CUU_c02190 CLRAG_27790 2487 membrane protein - ABC ribose transporter CAETHG_2237 CUU_c01280 CLRAG_30140 2488 ribose-5-phosphate isomerase 5.3.1.6 CAETHG_2336 CUU_c02310 CLRAG_27910 2489 ribose transport system, substrate-binding protein CAETHG_2235 CUU_c01260 CLRAG_30160 2490 ribose phosphate pyrophosphokinase 2.7.6.1 CAETHG_2006 CUU_c41770 CLRAG_04900 2491 23S rRNA pseudouridine 2605 synthase 4.2.1.70 CAETHG_0222 CUU_c21360 CLRAG_30920 2492 23S rRNA-pseudouridine1911/1915/1917- synthase CAETHG_2835 CUU_c07430 CLRAG_32260 2493 23S rRNA-pseudouridine1911/1915/1917- synthase 4.2.1.70 CAETHG_3162 CUU_cl0720 CLRAG_12620 2494 ribosomal protein methyltransferase L11 CAETHG_2893 CUU_c08000 CLRAG_08360 2495 large ribosomal subunit protein L19 CAETHG_3375 CUU_cl2930 CLRAG_10870 2496 large ribosomal subunit protein L7A CAETHG_1953 CLJU_c41100 CLRAG_23290 2497 16S rRNA pseudouridine516 synthase 4.2.1.70 CAETHG_1561 CLJU_c37000 CLRAG_36540 2498 ribosome binding factor A CAETHG_3399 CUU_cl3160 CLRAG_10630 2499 Sugar kinase (pentulose or hexulose) 2.7.1.47, 2.7.1.16 CAETHG_2230 CUU_c01220 CLRAG_30200 2500 Ribulose phosphate 3-epimerase 5.1.3.1 CAETHG_3346 CUU_cl2640 CLRAG_11160 2501 RNA polymerase sigma factor 70 ECF subfamilies CAETHG_0987 CUU_c29880 CLRAG_35890 2502 sigma factor specific for sporulation RNA polymerase CAETHG_1293 CUU_c33950 CLRAG_14100 2503 sigma factor specific for sporulation RNA polymerase CAETHG_3308 CUU_cl2260 CLRAG_11540 2504 RNA polymerase, sigma subunit 28, SigD/FliA/WhiG CAETHG_3131 CLJU_cl0410 CLRAG_12960 2505 RNA polymerase, sigma subunit 29, SigE CAETHG_3314 CUU_cl2320 CLRAG_11480 2506 sigma factor specific for sporulation RNA polymerase CAETHG_1964 CUU_c41230 CLRAG_23420 2507 RNA polymerase, sigma subunit 54, RpoN/SigL CAETHG_1762 CUU_c39170 CLRAG_21320 2508 RNA polymerase, sigma subunit 70, RpoD CAETHG_2917 CUU_c08220 CLRAG_08170 2509 RNA polymerase, sigma subunit, RpsG/SigG CAETHG_3315 CUU_cl2330 CLRAG_11470 2510 host factor protein-1 CAETHG_0207 CUU_c21210 CLRAG_30790 2511 RNase HH CAETHG_3378 CUU_cl2960 CLRAG_10840 2512 ribonuclease-3 CAETHG_3364 CUU_cl2830 CLRAG_10980 2513 ribonuclease Z CAETHG_0745 CUU_c26640 CLRAG_08510 2514 MheB protein, which determines the shape of the rod CAETHG_2356, CAETHG_2814 CLJU_cO722O, CUU_c02500 CLRAG_28110 2515 23S rRNA-(uracil1939-C5)-methyltransferase CAETHG_2442 CUU_c03270 CLRAG_28870 2516 5-adenosylmethionine:tRNAribosyltransferase-isomerase CAETHG_1279 CUU_c33810 CLRAG_24470 2517 S-ribosylhomocysteine lyase / protein LuxS synthesis of autoinducer 2 remote interbacterial interactions (AI-2) CAETHG_0412 CUU_c23480 CLRAG_17630 2518 RND family efflux transporter, MFP subunit CAETHG_2507 CUU_c04390 CLRAG_37720 2519 selenocysteine-specific factor elongation CAETHG_2840 CLJU_c07480, CUU_c27700 CLRAG_32210 2520 selenophosphate synthase 2.7.9.3 CAETHG_2838 CLJU_c07460, CUU_c27720 CLRAG_32230 2521 two-component system, touch histidine kinase YcbA CAETHG_0163 CUU_c20780 CLRAG_19220 2522 MinC location-sensing protein CAETHG_2818 CUU_c07260 CLRAG_26580

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septa 2523 serine-O-acetyltransferase 2.3.1.31, 2.3.1.30 CAETHG_1775 CUU_c39300 CLRAG_21S10 2524 glycine hydroxymethyltransferase 2.1.2.1 CAETHG_3241 CUU_cll500 CLRAG_11950 2525 serine/threonine protein kinase CAETHG_3344 CUU_cl2620 CLRAG_11180 2526 seryl tRNA synthetase CAETHG_2137 CUU_c00170 CLRAG_20150 2527 shikimate dehydrogenase 1.1.1.282, 1.1.1.25 CAETHG_0904 CUU_c29120 CLRAG_35120 2528 shikimate kinase 2.7.1.71 CAETHG_0903 CUU_c29110 CLRAG_35110 2529 Predicted kinase CAETHG_3445 CUU_cl3630 CLRAG_10240 2530 Transcription regulator containing a PAS domain, an AAA-type ATPase domain, and a DNA-binding Fis domain CAETHG_0105, CAETHG_0463 CLJU_c20240, CUU_c23970 CLRAG_17190 2531 signal peptidase 1 CAETHG_2696 CUU_c05980 CLRAG_07210 2532 signal peptidase 1 CAETHG_3376 CUU_cl2940 CLRAG_10860 2533 signal recognition particle subunit FFH/SRP54 (srp54) CAETHG_3370 CLJU_cl2880 CLRAG_10920 2534 hybrid signal recognition particle receptor CAETHG_3368 CUU_cl2860 CLRAG_10940 2535 Protein containing a PAS domain with an S box CAETHG_0552, CAETHG_0554 CUU_c24870, CUU_c24850 CLRAG_17930 2536 single chain binding protein CAETHG_2104 CLJU_c42780 CLRAG_25590 2537 single-stranded DNA binding protein CAETHG_3105 CUU_cl0150 CLRAG_13220 2538 sirohydrochlorine cobalt chelatase 4.99.1.3 CAETHG_1H3 CUU_c31850 CLRAG_02480 2539 Small Basic Protein CAETHG_3153 CUU_cl0630 CLRAG_12710 2540 sodium/proton-potassium antiporter GerN of the CPA2 family CAETHG_2991 CUU_c08970 CLRAG_07530 2541 spermidine synthase 2.5.1.16 CAETHG_0820 CLJU_c28200 CLRAG_09150 2542 Regulator of protease activity HfIC of the stomatin/prohibitin superfamily CAETHG_2784 CUU_c06940 CLRAG_18780 2543 two-component system, response regulator, sporulation stage 0 protein A CAETHG_3212 CUU_cll220 CLRAG_12240 2544 anti-sigma B factor antagonist CAETHG_2401 CUU_c02860 CLRAG_28460 2545 stage II sporulation protein D CAETHG_0618 CUU_c25490 CLRAG_03710 2546 N-acetylmuramoyl-E-alanine amidase CAETHG_2413 CUU_c02980 CLRAG_28590 2547 CA spore germination protein CAETHG_1745 CUU_c38970 CLRAG_21150 2548 spore germination protein KB CAETHG_1747 CUU_c38990 CLRAG_21170 2549 KS spore germination protein CAETHG_1746 CUU_c38980 CLRAG_21160 2550 putative sporulation protein YtaF CAETHG_2680 CLJU_cO585O CLRAG_07090 2551 Small ribosomal subunit S12P protein methyltransferase CAETHG_3409 CUU_cl3260 CLRAG_10530 2552 Small ribosomal subunit protein S14P CAETHG_1934 CUU_c40910 CLRAG_23100 2553 Small ribosomal subunit protein S15P CAETHG_3403 CUU_cl3200 CLRAG_10590 2554 small ribosomal subunit protein S16 CAETHG_3371 CUU_cl2890 CLRAG_10910 2555 Small ribosomal subunit protein S17P CAETHG_1938 CUU_c40950 CLRAG_23140 2556 Small ribosomal subunit protein S18P CAETHG_2103 CUU_c42770 CLRAG_25580 2557 small ribosomal subunit protein S20 CAETHG_2883 CUU_c07900 CLRAG_25380 2558 small ribosomal subunit protein S2 CAETHG_3385 CUU_cl3020 CLRAG_10770 2559 putative sigma-54 modulation protein CAETHG_2363 CUU_c02620 CLRAG_28220 2560 small ribosomal subunit protein S9 CAETHG_1913 CUU_c40700 CLRAG_22890 2561 putative transcriptional regulator of the DeoR family, stage III sporulation protein D CAETHG_2355 CUU_c02490 CLRAG_28100 2562 protein A of stage IV sporulation CAETHG_3331 CUU_cl2490 CLRAG_11310

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2563 sporulation stage V protein S CAETHG_3413 CUU_cl3300 CLRAG_10490 2564 Serine protease of the subtilisin family CAETHG_3433 CLJU_cl3490, CUU_cl3560 CLRAG_10300 2565 succinate dehydrogenase/fumarate reductase, flavoprotein subunit 1.3.99.1 CAETHG_0342 CUU_c22800 CLRAG_01990 2566 succinyldiaminopimelate desuccinylase CAETHG_3852 CUU_cl7390 CLRAG_01300 2567 MFS transporter, sugar transporter (SP) family CAETHG_3935 CUU_cl8280 CLRAG_00340 2568 TadE-like protein CAETHG_0881 CUU_c28850 CLRAG_34930 2569 2-hydroxy-3-oxopropion reductase 1.1.1.60 CAETHG_2186 CUU_c28090, CLJU_c00680 CLRAG_19890 2570 thiamine pyrophosphokinase 2.7.6.2 CAETHG_3347 CUU_cl2650 CLRAG_11150 2571 thiamine phosphate diphosphorylase 2.5.1.3 CAETHG_1204 CUU_c33060 CLRAG_15270 2572 thiamine phosphate pyrophosphorylase 2.5.1.3 CAETHG_3428 CUU_cl3440 CLRAG_10350 2573 Predicted thioesterase 3.1.2. CAETHG_1780 CUU_c39350 CLRAG_21560 2574 thioredoxin CAETHG_1893 CLJU_c40500 CLRAG_22690 2575 Thioredoxin reductase (NADPH) 1.6.4.5, 1.8.1.9 CAETHG_1892 CLJU_c40490 CLRAG_22680 2576 threonine dehydratase 4.3.1.19 CAETHG_3611 CUU_cl5090 CLRAG_24280 2577 threonine kinase CAETHG_1111 CUU_c31830 CLRAG_02460 2578 threonine synthase 4.2.3.1, 4.2.99.2 CAETHG_1217 CUU_c33180 CLRAG_15110 2579 threonyl-tRNA synthetase CAETHG_1347 CUU_c34470 CLRAG_14550 2580 dTMP kinase 2.7.4.12, 2.7.4.9 CAETHG_2245 CLJU_cO139O CLRAG_27050 2581 Tetratricopeptide repeat-containing protein CAETHG_1319 CLJU_c34200 CLRAG_14350 2582 Tetratricopeptide repeat-containing protein CAETHG_1525 CUU_c36150 CLRAG_06670 2583 Tetratricopeptide repeat-containing protein CAETHG_1894 CUU_c40510 CLRAG_22700 2584 TPR repeat containing protein CAETHG_1897 CLJU_c40540 CLRAG_22730 2585 fructose-6-phosphate aldolase family TalC/MipB 2.2.1.2 CAETHG_0665 CUU_c25960 CLRAG_04100 2586 transaldolase 2.2.1.2 CAETHG_1810 CUU_c39640 CLRAG_21880 2587 transcription antitermination protein nusG CAETHG_1960 CUU_c41170 CLRAG_23360 2588 Rho transcription termination factor CAETHG_2327 CUU_c02220 CLRAG_27820 2589 transcription-repair coupling factor CAETHG_2001 CUU_c41720 CLRAG_04850 2590 uncharacterized protein CAETHG_2369 CUU_c02680 CLRAG_28280 2591 DNA-binding transcriptional regulator LsrR of the DeoR family CAETHG_0480 CUU_c24220 CLRAG_24900 2592 Blal family transcription regulator, penicillinase repressor CAETHG_0584 CUU_c25160 CLRAG_03500 2593 DNA-binding transcriptional regulator of the MerR family CAETHG_0633 CUU_c25640 CLRAG_03840 2594 Lrp/AsnC family transcriptional regulator, leucine-sensitive regulatory protein CAETHG_0697 CUU_c26210 CLRAG_04290 2595 Regulatory protein of the MerR HTH family CAETHG_0758 CUU_c26770 CLRAG_08640 2596 DNA-binding transcriptional regulator of the PadR family CAETHG_0778 CUU_c26940 CLRAG_08790 2597 protein containing a sigma-54 interaction domain CAETHG_1556 CUU_c36950 CLRAG_36490 2598 redox-sensitive repressor transcriptions CAETHG_1581 CUU_c37250 CLRAG_36690 2599 DNA-binding transcriptional regulator of the LysR family CAETHG_1782 CUU_c39370 CLRAG_21580 2600 Helix-loop-helix domain CAETHG_1862 CUU_c40130 CLRAG_22360

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2601 mRNA interferase MazF CAETHG_2419 CUU_c03040 CLRAG_28650 2602 Lrp/AsnC family transcriptional regulator, leucine-sensitive regulatory protein CAETHG_2477 CUU_c04150 CLRAG_26910 2603 DNA binding protein type AgaC CAETHG_2497 CUU_c04290 CLRAG_26770 2604 DNA-binding response regulator of the OmpR family, contains a REC and a winged helix domain (wHTH) CAETHG_2531, CAETHG_2867 CUU_c04590, CUU_c07750 CLRAG_37950 2605 Transcription regulator, contains the HTH domain of the XRE family CAETHG_3453 CUU_cl3710 CLRAG_10130 2606 Transcription regulator of the ABrB family, T protein of sporulation stage V CAETHG_1999 CUU_c41700 CLRAG_04830 2607 DNA binding protein type AgaC CAETHG_0926 CUU_c29330 CLRAG_35340 2608 AgaC family transcriptional regulator CAETHG_1193 CUU_c32950 CLRAG_15380 2609 AgaC family transcriptional regulator CAETHG_1411 CUU_c35020 CLRAG_26280 2610 DNA binding protein type AgaC CAETHG_3626 CUU_cl5240 CLRAG_24110 2611 ArgR family transcriptional regulator CAETHG_3019, CAETHG_3208 CUU_clll90, CUU_c09250 CLRAG_13780 2612 ArsR family transcription regulator CAETHG_0267 CUU_c21790 CLRAG_31330 2613 ArsR family transcriptional regulator CAETHG_0947 CUU_c29530 CLRAG_35520 2614 DNA-binding transcriptional regulator of the ArsR family CAETHG_2289 CUU_c01860 CLRAG_27460 2615 ArsR family transcriptional regulator CAETHG_3663 CUU_cl5640 CLRAG_32690 2616 Lrp/AsnC family transcriptional regulator, leucine-sensitive regulatory protein CAETHG_0190 CUU_c21050 CLRAG_30630 2617 transcriptional regulator of the BadM/Rrf2 family CAETHG_1298 CUU_c34000 CLRAG_14150 2618 transcriptional regulator of the BadM/Rrf2 family CAETHG_3292 CUU_cl2100 CLRAG_11700 2619 DeoR family transcriptional regulator CAETHG_0144 CUU_c20610 CLRAG_19370 2620 DeoR family transcriptional regulator CAETHG_0677 CUU_c26080 CLRAG_04170 2621 DeoR family transcriptional regulator CAETHG_3685 CUU_cl5770 CLRAG_32930 2622 DNA-binding transcriptional regulator of the MocR family, contains aminotransferase domain 2.6.1.23, 2.6.1.1 CAETHG_0037 CUU_cl9600 CLRAG_39520 2623 DNA-binding transcriptional regulator of the MocR family, contains aminotransferase domain 2.6.1.23, 2.6.1.1 CAETHG_1134 CUU_c32060 CLRAG_02690 2624 DNA-binding transcription regulator YhcF family GntR CAETHG_1908 CUU_c40650 CLRAG_22840 2625 GntR family transcriptional regulator, arabinose operon transcriptional repressor CAETHG_2231 CLJU_cO123O CLRAG_30190 2626 GntR family transcription regulator CAETHG_2767 CUU_c06760 CLRAG_18560 2627 GntR family transcriptional regulator, transcriptional repressor for the pyruvate dehydrogenase complex CAETHG_3474 CUU_cl3910 CLRAG_09220 2628 regulatory protein of the gntR family CAETHG_3915 CUU_cl8060 CLRAG_00590 2629 HxIR family transcriptional regulator CAETHG_0486 CUU_c37760, CUU_c24280 CLRAG_24950 2630 HxIR family transcriptional regulator CAETHG_3884 CUU_cl7760 CLRAG_00950 2631 HxIR family transcriptional regulator CAETHG_0932 CUU_c29380 CLRAG_35380 2632 HxIR family transcriptional regulator CAETHG_2177 CUU_c00590 CLRAG_19990 2633 IcIR family transcriptional regulator CAETHG_3442 CUU_cl3600 CLRAG_10270 2634 Laci family transcription regulator CAETHG_2293 CUU_c01900 CLRAG_27500 2635 DNA-binding transcriptional regulator of the LysR family CAETHG_0059 CUU_cl9790 CLRAG_39340 2636 DNA-binding transcriptional regulator of the LysR family CAETHG_1229 CUU_c33300 CLRAG_14960 2637 LysR family transcriptional regulator CAETHG_1742 CUU_c38940 CLRAG_21120

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2638 LytTR family transcriptional regulator CAETHG_0532 CUU_c24670 CLRAG_18160 2639 LytTR family transcriptional regulator CAETHG_0727 CUU_c26460 CLRAG_04550 2640 DNA-binding transcriptional regulator of the MarR family CAETHG_0345 CUU_c22830 CLRAG_01960 2641 MarR family transcriptional regulator CAETHG_2051 CUU_c42200 CLRAG_05310 2642 DNA-binding transcriptional regulator of the MarR family CAETHG_2541 CUU_c04690 CLRAG_38070 2643 MarR family transcriptional regulator CAETHG_3646 CUU_cl5450 CLRAG_32580 2644 MarR family transcriptional regulator CAETHG_4023 CUU_cl8890 CLRAG_40080 2645 DNA-binding transcriptional regulator of the MerR family CAETHG_3243 CUU_cll520 CLRAG_11930 2646 poly-beta-hydroxybutyrate-sensitive repressor CAETHG_0340 CUU_c22780 CLRAG_02010 2647 DNA-binding transcriptional regulator of the PadR family CAETHG_0551 CUU_c24840 CLRAG_17940 2648 DNA-binding transcriptional regulator of the PadR family CAETHG_0984 CUU_c29850 CLRAG_35860 2649 DNA-binding transcriptional regulator of the PadR family CAETHG_1726 CUU_c38780 CLRAG_21040 2650 DNA-binding transcriptional regulator of the PadR family CAETHG_3698 CUU_cl6040 CLRAG_33010 2651 transcriptional regulator of the RpiR family CAETHG_0221 CUU_c21350 CLRAG_30910 2652 TetR family transcriptional regulator CAETHG_0459 CUU_c23930 CLRAG_17230 2653 TetR family transcriptional regulator CAETHG_0631 CUU_c25620 CLRAG_03820 2654 TetR family transcriptional regulator CAETHG_0936 CUU_c29420 CLRAG_35410 2655 TetR family transcriptional regulator CAETHG_0940 CUU_c29460 CLRAG_35450 2656 TetR family transcriptional regulator CAETHG_1388 CLJU_c34900 CLRAG_26140 2657 TetR family transcriptional regulator CAETHG_1493 CUU_c35860 CLRAG_06360 2658 TetR family transcriptional regulator CAETHG_2189 CLJU_cOO72O CLRAG_19860 2659 TetR family transcriptional regulator CAETHG_2470 CLJU_c04070 CLRAG_29180 2660 TetR family transcriptional regulator CAETHG_3141 CUU_cl0510 CLRAG_12830 2661 TetR family transcriptional regulator CAETHG_3491 CLJU_cl4100 CLRAG_09450 2662 transcriptional regulator of the TraR/DksA family CAETHG_3908 CUU_cl7990 CLRAG_00640 2663 transcription regulator, XRE family with cupin sensor CAETHG_0377 CUU_c23140 CLRAG_01670 2664 transcription regulator, XRE family with cupin sensor CAETHG_3450 CUU_cl3680 CLRAG_10190 2665 glucokinase 2.7.1.11 CAETHG_0166 CUU_c20810 CLRAG_19190 2666 transketolase 2.2.1.1 CAETHG_2420 CUU_c03050 CLRAG_28660 2667 transketolase 2.2.1.1 CAETHG_2421 CUU_c03060 CLRAG_28670 2668 translation elongation factor 2 (EF-2/EF-G) CAETHG_1979 CUU_c41380 CLRAG_23570 2669 elongation factor G CAETHG_1950 CUU_c41070 CLRAG_23260 2670 bacterial translation initiation factor 1 (blF-1) CAETHG_1925 CUU_c40820 CLRAG_23010 2671 NhaC family transporter CAETHG_2983 CLJU_c08880 CLRAG_07600 2672 Na+/H+ antiporter NhaD CAETHG_0728 CLJU_c26470 CLRAG_04560 2673 trigger factor CAETHG_1473 CUU_c35650 CLRAG_06180 2674 triosephosphate isomerase 5.3.1.1 CAETHG_1758 CUU_c39130 CLRAG_21280 2675 triphosphoribosyldephospho-CoA synthase CAETHG_0606 CUU_c25370 CLRAG_03640 2676 tRNA-specific 2-thiouridylase CAETHG_0402 CUU_c23380 CLRAG_01370 2677 tRNA-(guanine-N(7)-)-methyltransferase CAETHG_0964 CUU_c29660 CLRAG_35660 2678 tRNA-(guanine37-N1)-methyltransferase CAETHG_3374 CUU_cl2920 CLRAG_10880 2679 23S rRNA (uracil-5-)-methyltransferase RumA CAETHG_2969 CUU_c08750 CLRAG_07740

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2680 tRNA dimethylallyltransferase CAETHG_0208 CLJU_c21220 CLRAG_30800 2681 poly(A) polymerase CAETHG_2258 CLJU_cO152O CLRAG_27180 2682 tRNA pseudouridine 38-40 synthase 4.2.1.70 CAETHG_1915 CUU_c40720 CLRAG_22910 2683 tRNA pseudouridine55 synthase 4.2.1.70 CAETHG_3401 CUU_cl3180 CLRAG_10610 2684 tRNA-2-methylthio-N6- dimethylallyladenosine synthase CAETHG_0211 CUU_c21250 CLRAG_30830 2685 tRNA (adenine34) deaminase CAETHG_2192 CUU_c00760 CLRAG_19820 2686 tRNA-i20-dihydrouridine synthase CAETHG_1985 CUU_c41510 CLRAG_04640 2687 tRNA-u20a,u20b-dihydrouridine synthase CAETHG_1727 CUU_c38790 CLRAG_21050 2688 Protein of the Tgr operon repressor family CAETHG_1560 CUU_c36990 CLRAG_36530 2689 tryptophan synthase, alpha chain CAETHG_3707 CUU_cl6130 CLRAG_33100 2690 tryptophan synthase, beta chain 4.2.1.20, 4.1.2.8 CAETHG_3706 CUU_cl6120 CLRAG_33090 2691 tryptophanyl-tRNA synthetase CAETHG_1686 CUU_c38290 CLRAG_20760 2692 TspO- and MBR-related proteins CAETHG_0611 CUU_c25420 CLRAG_03700 2693 HAMP domain-containing protein CAETHG_3269 CUU_cll780 CLRAG_11760 2694 two-component transcription regulator of the AgaC family CAETHG_1815 CUU_c39690 CLRAG_21940 2695 two-component transcription regulator of the LuxR family CAETHG_0883 CUU_c28870 CLRAG_34950 2696 two-component transcription regulator of the LytTR family CAETHG_1425 CUU_c35170 CLRAG_05680 2697 two-component transcription regulator of the LytTR family CAETHG_1588 CUU_c37320 CLRAG_36760 2698 two-component transcription regulator of the LytTR family CAETHG_3465 CUU_cl3820 CLRAG_10020 2699 DNA-binding response regulator of the OmpR family, contains a REC and a winged helix domain (wHTH) CAETHG_0041 CUU_cl9640 CLRAG_39500 2700 DNA-binding response regulator of the OmpR family, contains a REC and a winged helix domain (wHTH) CAETHG_1195, CAETHG_3268 CUU_cll770, CUU_c38680, CUU_c32970 CLRAG_15360 2701 DNA-binding response regulator of the OmpR family, contains a REC and a winged helix domain (wHTH) CAETHG_3498, CAETHG_3513 CUU_cl4390, CUU_cl4170 CLRAG_09500 2702 two-component system of the NarL family, sensor histidine kinase DegS CAETHG_0884 CUU_c28880 CLRAG_34960 2703 leader peptidase (prepilin peptidase) / Nmethyltransferase CAETHG_2643 CUU_c05610 CLRAG_06740 2704 Pile type IV pili assembly protein CAETHG_3180 CUU_cl0910 CLRAG_12550 2705 pantothenate kinase type III 2.7.1.33 CAETHG_1986 CUU_c41520 CLRAG_04650 2706 flagellum-specific ATP synthase CAETHG_3115 CUU_cl0250 CLRAG_13120 2707 tyrosyl-tRNA synthetase CAETHG_1677 CUU_c38210 CLRAG_20670 2708 UDP-galactopyranosome mutase 5.4.99.9 CAETHG_1252 CUU_c33530 CLRAG_24750 2709 UDP-glucose-4-epimerase 5.1.3.7, 5.1.3.2 CAETHG_0258 CUU_c21710 CLRAG_31300 2710 UDP-N-acetylglucosamine-1carboxyvinyltransferase 2.5.1.7 CAETHG_2027, CAETHG_2352 CUU_c02460, CUU_c41980 CLRAG_05090 2711 UDP-61cChAc3AcA epimerase 5.1.3.14 CAETHG_1305 CUU_c34070 CLRAG_14220 2712 UDP-|\|-acetylglucosamine-2-epimerase (non-hydrolyzing) 5.1.3.14 CAETHG_2341 CUU_cO235O CLRAG_27960 2713 processive 1,2-diacylglycerol-beta- glucosyltransferase CAETHG_2321 CUU_c02160 CLRAG_27760 2714 UDP-N-acetylglucosamine-Nacetylmuramylpentapeptide-Nacetylglucosaminetransferase 2.4.1.227 CAETHG_3028 CUU_c09330 CLRAG_13770 2715 UDP-N-acetylmuramate dehydrogenase 1.1.1.158 CAETHG_2433 CUU_c03180 CLRAG_28790

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2716 UDP-S-acetylmuramate-E-alanine ligase 6.3.2.8 CAETHG_2010 CUU_c41810 CLRAG_04940 2717 UDP-N-acetylmuramoyltripeptide-O-alanyl-Oalanine ligase 6.3.2.10, 6.3.2.15 CAETHG_3148 CUU_clO58O CLRAG_12760 2718 UDP-S-acetylmuramoylalanine-Oglutamate ligase 6.3.2.9 CAETHG_1980 CUU_c41450 CLRAG_04580 2719 UDP-S-acetylmuramoylalanyl-O-glutamate-2,6diaminopimelate ligase 6.3.2.13 CAETHG_3147 CUU_clO57O CLRAG_12770 2720 undecaprenyl diphosphate synthase CAETHG_1455 CUU_c35470 CLRAG_06000 2721 undecaprenyl diphosphate synthase CAETHG_3389 CUU_cl3060 CLRAG_10730 2722 undecaprenide diphosphatase 3.6.1.27 CAETHG_2722 CUU_c06220 CLRAG_07500 2723 polyprenylglycosylphosphotransferase for exopolysaccharide biosynthesis CAETHG_1300 CUU_c34020 CLRAG_14170 2724 uracilphosphoribosyltransferase 2.4.2.9 CAETHG_2337 CUU_cO232O CLRAG_27920 2725 uridylate kinase 2.7.4.14, 2.7.4.-, 2.7.4.4, 2.7.4.22, 2.7.4.9 CAETHG_3387 CUU_cl3040 CLRAG_10750 2726 urocanate hydratase 4.2.1.49 CAETHG_0234 CUU_c21480 CLRAG_31040 2727 methyltransferase/uroporphyrinogen synthase III 2.1.1.107, 4.2.1.75, 1.3.1.76 CAETHG_1125 CUU_c31970 CLRAG_02600 2728 UTP-glucose-1-phosphate uridylyltransferase 2.7.7.9 CAETHG_1318, CAETHG_2523 CLJU_c04510, CUU_c34190 CLRAG_14340 2729 valyl-tRNA synthetase CAETHG_1366 CUU_c34690 CLRAG_14770 2730 Glycopeptide antibiotic resistance protein CAETHG_3170 CUU_clO8OO CLRAG_22450 2731 putative peptidoglycan lipid 11 flippase CAETHG_1302 CLJU_c34040 CLRAG_14190 2732 Xaa-Pro-dipeptidase CAETHG_0961 CLJU_c29640 CLRAG_35630 2733 Xaa-Pro-aminopeptidase 3.4.11.1, 3.4.11.2, 3.4.13.3, 3.4.11.23 CAETHG_3189 CUU_cll000 CLRAG_12460 2734 CO- or xanthine dehydrogenase, Mo-binding subunit 1.1.1.204, 1.17.1.4 CAETHG_0993 CUU_c29940 CLRAG_35940 2735 xanthine dehydrogenase, apoprotein molybdenum-binding subunit 1.1.1.204, 1.17.1.4 CAETHG_0423 CUU_c23590 CLRAG_17580 2736 CO or xanthine dehydrogenase, Mo binding subunit CAETHG_0456 CUU_c23900 CLRAG_17260 2737 xylulokinase 2.7.1.17 CAETHG_3933 CUU_cl8250 CLRAG_00350 2738 phospholipase C CAETHG_0300 CUU_c22020 CLRAG_31550 2739 Threonine dehydrogenase 4.2.1.20, 4.1.2.8 CAETHG_0553 CUU_c24860 CLRAG_17920 2740 Fe-S-cluster-containing component dehydrogenases CAETHG_0614 CUU_c25450 * 2741 1,4-dihydroxy-2-naphthoateprenyltransferase 2.5.1,- CAETHG_1874 CUU_c40280 * 2742 2-deoxy-O-gluconate-3-dehydrogenase CAETHG_0654 CUU_c25850 * 2743 * CUU_c40790 CLRAG_22980 2744 6-phosphogluconate dehydrogenase 1.1.1.44 CAETHG_3250 CUU_cll590 * 2745 6-pyruvoyltetrahydropterin/6carboxytetrahydropterin synthase CAETHG_2465 CUU_c04020 * 2746 ABC-2 type transport system, ATP-binding protein CAETHG_0770 CUU_c26860 * 2747 AL-like protein CAETHG_1172 CUU_c32420 * 2748 aconitase 4.2.1.3, 4.2.1.4 CAETHG_1051, CAETHG_2752 CLJU_c30460, CUU_cO662O * 2749 Amino acid transporter CAETHG_2075 CUU_c42500 *

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2750 aldose-1-epimerase 5.1.3.3 CAETHG_3934 CUU_cl8270 * 2751 allantoinase 3.5.2.5 CAETHG_3635 CUU_cl5330 * 2752 amino acid transport system, putative ATP-binding protein CAETHG_0889 CLJU_c27640, CUU_c28940 * 2753 amino acid transport system, putative substrate-binding protein CAETHG_0891 CUU_c28960 * 2754 anaerobic sulfite reductase, subunit A 1.8.7.1 CAETHG_0616 CUU_c25470 * 2755 anaerobic sulfite reductase, subunit B 1.8.7.1 CAETHG_0617 CUU_c25480 * 2756 arginine deiminase 3.5.3.6 CAETHG_3021 CUU_c09270 * 2757 arginine antiporter:ornithine / lysine permease CAETHG_3024 CLJU_cO929O, CUU_c27990 * 2758 aspartate carbamoyltransferase, catalytic subunit 2.1.3.2 CAETHG_3631 CUU_cl5290 * 2759 amino acid aminotransferase branched chain 2.6.1.67, 2.6.1.42, 2.6.1.6 CAETHG_2968 CUU_c08740 CLRAG_07750 2760 * CLJU_c23570, CUU_c28000 CLRAG_17600 2761 carbamate kinase 2.7.2.2 CAETHG_0421, CAETHG_3632 CUU_cl5300 * 2762 carbon storage regulator, CsrA CAETHG_3049 CUU_c09540 * 2763 4-carboxymuconolactone decarboxylase 4.1.1.44 CAETHG_1512 CUU_c36030 * 2764 [citrate(pro-35)-lyase]-ligase CAETHG_0604 CUU_c25350 * 2765 citrate lyase, gamma subunit (acyl group carrier protein) 2.3.3.1 CAETHG_0603, CAETHG_1054 CLJU_c30490, CUU_c25340 * 2766 citrate lyase, alpha subunit/citrate CoAtransferase 2.3.3.1 CAETHG_0601, CAETHG_1052 CLJU_c30470, CUU_c25320 * 2767 citrate lyase, beta subunit/citril CoAlyase 2.3.3.1 CAETHG_0602, CAETHG_1053 CLJU_c30480, CUU_c25330 * 2768 D-3-phosphoglycerate dehydrogenase 1.1.1.95 CAETHG_3249 CUU_cll580 * 2769 deoxyribonucleoside regulator CAETHG_3920 CUU_cl8110 * 2770 allantoinase 3.5.2.5 CAETHG_3636 CUU_cl5340 * 2771 electron transport flavoprotein, apoprotein alpha subunit CAETHG_1868 CLJU_c40220 * 2772 electron transport flavoprotein, beta subunit CAETHG_1869 CUU_c40230 * 2773 2,4-dienoyl-CoA reductase CAETHG_0869 CUU_c28740 CLRAG_34820 2774 2,4-dienoyl-CoA reductase CAETHG_3711 CUU_cl6160, CUU_c38590 * 2775 ethanolamine utilization protein EutN CAETHG_1824, CAETHG_3284 CLJU_c39780, CUU_cll930 CLRAG_22030 2776 nitrogen fixation protein NifB CAETHG_0418 CUU_c23540 * 2777 Fur family transcriptional regulator, ferric iron uptake regulator CAETHG_0018 CUU_cl9410 * 2778 ferredoxin-like protein CAETHG_1866 CLJU_c40200 * 2779 flagellin CAETHG_3058 CUU_c09630 * 2780 diguanylate cyclase domain-containing protein (GGDEF) CAETHG_2464 CLJU_c04010 * 2781 gluconokinase 2.7.1.12 CAETHG_3252 CUU_cll610 * 2782 high-affinity gluconate transporter of the Gnt-I system CAETHG_0816 CUU_c28160 * 2783 * CLJU_c28110, CUU_c38380 CLRAG_09070 2784 glycerol 2-dehydrogenase (NAD+) 1.1.1.6 CAETHG_0738 CUU_c26570 * 2785 glycerol dehydratase, cobalamin-independent, large subunit 2.3.1.54 CAETHG_3274 CUU_cll830 * 2786 glycerol dehydratase, cobalamin-independent, small subunit 2.3.1.54 CAETHG_3275 CUU_cll840 *

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2787 putative glycosyltransferase, exosortase G associated CAETHG_2463 CUU_cO4OOO * 2788 Putative flippase GtrA (bactoprenol-linked glucose transmembrane translocase) CAETHG_1736 CUU_c38880 * 2789 Protein containing a LysR substrate binding domain CAETHG_0002 CUU_cl9260 * 2790 spore coat protein analogue CAETHG_0029 CUU_cl9520 * 2791 vesicle binding protein CAETHG_0039 CUU_cl9620 * 2792 hypothetical protein CAETHG_0082 CUU_c20020 CLRAG_32500 2793 Adenylate transferase biosynthesis molybdopterin or thiamine CAETHG_0087, CAETHG_0104 CUU_c20230, CUU_c20060 CLRAG_29690 2794 hypothetical protein CAETHG_0199 CUU_c21130 * 2795 protein of unknown function (DUF4830) CAETHG_0202 CUU_c21160 * 2796 hypothetical protein CAETHG_0203 CUU_c21170 * 2797 hypothetical protein CAETHG_0212 CUU_c21260 * 2798 hypothetical protein CAETHG_0214 CUU_c21280 * 2799 Protein of unknown function (DUF1177) CAETHG_0281 CUU_c27890 * 2800 hypothetical protein CAETHG_0295 CUU_c21970 * 2801 protein of unknown function (DUF4430) CAETHG_0328 CUU_c22270, CUU_c22290 CLRAG_31880 2802 Predicted TIM-barrel domain-containing enzyme CAETHG_0362 CUU_c23000 * 2803 GntR family transcription regulator/MocR family aminotransferase CAETHG_0400 CUU_c23360 * 2804 GntR family transcription regulator/MocR family aminotransferase CAETHG_0401 CUU_c23370 * 2805 hypothetical protein 3.1.4.2, 3.1.4.46 CAETHG_0414 CUU_c23500 * 2806 hypothetical protein CAETHG_0479 CUU_c24210 * 2807 protein of unknown function (DUF4111) CAETHG_0521 CUU_c24580 * 2808 DNA polymerase beta domain region CAETHG_0522 CUU_c24590 * 2809 predicted nucleotidyl transferase UPF0157 family containing the GrpB domain CAETHG_0526 CUU_c24620 CLRAG_30000 2810 hypothetical protein CAETHG_0623 CLJU_c30950, CUU_c27570, CUU_c25540 * 2811 Protein of the Sdpl/YhfL family CAETHG_0627, CAETHG_3804 CUU_c25580, CUU_cl6940 * 2812 Quinol monooxygenase YgiN CAETHG_0629 CLJU_c25600 * 2813 CDP-diacylglycerol glycerol-3-phosphate-3phosphatidyltransferase CAETHG_0642 CUU_c25730 CLRAG_03930 2814 hypothetical protein CAETHG_0668 CUU_c25990 * 2815 Uncharacterized conserved protein (DUF2149) CAETHG_0669 CUU_c26000 * 2816 ExbB/TolQ biopolymer transport protein CAETHG_0670 CUU_c26010 * 2817 Fibronectin type III domain-containing protein CAETHG_0672 CUU_c26030 * 2818 hypothetical protein CAETHG_0679 CUU_c26100 * 2819 Phosphodiesterase type 1 / nucleotide pyrophosphatase CAETHG_0711 CUU_c26310 * 2820 hypothetical protein CAETHG_0722 CUU_c26410 * 2821 ABC-2 family transport protein CAETHG_0769 CUU_c26850 * 2822 Uncharacterized membrane protein CAETHG_0772 CUU_c26880 * 2823 protein of unknown function (DUF2935) CAETHG_0782 CUU_c26980 * 2824 hypothetical protein CAETHG_0783 CUU_c26990 *

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2825 hypothetical protein CAETHG_0807 CUU_c27220 * 2826 Acetylesterase/lipase CAETHG_0864 CUU_c28690 CLRAG_34770 2827 hypothetical protein CAETHG_0935 CUU_c29410 * 2828 Protein of unknown function (DUF2680) CAETHG_0955 CUU_c29590 CLRAG_35580 2829 Protein containing a short C-terminal domain CAETHG_0958 CUU_c29620 CLRAG_35610 2830 Protein containing a 4Pe-4B-binding domain CAETHG_0959 CUU_c29630 CLRAG_35620 2831 uroporphyrinogen decarboxylase CAETHG_1046 CUU_c30410 * 2832 Heme degrading protein CAETHG_1071 CUU_c30670 * 2833 hypothetical protein CAETHG_1089 CUU_c30890 CLRAG_16270 2834 protein of unknown function (DUF4829) CAETHG_1090 CUU_c30900 CLRAG_16280 2835 hypothetical protein CAETHG_1092 CUU_c30920 CLRAG_16300 2836 protein of unknown function (DUF4829) CAETHG_1098 CLJU_c30930 CLRAG_16310 2837 hypothetical protein CAETHG_1103 CUU_c31050 * 2838 hypothetical protein CAETHG_1155 CUU_c32270 CLRAG_23940 2839 Protein containing the N-terminal TfoX domain CAETHG_1161 CUU_c32310 CLRAG_08870 2840 hypothetical protein CAETHG_1165, CAETHG_1658 CUU_c32350 CLRAG_37640 2841 Abi-like protein CAETHG_1171 CUU_c32410 * 2842 epoxyqueuosine reductase CAETHG_1173 CUU_c32750 * 2843 hypothetical protein CAETHG_1178 CUU_c32800 * 2844 hypothetical protein CAETHG_1326 CUU_c34270 * 2845 hypothetical protein CAETHG_1327 CUU_c34280 * 2846 hypothetical protein CAETHG_1379 CUU_c34810 * 2847 hypothetical protein CAETHG_1391 CUU_c34930 CLRAG_26170 2848 Protein of unknown function (DUF1648) CAETHG_1410 CUU_c35010 * 2849 DNA transformation protein CAETHG_1419 CUU_c35100 * 2850 Zn-dependent protease (contains SpolVFB) CAETHG_1422 CUU_c35140 CLRAG_26390 2851 hypothetical protein CAETHG_1439 CUU_c35300 * 2852 Protein of unknown function (DUF3892) CAETHG_1523 CUU_c36130 * 2853 hypothetical protein CAETHG_1534 CUU_c36240 * 2854 hypothetical protein CAETHG_1541 CUU_c36330 * 2855 hypothetical protein CAETHG_1542 CLJU_c36340 * 2856 hypothetical protein CAETHG_1544 CUU_c36360 * 2857 protein of unknown function (DUF4878) CAETHG_1708 CUU_c38550 * 2858 Protein of unknown function (DUF2889) CAETHG_1725 CUU_c38770 * 2859 hypothetical protein CAETHG_1739 CUU_c38910 * 2860 hypothetical protein CAETHG_1768 CUU_c39230 * 2861 Dolichyl phosphate mannose protein mannosyltransferase CAETHG_1848 CUU_c40010 * 2862 protein of unknown function (DUF2935) CAETHG_1851 CUU_c40040 * 2863 hypothetical protein CAETHG_1857 CLJU_c40080 * 2864 Calcineurin-like phosphoesterase CAETHG_1865 CUU_c40180 * 2865 YtkA-like protein CAETHG_1878 CLJU_c40320 * 2866 hypothetical protein CAETHG_2080 CUU_c42540 * 2867 hypothetical protein CAETHG_2142 CLJU_cOO25O * 2868 Protein containing an AAA-like domain CAETHG_2161 CUU_c00430 * 2869 hypothetical protein CAETHG_2162 CUU_c00440 *

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2870 hypothetical protein CAETHG_2163 CUU_c00450 * 2871 hypothetical protein CAETHG_2165 CUU_c00460 * 2872 DNA-binding transcriptional regulator containing the XRE family HTH domain CAETHG_2166 CLJU_c00470 CLRAG_33390 2873 Protein of the superfamily of major transporters involved in facilitated diffusion CAETHG_2450 CUU_cO388O * 2874 hypothetical protein CAETHG_2452 CUU_c03900 * 2875 succinyldiaminopimelate desuccinylase CAETHG_2453 CUU_cO391O * 2876 Firmicu-CTERM domain-containing protein CAETHG_2461 CUU_c03980 * 2877 exosortase family protein XrtG CAETHG_2462 CUU_c03990 * 2878 hypothetical protein CAETHG_2466 CUU_c04030 * 2879 protein containing a conserved repeat domain CAETHG_2495 CUU_c04270 * 2880 hypothetical protein CAETHG_2496 CUU_cO428O * 2881 ABC-2 transport system permease protein CAETHG_2580 CUU_c05030 CLRAG_38420 2882 hypothetical protein CAETHG_2582 CUU_c05050 CLRAG_38440 2883 hypothetical protein CAETHG_2669 CUU_c05750 * 2884 hypothetical protein CAETHG_2671 CUU_c05770 * 2885 Protein of unknown function (DUF2442) CAETHG_2685, CAETHG_3454 CUU_cl3720 * 2886 hypothetical protein CAETHG_2694 CUU_c05970 * 2887 hypothetical protein CAETHG_2734 CUU_cO639O * 2888 CoxE-like protein containing a VWA domain CAETHG_2738 CUU_c06420 * 2889 hypothetical protein CAETHG_2739 CUU_c06430 * 2890 hypothetical protein CAETHG_2740 CUU_c06440 * 2891 hypothetical protein CAETHG_2859 CUU_c07660 * 2892 hypothetical protein CAETHG_2860 CUU_c07670 * 2893 ABC-2 transport system permease protein CAETHG_2869 CUU_c07770 * 2894 2-enoate reductase CAETHG_2913 CUU_c08180 * 2895 hypothetical protein CAETHG_2924 CUU_c08290 * 2896 Protein of the P0-(0/E)ChK-nuclease superfamily CAETHG_2925 CUU_c08300 * 2897 hypothetical protein CAETHG_2929 CUU_c08340 * 2898 hypothetical protein CAETHG_2930 CUU_c08350 * 2899 hypothetical protein CAETHG_2931 CUU_c08370 * 2900 Protein containing a methyltransferase domain CAETHG_3060 CUU_c09650 * 2901 Protein of unknown function (DUF2920) CAETHG_3061 CUU_c09660 * 2902 lysine N-methylase CAETHG_3062 CUU_cO967O * 2903 hypothetical protein CAETHG_3063 CUU_c09680 * 2904 Predicted AAA-ATPase CAETHG_3086 CUU_c09950, CUU_c09890 CLRAG_13410 2905 Predicted nucleotidyl transferase CAETHG_3087 CUU_c09960 * 2906 Uncharacterized conserved YutE protein of the UPF0331/DUF86 family CAETHG_3088 CUU_c09970 * 2907 hypothetical protein CAETHG_3436 CUU_cl3520 * 2908 Flavodoxin CAETHG_3504 CUU_cl4220 * 2909 purine catabolism regulatory protein CAETHG_3627 CUU_cl5250 * 2910 (5)-ureidoglycine aminohydrolase CAETHG_3629 CUU_cl5270 * 2911 secretion protein of the HlyD family CAETHG_3649 CUU_cl5480 * 2912 hypothetical protein CAETHG_3716 CUU_cl6220 CLRAG_33130

- 89 044153

2913 hypothetical protein CAETHG_3717 CUU_cl6230 CLRAG_33140 2914 hypothetical protein CAETHG_3729 CUU_cl6350 CLRAG_33160 2915 hypothetical protein CAETHG_3739, CAETHG_3742 CLJU_cl6450, CUU_cl6470 * 2916 hypothetical protein CAETHG_3746 CUU_cl6500 * 2917 hypothetical protein CAETHG_3763 CUU_cl6590 CLRAG_33490 2918 hypothetical protein CAETHG_3805 CUU_cl6950 * 2919 protein of unknown function (DUF3784) CAETHG_3806 CUU_cl6960 * 2920 hypothetical protein CAETHG_3808 CUU_cl6980 * 2921 hypothetical protein CAETHG_3816 CUU_cl7040 * 2922 Uncharacterized membrane protein YcaP family DUF421 CAETHG_3817 CUU_cl7050 * 2923 Uncharacterized SAM-binding YcdF family protein DUF218 CAETHG_3854 CUU_cl7410 * 2924 Protein 5-isoprenylcysteine-Omethyltransferase Stel4 CAETHG_3856 CUU_cl7430 * 2925 chromate transporter CAETHG_3866 CLJU_cl7580 * 2926 1_-2-Aminothiazoline-4-carboxylic acid hydrolase CAETHG_3876 CUU_cl7680 CLRAG_01060 2927 HEPN domain-containing protein CAETHG_3937 CUU_cl8300 * 2928 Arylsulfotransferase (ASST) CAETHG_3941 CUU_cl8340 * 2929 hypothetical protein CAETHG_3945 CUU_cl8380 * 2930 hypothetical protein CAETHG_3960 CUU_cl8530 * 2931 hypothetical protein CAETHG_3961 CUU_cl8540 * 2932 Gpl57 virus CAETHG_3962 CUU_cl8550 * 2933 hypothetical protein CAETHG_3963 CUU_cl8560 * 2934 phage-like protein CAETHG_3979 CUU_cl8650 * 2935 Protein containing a methyltransferase domain CAETHG_4031 CUU_cl8970 * 2936 G5 domain containing protein CAETHG_4035 CLJU_cl9010 * 2937 hypothetical protein CAETHG_4040 CUU_cl9060 * 2938 PLP-dependent enzyme of Cys/Met metabolism 2.5.1.-, 2.5.1.48, 2.5.1.49, 4.2.99.9 CAETHG_4050 CUU_cl9160 * 2939 * CUU_c27480 CLRAG_08940 2940 * CUU_c25630 CLRAG_03830 2941 * CLJU_c36220, CUU_c36370 CLRAG_23960 2942 * CUU_c31600 CLRAG_32430 2943 * CUU_c00980 CLRAG_19600 2944 * CUU_c31810 CLRAG_02440 2945 * CUU_cl4450 CLRAG_09750 2946 * CLJU_c30730 CLRAG_16170 2947 * CLJU_c07810, CUU_c03710 CLRAG_16800 2948 * CUU_c31540 CLRAG_16380 2949 * CUU_c42750 CLRAG_25560 2950 * CUU_c30820 CLRAG_16260 2951 * CUU_c22510 CLRAG_32090 2952 Amidase related to nicotinamidase CAETHG_2912 CUU_c08170 * 2953 keto acid reductoisomerase 1.1.1.86, 1.1.1.169, CAETHG_0122 CUU_c20400, CLJU_c20390 CLRAG_25900

- 90 044153

5.4.99.3 2954 keto acid reductoisomerase 1.1.1.86, 1.1.1.169, 5.4.99.3 CAETHG_3633 CUU_cl5310 * 2955 L-rhamnose isomerase 5.3.1.14 CAETHG_2086 CUU_c42600 * 2956 rhamnulokinase 2.7.1.5 CAETHG_2087 CUU_c42610 * 2957 * CUU_c26820 CLRAG_08700 2958 5- methyltetrahydrofolate homocysteine methyltransferase 2.1.1.13, 2.1.1.14 CAETHG_0145, CAETHG_0153 CUU_c20690, CUU_c20620 CLRAG_19360 2959 methyl acceptor sensor chemotaxis transducer with Cache sensor CAETHG_2073 CUU_c42480 * 2960 methyl acceptor sensor chemotaxis transducer with Cache sensor CAETHG_3026 CUU_c09310 * 2961 methyl acceptor sensor chemotaxis transducer with Cache sensor CAETHG_3492 CUU_cl4110 * 2962 * CUU_c29230 CLRAG_35230 2963 methyl acceptor chemotaxis protein CAETHG_1214 CUU_c33150 CLRAG_15140 2964 methyl acceptor sensor chemotaxis transducer with TagH sensor / methyl-acceptor sensor chemotaxis transducer with Cache sensor CAETHG_3981 CUU_cl8670 * 2965 molybdopterinmolybdochelatase CAETHG_0098 CUU_c20170 CLRAG_29750 2966 molybdopterinmolybdochelatase CAETHG_0099 CUU_c20180 CLRAG_29740 2967 N-acyl-O-amino acid deacylase CAETHG_0995 CUU_c29960 CLRAG_35960 2968 allantoate deiminase CAETHG_3630 CUU_cl5280 * 2969 malate dehydrogenase (oxaloacetate- decarboxylating) CAETHG_0605, CAETHG_1055 CUU_c30500, CUU_c25360 * 2970 sulfonate transport system, substrate binding protein CAETHG_394O CUU_cl8330 * 2971 nitrogenase, molybdenum-iron-containing protein, alpha chain CAETHG_0416 CUU_c23520 * 2972 nitrogenase, molybdenum-iron protein, beta chain CAETHG_0415 CUU_c23510 * 2973 non-heme chloroperoxidase CAETHG_1085 CUU_c30810 * 2974 ornithine carbamoyltransferase 2.1.3.3 CAETHG_3022 CUU_c28010, CUU_c09280 * 2975 Site-specific recombinase XerD CAETHG_2138 CUU_c00210 * 2976 Protein containing a helix-loop-helix domain CAETHG_3751 CUU_cl6550 CLRAG_33360 2977 Phosphoglycerate dehydrogenase 1.1.1.95 CAETHG_1012 CUU_c30120 * 2978 prephenate dehydratase 4.2.1.91, 4.2.1.51 CAETHG_0619 CUU_c25500 * 2979 Propanediol utilization protein CAETHG_1818, CAETHG_3288 CUU_c39720, CUU_cll970 CLRAG_21970 2980 iron complex transport system, substrate-binding protein CAETHG_3824, CAETHG_3830 CUU_cl7120, CUU_cl7180 * 2981 tungstate transport system, ATP-binding protein CAETHG_0097 CUU_c20160 CLRAG_29760 2982 spermidine/putrescine transport system, putative ATP-binding protein CAETHG_0707 CUU_c26270 * 2983 ABC-2 type transport system, ATP-binding protein CAETHG_2581 CUU_c05040 CLRAG_38430 2984 ABC-type lipoprotein export system, ATPase component CAETHG_3835 CUU_cl7220 * 2985 tungstate transport system, substrate binding protein CAETHG_0095 CUU_c20140 CLRAG_29780 2986 D-methionine transport system, substrate binding protein CAETHG_2726 CUU_c06300 *

- 91 044153

2987 tungstate transport system, permease protein CAETHG_0096 CUU_c20150 CLRAG_29770 2988 spermidine/putrescine transport system, putative permease protein CAETHG_0708 CUU_c26280 * 2989 spermidine/putrescine transport system, putative permease protein CAETHG_0709 CUU_c26290 * 2990 D-methionine transport system, permease protein CAETHG_2725 CUU_c06290 * 2991 ABC transport system, putative permease protein CAETHG_3651 CUU_cl5500 * 2992 Protein Ela A CAETHG_0806 CUU_c27210 * 2993 Ribosomal protein acetylase S18 Riml CAETHG_1417 CUU_c35080 CLRAG_26340 2994 Acetyltransferase domain-containing protein (GNAT) CAETHG_1420 CUU_c35110 * 2995 * CLJU_c21000 CLRAG_19020 2996 N-terminal region of acyl-CoA thioether hydrolase/VAAT 3.1.2. CAETHG_0718 CUU_c26370 CLRAG_04450 2997 Imidazolone propionase 3.5.2.3 CAETHG_1002 CUU_c30030 * 2998 hypothetical protein CAETHG_2079 CUU_c42530 * 2999 amido hydrolase 3.5.1.47 CAETHG_2723 CUU_c06270 * 3000 amino acid transport system putative permease protein CAETHG_0890 CUU_c28950 * 3001 N-acyl-O-amino acid deacylase CAETHG_0259 CUU_c21720 * 3002 M28 family peptidase CAETHG_1859 CLJU_c40100 * 3003 Sugar phosphate isomerase/epimerase CAETHG_0792 CUU_c27080 * 3004 holo-ACP synthase CAETHG_0598 CUU_c25290 * 3005 Protein containing an AraC-like ligand-binding domain CAETHG_3438 CUU_cl3540 * 3006 AAA domain-containing protein (dynein-related protein subfamily) CAETHG_2733 CUU_c06380 * 3007 three-component ATP receptor independent solute transporter of the DctP family CAETHG_3255 CUU_cll640 * 3008 Putative cell wall binding protein containing repeat 2 CAETHG_0327, CAETHG_0335 CUU_c22350, CUU_c22280 CLRAG_31870 3009 protein of unknown function (DUF4430) CAETHG_0333 CLJU_c22330 CLRAG_31920 3010 Putative binding protein cell wall CAETHG_1424 CUU_c35160 * ZON Putative cell wall binding protein containing repeat 2 CAETHG_2687 CUU_c05900 * 3012 Putative cell wall binding protein containing repeat 2 CAETHG_3812 CLJU_cl7000 * 3013 methyl acceptor chemotaxis protein CAETHG_1045 CLJU_c30400 * 3014 Methyl-acceptor chemotaxis protein (MCP) containing a signaling domain CAETHG_3863 CUU_cl7500 * 3015 chromate transporter CAETHG_1527 CLJU_c36170 CLRAG_24010 3016 malate:Na+-symporter 2.3.3.1 CAETHG_1701, CAETHG_2480 CUU_c38450 * 3017 Methanogenic corrinoid protein MtbCl CAETHG_2844, CAETHG_2849 CLJU_cO756O, CUU_c07510 * 3018 GTPase of the G3E family CAETHG_4042 CUU_cl9080 * 3019 transport system of the coupling factor of energy metabolism, ATP- binding protein CAETHG_0330 CUU_c22310 CLRAG_31900 3020 energy metabolism coupling factor transport system, permease protein CAETHG_0332 CLJU_c22320 CLRAG_31910 3021 nucleoside transport protein CAETHG_3923 CUU_cl8140 *

- 92 044153

3022 D-3-phosphoglycerate dehydrogenase 1.1.1.95 CAETHG_2448 CUU_c03860 * 3023 D-3-phosphoglycerate dehydrogenase 1.1.1.95 CAETHG_3253 CUU_cll620 * 3024 putative hydrolase of selenium metabolism 3.5.1.14, 3.5.1.16 CAETHG_0994 CUU_c29950 CLRAG_35950 3025 curing death protein CAETHG_1097 CUU_c32640 CLRAG_29380 3026 MutS domain V CAETHG_0794 CUU_c27090 * 3027 regulatory protein blaRl CAETHG_2770 CUU_c06790 CLRAG_18590 3028 Acetylesterase/lipase CAETHG_0863 CUU_c28680 CLRAG_34760 3029 hypothetical protein CAETHG_1331 CUU_c34310 * 3030 Enterochelinesterase CAETHG_1418 CUU_c35090 CLRAG_26350 3031 * CUU_c37370 CLRAG_36810 3032 * CUU_c29650 CLRAG_35640 3033 Cobalamin adenosyltransferase for ethanolamine utilization CAETHG_1827, CAETHG_3281 CUU_c39810, CUU_cll900 CLRAG_22060 3034 spermidine/putrescine transport system, putative substrate-binding protein CAETHG_0710 CUU_c26300 * 3035 electron transport flavoprotein quinone oxidoreductase CAETHG_1867 CUU_c40210 * 3036 * CUU_c00150 CLRAG_20170 3037 hypothetical protein CAETHG_0780 CUU_c26960 * 3038 protein containing the SAM radical and an additional 4Pe45-binding domain SPASM CAETHG_1535 CUU_c36250 * 3039 ABC-type Fe3+ transport system, substrate-binding protein CAETHG_3829 CUU_cl7170 * 3040 An uncharacterized protein containing 2Fe-2 and 4Fe-45 clusters and a DUF4445 domain CAETHG_4047 CUU_cl9130 * 3041 Flagellar hook associated protein 3 FlgL CAETHG_3047 CUU_c09520 * 3042 chemotaxis protein MotA CAETHG_0049 CUU_cl9720 CLRAG_39420 3043 chemotaxis protein MotB CAETHG_0048 CUU_cl9710 CLRAG_39430 3044 * CUU_c09550 CLRAG_13560 3045 * CUU_c37490 CLRAG_36900 3046 Ribosomal protein acetylase S18 Riml CAETHG_2992 CUU_c08980 * 3047 diguanylate cyclase domain-containing protein (GGDEF) CAETHG_0173 CUU_c20880 * 3048 * CUU_c28080 CLRAG_08980 3049 Glycosyltransferase involved in cell wall bisynthesis CAETHG_2774 CUU_c06830 * 3050 Dolichyl phosphate mannose protein mannosyltransferase CAETHG_1738 CUU_c38900 * 3051 dolichol phosphate mannosyltransferase CAETHG_2458 CUU_c03960 * 3052 Tetratricopeptide repeat-containing protein CAETHG_3059 CUU_c09640 * 3053 hypothetical protein CAETHG_3085 CLJU_c09940 * 3054 Glycosyltransferase involved in cell wall bisynthesis CAETHG_4033 CUU_cl8990 * 3055 hypothetical protein CAETHG_0379 CUU_c23160 * 3056 Putative flippase GtrA (bactoprenol-linked glucose transmembrane translocase) CAETHG_2067 CUU_c42420 * 3057 Sulfite Exporter TauE/SafE CAETHG_1870 CLJU_c40240 * 3058 putative ATPase CAETHG_3291 CLJU_cl2000 * 3059 Phage integrase family protein CAETHG_0767, CAETHG_3579 CUU_cl4790, CUU_c26830 CLRAG_08710

- 93 044153

3060 iron complex transport system, ATP-binding protein CAETHG_0088 CLJU_c20070 CLRAG_29590 3061 iron complex transport system, permease protein CAETHG_0089 CUU_c20080 CLRAG_29600 3062 Polyferredoxin CAETHG_1879 CLJU_c40330 * 3063 iron complex transport system, substrate-binding protein CAETHG_0090 CLJU_c20090 CLRAG_29660 3064 Protein 5-isoprenylcysteine-Omethyltransferase Stel4 CAETHG_2175 CLJU_cOO57O * 3065 L-rhamnose mutarotase CAETHG_2083 CUU_c42570 * 3066 DNA-binding transcriptional regulator of the LysR family CAETHG_3712 CUU_cl6170 * 3067 hypothetical protein CAETHG_0517 CUU_c24550 * 3068 Transmembrane secretion effector CAETHG_0518 CUU_c24560 * 3069 protein that promotes the absorption of glycerol CAETHG_3280 CUU_cll890 * 3070 DNA-binding transcriptional regulator of the MarR family CAETHG_1175 CUU_c32770 * 3071 DNA-binding transcriptional regulator of the MarR family CAETHG_1209 CUU_c33110 CLRAG_15220 3072 DNA-binding transcriptional regulator of the MarR family CAETHG_3855 CUU_cl7420 * 3073 Zn-dependent protease (contains SpolVFB) CAETHG_0038 CUU_cl9610 * 3074 energy metabolism coupling factor transport system, substrate-specific component CAETHG_0329 CLJU_c22300 CLRAG_31890 3075 Calcineurin-like phosphoesterase CAETHG_3505 CUU_cl4230 * 3076 methyl acceptor chemotaxis protein CAETHG_3913 CUU_cl8040 * 3077 C-methylase for ubiquinone/menaquinone biosynthesis UbiE CAETHG_0499 CUU_c24390 * 3078 * CUU_c22620 CLRAG_32180 3079 * CUU_c24100 CLRAG_30580 3080 Sugar phosphate permease CAETHG_0865 CUU_c28700 CLRAG_34780 3081 Predicted MFS family arabinose efflux permease CAETHG_0866 CUU_c28710 CLRAG_34790 3082 magnesium transporter CAETHG_3007 CLJU_cO913O * 3083 This sulfur transport protein (thiamine biosynthesis) CAETHG_0086, CAETHG_0103 CLJU_c20220, CUU_c20050 CLRAG_34300 3084 molybdate transport system, substrate-binding protein CAETHG_0671 CUU_c26020 * 3085 Protein containing Fe4S4 domain molybdopterin oxido reductase 1.7.7.2 CAETHG_0613 CUU_c25440 * 3086 protein containing molybdenum pterin binding domain CAETHG_0001 CUU_cl9250 * 3087 * CUU_cl9740 CLRAG_39400 3088 putative MATE family efflux protein CAETHG_1208 CUU_c33100 CLRAG_15230 3089 putative MATE family efflux protein CAETHG_0796 CUU_c27110 * 3090 * CUU_c22520 CLRAG_32100 3091 * CUU_c22710 CLRAG_02070 3092 2,4-dienoyl-CoA reductase CAETHG_0867 CUU_c28720 CLRAG_34800 3093 nitroreductase CAETHG_3628 CUU_cl5260 * 3094 N|2+-binding GTPase involved in the regulation of expression and maturation of urease and hydrogenase CAETHG_3834 CUU_cl7210 * 3095 sulfonate transport system, ATP-binding protein CAETHG_3939 CUU_cl8320 *

- 94 044153

3096 sulfonate transport system, permease protein CAETHG_3938 CUU_cl8310 * 3097 * CUU_c08790 CLRAG_07700 3098 nucleobase symporter-1 of the NCS1 family CAETHG_3634 CUU_cl5320 * 3099 nucleobase symporter-1 of the NCS1 family CAETHG_3637 CUU_cl5350 * 3100 Predicted nucleotidyl transferase CAETHG_3082 CUU_c09910 * 3101 HI0074 family nucleotidyl transferase, substrate-binding protein CAETHG_3083 CUU_c09920 * 3102 Uncharacterized OsmC-related protein CAETHG_1871 CUU_c40250 * 3103 hypothetical protein CAETHG_3168 CUU_clO78O * 3104 DNA-binding transcriptional regulator of the PadR family CAETHG_3715 CUU_cl6210 CLRAG_33120 3105 CubicO group peptidase, class C betalactamase family CAETHG_1716 CUU_c38660 * 3106 Transglycosylase CAETHG_3693 CUU_cl5930 * 3107 * CUU_cl5530 CLRAG_32610 3108 * CUU_c22570 CLRAG_32130 3109 * CUU_c22560 CLRAG_32120 3110 * CUU_c22580, CUU_c22540 CLRAG_32140 3111 * CUU_c22600 CLRAG_32160 3112 * CUU_c22590 CLRAG_32150 3113 hypothetical protein CAETHG_0948 CUU_c29540 CLRAG_35530 3114 rarD protein CAETHG_1170 CUU_c32400 * 3115 hypothetical protein CAETHG_2070 CUU_c42450 * 3116 ABC transport system, putative permease protein CAETHG_2871 CUU_c07790 * 3117 MFS DHA1 family transporter, tetracycline resistance protein CAETHG_3495 CUU_cl4140 * 3118 * CUU_c31740 CLRAG_02400 3119 octaprenyl diphosphate synthase 2.5.1.29, 2.5.1.1, 2.5.1.10 CAETHG_1877 CUU_c40310 * 3120 hypothetical protein CAETHG_1875 CUU_c40290 * 3121 serpin B CAETHG_0506 CUU_c24460 * 3122 * CUU_c38400 CLRAG_21860 3123 An uncharacterized protein of the pyridoxamine 5'-phosphate oxidase (PNPOx-) family like) CAETHG_1566 CUU_c37110 * 3124 small redox active disulfide protein 2 CAETHG_0949 CUU_c29550 CLRAG_35540 3125 LuxR family transcriptional regulator, maltose regulon positive regulation protein CAETHG_0007 CUU_cl9300 * 3126 Regulatory protein of the MerR HTH family CAETHG_0781 CUU_c26970 * 3127 DNA-binding transcriptional regulator of the MerR family CAETHG_3503 CUU_cl4210 * 3128 two-component system of the CitB family, response regulator MaIR CAETHG_1703, CAETHG_2485 CUU_c38470 * 3129 * CUU_c27170 CLRAG_20060 3130 response regulator YcbB two-component system CAETHG_2071 CUU_c42460 * 3131 two-component system of the OmpR family, response regulator VanR CAETHG_0296 CUU_c21980, CUU_cl4380 * 3132 RNA polymerase sigma factor 70 CAETHG_1322 CUU_c34230 *

- 95 044153

ECF subfamilies 3133 protein of unknown function (DUF4179) CAETHG_1323 CUU_c34240 * 3134 Protein containing a methyltransferase domain CAETHG_1536 CUU_c36260 CLRAG_23930 3135 two-component system of the CitB family, sensor histidine kinase MalK CAETHG_1704, CAETHG_2484 CUU_c38480 * 3136 Protein containing His kinase A (phosphoacceptor) domain CAETHG_3648 CUU_cl5470 * 3137 Histidine signaling kinase CAETHG_2579 CUU_c05020 CLRAG_38410 3138 Protein containing a PAS domain with an S box CAETHG_0093, CAETHG_0101 CUU_c20120, CUU_c20200 CLRAG_29640 3139 Histidine signaling kinase CAETHG_0957 CUU_c29610 CLRAG_35600 3140 Histidine signaling kinase CAETHG_2872 CUU_c07800 * 3141 spermidine/putrescine transport system, substrate-binding protein CAETHG_0260 CUU_c21730 * 3142 spermidine/putrescine transport system, permease protein CAETHG_0261 CUU_c21740 * 3143 spermidine/putrescine transport system, permease protein CAETHG_0262 CUU_c21750 * 3144 spore coat protein CAETHG_0032 CUU_cl9550 * 3145 spore coat protein analogue CAETHG_0033 CUU_cl9560 * 3146 Coat protein containing F domain CAETHG_0030 CUU_cl9530 * 3147 spore germination protein (permease) amino acids) CAETHG_3655 CUU_cl5600 * 3148 CA spore germination protein CAETHG_2942 CUU_c08490 * 3149 KS spore germination protein CAETHG_2943 CUU_c08500 * 3150 CA spore germination protein CAETHG_3654 CUU_cl5590 * 3151 spore germination protein CAETHG_3656 CUU_cl5610 * 3152 Sugar phosphate isomerase/epimerase CAETHG_0868 CUU_c28730 CLRAG_34810 3153 glycoside/pentoside/hexuronidation simporter of the GPH family CAETHG_0649 CUU_c25800 * 3154 glycoside/pentoside/hexuronidation simporter of the GPH family CAETHG_0655 CUU_c25860 * 3155 transporter of sugars (glycosides-pentosides hexuronides) CAETHG_3437 CUU_cl3530 * 3156 lg-like domain (group 2) CAETHG_0334 CUU_c22340 CLRAG_31930 3157 lg-like domain (group 2) CAETHG_0337 CUU_c22360 CLRAG_32000 3158 Putative intracellular protease/amidase CAETHG_1423 CUU_c35150 * 3159 DNA-binding transcriptional regulator of the MarR family CAETHG_0017 CUU_cl9400 * 3160 Predicted TIM-barrel domain-containing enzyme CAETHG_0365 CLJU_c23020 * 3161 LuxR family transcriptional regulator, maltose regulon positive regulation protein CAETHG_0394 CUU_c23300 * 3162 DNA-binding transcriptional regulator of the MocR family, contains aminotransferase domain CAETHG_0937 CUU_c29430 CLRAG_35420 3163 ArsR family transcription regulator CAETHG_0950, CAETHG_3674 CUU_c29560 CLRAG_35550 3164 DNA-binding transcriptional regulator of the MerR family CAETHG_1513 CUU_c36040 * 3165 DNA-binding transcriptional regulator containing the XRE family HTH domain CAETHG_1707 CUU_c38540 * 3166 DNA-binding transcriptional regulator of the MerR family CAETHG_1858 CLJU_c40090 * 3167 Fis family regulatory protein CAETHG_2076, CUU_c42510, *

- 96 044153

CAETHG_2078 CUU_c42520 3168 DNA-binding response regulator of the OmpR family, contains a REC and a winged helix domain (wHTH) CAETHG_2578 CUU_c05010 CLRAG_38400 3169 FCD domain-containing protein CAETHG_2773 CUU_c06820 CLRAG_18620 3170 Sugar-specific transcriptional regulator TgtB CAETHG_3027 CUU_c09320 * 3171 DNA-binding transcriptional regulator of the MarR family CAETHG_3494 CUU_cl4130 * 3172 DNA-binding transcriptional regulator of the MerR family CAETHG_3594 CUU_cl4880 * 3173 DNA-binding transcriptional regulator of the MarR family CAETHG_3874 CUU_cl7660 CLRAG_01070 3174 GntR family transcription regulator/MocR family aminotransferase 2.6.1.23, 2.6.1.1 CAETHG_3893 CUU_cl7850 * 3175 * CUU_c35940 CLRAG_06440 3176 protein of unknown function (DUF4132) CAETHG_2741 CUU_c06450 * 3177 secretion protein of the HlyD family CAETHG_0323 CUU_c22250 CLRAG_31830 3178 Sugar phosphate permease CAETHG_1781 CUU_c39360 * 3179 Predicted MFS family arabinose efflux permease CAETHG_1839 CUU_c39930 * 3180 SP family MFS transporter, inositol transporter CAETHG_2084 CUU_c42580 * 3181 MFS ACS family transporter, glucarate transporter CAETHG_2449 CUU_c03870 * 3182 ABC transport system, putative permease protein CAETHG_3516 CUU_cl4430 * 3183 * CUU_c22740 CLRAG_02050 3184 ATPase like histidine kinase, DNA gyrase B and HSP90 CAETHG_3514 CUU_cl4400 * 3185 DNA-binding response regulator of the OmpR family, contains a REC and a winged helix domain (wHTH) CAETHG_0956 CUU_c29600 CLRAG_35590 3186 DNA-binding response regulator of the OmpR family, contains a REC and a winged helix domain (wHTH) CAETHG_3647 CUU_cl5460 * 3187 ATPase like histidine kinase, DNA gyrase B and HSP90 CAETHG_3277 CUU_cll860 * 3188 integrase/recombinase XerD CAETHG_3750 CUU_cl6540 CLRAG_33350 3189 demethylmenaquinone methyltransferase/2- methoxy-6-polyprenyl-1,4benzoquinol methylase 2.1.1,- CAETHG_1876 CUU_c40300 * 3190 * CUU_c22750 CLRAG_02040 3191 uroporphyrinogen decarboxylase CAETHG_0197 CUU_c21110 * 3192 Uroporphyrinogen decarboxylase (URO-D) CAETHG_0140 CUU_c20570 * 3193 Vancomycin resistance protein YoaR, contains a peptidoglycan-binding domain and a VanW domain CAETHG_3566 CUU_cl4670 * 3194 aryl alcohol dehydrogenase 1.1.1.1 CAETHG_3710 CLJU_cl6150, CUU_c38580 * 3195 pyridoxal 5'-phosphate synthase, pdxS subunit CAETHG_1804 CUU_c39580 * 3196 5'-phosphate synthase, pdxT subunit CAETHG_1805 CUU_c39590 * 3197 * CUU_c24080 CLRAG_30600 3198 rhamnulose-1-phosphate aldolase 4.1.2.19 CAETHG_2085 CUU_c42590 * 3199 * CUU_c00990 CLRAG_19590 3200 * CUU_c32540 CLRAG_23690 3201 shikimate dehydrogenase 1.1.1.282, CAETHG_0870 CUU_c28750 CLRAG_34830

- 97 044153

1.1.1.25 3202 shikimate kinase CAETHG_1641 CUU_c38140 * 3203 spore germination protein KB CAETHG_2945 CUU_cO851O * 3204 Tat-correcting chaperone TorD CAETHG_0615 CUU_c25460 * 3205 DNA-binding transcriptional regulator of the LysR family CAETHG_0612 CUU_c25430, CUU_c38560 * 3206 DNA-binding transcriptional regulator of the MarR family CAETHG_0797 CUU_c27120 * 3207 DNA-binding transcriptional regulator of the LysR family CAETHG_0872 CUU_c28770 CLRAG_34850 3208 transcription regulator-like protein CAETHG_2927 CUU_cO832O * 3209 DeoR family transcriptional regulator CAETHG_0706 CUU_c26260 * 3210 DeoR family transcriptional regulator CAETHG_2088 CUU_c42620 * 3211 HxIR family transcriptional regulator CAETHG_0717, CAETHG_3595 CLJU_c26360, CUU_cl4890 * 3212 HxIR family transcriptional regulator CAETHG_1567 CUU_c37120 * 3213 HxIR family transcriptional regulator CAETHG_3910 CUU_cl8010 * 3214 transcription regulator of the MarR family with acetyltransferase activity CAETHG_2176 CUU_cOO58O * 3215 DNA-binding transcriptional regulator of the PadR family CAETHG_1325, CAETHG_1333 CLJU_c34330, CUU_c34260 * 3216 * CUU_c35130 CLRAG_26380 3217 transcriptional regulator of the RpiR family CAETHG_3246 CUU_cll550 * 3218 TetR family transcriptional regulator CAETHG_1840 CUU_c39940 * 3219 TetR family transcriptional regulator CAETHG_2851 CUU_cO758O CLRAG_32480 3220 TetR family transcriptional regulator CAETHG_2910 CUU_cO815O * 3221 transketolase 2.2.1.1 CAETHG_0652 CUU_c25830 * 3222 transketolase 2.2.1.1 CAETHG_0651 CUU_c25820 * 3223 L-threonylcarbamoyladenylate synthase CAETHG_0779 CUU_c26950 * 3224 Carrier of di- and tricarboxylates CAETHG_0481 CUU_c24230 * 3225 aldehyde:ferredoxin oxidoreductase 1.2.7.5 CAETHG_0092, CAETHG_0102 CUU_c20110, CLJU_c20210 CLRAG_29650 3226 DNA binding protein type AgaC CAETHG_0656 CUU_c25870 * 3227 Protein containing a helix-loop-helix domain CAETHG_3276 CUU_cll850 * 3228 DNA-binding response regulator of the OmpR family, contains a REC and a winged helix domain (wHTH) CAETHG_0788 CUU_c27050 * 3229 tyrosyl-tRNA synthetase CAETHG_1330 CUU_c34300 * 3230 uroporphyrinogen decarboxylase CAETHG_4044 CUU_cl9100 * 3231 Uroporphyrinogen P1-decarboxylase CAETHG_4043 CUU_cl9090 * 3232 UV damage endonuclease CAETHG_3553 CUU_cl4460 * 3233 xylulokinase 2.7.1.17 CAETHG_3248 CUU_cll570 * 3234 5-(hydroxymethyl)-glutathione dehydrogenase/alcohol dehydrogenase 1.1.1.1 CAETHG_0031 CUU_cl9540 * 3235 (K,K)-butanediol dehydrogenase / meso- butanediol dehydrogenase/diacetyl reductase 1.1.1.1 CAETHG_0650 CUU_c25810 * 3236 (K,K)-butanediol dehydrogenase / meso- butanediol dehydrogenase/diacetyl reductase 1.1.1.4 CAETHG_0653 CUU_c25840 * 3237 E-iditol-2-dehydrogenase CAETHG_3247 CUU_cll560 * 3238 Molybdopterin oxidoreductase 1.7.7.2, 1.2.1.43, 1.1.99.33 CAETHG_0085, CAETHG_2789 * CLRAG_18830 3239 sporulation stage V AD protein CAETHG_0177 * CLRAG_19090

- 98 044153

3240 SpoOE-like regulatory protein sporulation CAETHG_0289 * CLRAG_31470 3241 hypothetical protein CAETHG_0626 * CLRAG_03780 3242 hypothetical protein CAETHG_0703 * CLRAG_04380 3243 hypothetical protein CAETHG_0704 * CLRAG_04390 3244 hypothetical protein CAETHG_0705 * CLRAG_04400 3245 hypothetical protein CAETHG_0927 * CLRAG_35350 3246 hypothetical protein CAETHG_0945 * CLRAG_35500 3247 hypothetical protein CAETHG_1024 * CLRAG_15770 3248 GHKL domain-containing protein CAETHG_1025 * CLRAG_15780 3249 two-component transcription regulator of the LytTR family CAETHG_1026 * CLRAG_15790 3250 hypothetical protein CAETHG_1077, CAETHG_1086 * CLRAG_16250 3251 Protein of unknown function (DUF1064) CAETHG_1093 * CLRAG_32410 3252 hypothetical protein CAETHG_1511 * CLRAG_06530 3253 hypothetical protein CAETHG_1637 * CLRAG_37490 3254 protein of the excisionase family containing a DNA-binding domain CAETHG_1666 * CLRAG_36100 3255 hypothetical protein CAETHG_1668 * CLRAG_36120 3256 putative transcriptional regulator CAETHG_1669 * CLRAG_20580 3257 DNA-binding transcriptional regulator containing the XRE family HTH domain CAETHG_1670 * CLRAG_20590 3258 Site-specific recombinase XerD CAETHG_1671 * CLRAG_20600 3259 hypothetical protein CAETHG_1682 * CLRAG_20720 3260 hypothetical protein CAETHG_1700 * CLRAG_20890 3261 PadR family transcriptional regulator, PadR regulatory protein CAETHG_1722 * CLRAG_20990 3262 Uncharacterized membrane-bound protein CAETHG_1723 * CLRAG_21000 3263 hypothetical protein CAETHG_2061 * CLRAG_05480 3264 transcriptional regulator of the RpiR family CAETHG_2187 * CLRAG_19880 3265 hypothetical protein CAETHG_2338 * CLRAG_27930 3266 Predicted transcriptional regulator containing CBS domains CAETHG_2437 * CLRAG_28830 3267 hypothetical protein CAETHG_2668 * CLRAG_07000 3268 NUDIX domain-containing protein CAETHG_2670 * CLRAG_30010 3269 hypothetical protein CAETHG_2702 * CLRAG_07270 3270 analogue of sporulation stage IV protein CAETHG_2901 * CLRAG_08290 3271 Putative motility protein CAETHG_3094 * CLRAG_13330 3272 hypothetical protein CAETHG_3216 * CLRAG_12200 3273 hypothetical protein CAETHG_3380 * CLRAG_10820 3274 hypothetical protein CAETHG_3458 * CLRAG_10090 3275 Histidine signaling kinase CAETHG_3575 * CLRAG_20390 3276 Two-component response regulator of the SAPR family, consisting of REC, wHTH and BTAD domains CAETHG_3576 * CLRAG_20380 3277 hypothetical protein CAETHG_3967 * CLRAG_00100 3278 protein of unknown function (DUF1540) CAETHG_4060 * CLRAG_39820 3279 * CUU_cO397O * 3280 * CUU_c32730 CLRAG_15600 3281 * CUU_c27620 * 3282 * CUU_c28050 *

- 99 044153

3283 * CUU_c27830, CUU_c27350 * 3284 CAAX protease of autoimmunity CAETHG_2013 CUU_c41840 * 3285 * CUU_c27820, CUU_c27340 * 3286 * CUU_cl4360 * 3287 Predicted amidohydrolase CAETHG_1376 CUU_c34790 * 3288 DNA-3-methyladenine glycosylase 1 CAETHG_1539 CUU_c36310 * 3289 2-iminobutanoate/2-iminopropanoate deaminase CAETHG_1883 CUU_c40370 * 3290 Flagellar hook associated protein 2 CAETHG_3053 CUU_c09580 * 3291 fumarate reductase, flavoprotein subunit CAETHG_1032 CUU_c30250 * 3292 * CUU_c28100 * 3293 * CUU_c27840, CUU_c27360 * 3294 * CUU_c27770, CUU_c27290 * 3295 * CUU_c27780, CUU_c27300 * 3296 * CUU_c27790, CUU_c27310 * 3297 * CUU_c27490 * 3298 * CUU_c27900 * 3299 hypothetical protein CAETHG_0091 CUU_c20100 * 3300 protein of unknown function (DUF4445) CAETHG_0194 CUU_c21090 * 3301 hypothetical protein CAETHG_0784 CUU_c27000 * 3302 Putative ABC transporter type IV CAETHG_0808 CUU_c27230 * 3303 hypothetical protein CAETHG_0810 CUU_c27240 * 3304 hypothetical protein CAETHG_0818 CUU_c28180 * 3305 hypothetical protein CAETHG_1009 CUU_c30100 * 3306 hypothetical protein CAETHG_1010 CUU_c30110 * 3307 PucR protein containing a C-terminal helix-loop-helix domain CAETHG_1028 CUU_c30210 * 3308 Protein of unknown function (DUF1097) CAETHG_1030 CUU_c30230 * 3309 hypothetical protein CAETHG_1036 CUU_c30290 * 3310 Putative binding protein cell wall CAETHG_1038 CUU_c30320 * 3311 hypothetical protein CAETHG_1039 CUU_c30330 * 3312 Microcystin-dependent protein CAETHG_1040 CUU_c30340 * 3313 Acetyltransferase domain-containing protein (GNAT) CAETHG_1041 CUU_c30350 * 3314 hypothetical protein CAETHG_1042 CUU_c30360 * 3315 hypothetical protein CAETHG_1043 CUU_c30370 * 3316 putative transport protein CAETHG_1049 CUU_c30440 * 3317 N-terminal 7TM region of histidine kinase 2.1.1.258 CAETHG_1069 CUU_c30650 * 3318 hypothetical protein CAETHG_1156 CUU_c32280 * 3319 hypothetical protein CAETHG_1159 CUU_c32290 * 3320 protein containing DnaD- and phage-associated domain CAETHG_1160 CUU_c32300 * 3321 hypothetical protein CAETHG_1162 CUU_c32320 * 3322 Putative cincin peptidase CAETHG_1169 CUU_c32390 * 3323 hypothetical protein CAETHG_1328 CUU_c34290 *

- 100 044153

3324 PucR protein containing a C-terminal helix-loop-helix domain CAETHG_1369 CUU_c34720 * 3325 hypothetical protein CAETHG_1377 CUU_c34800 * 3326 hypothetical protein CAETHG_1445 CUU_c35360 * 3327 protein containing aminoacyl-tRNA- editing domain CAETHG_1452 CUU_c35440 * 3328 hypothetical protein CAETHG_1489 CUU_c35810 * 3329 EAL domain-containing protein CAETHG_1490 CUU_c35830 * 3330 EAL domain-containing protein CAETHG_1491 CUU_c35840 * 3331 hypothetical protein CAETHG_1732 CUU_c38840 * 3332 hypothetical protein CAETHG_1850 CLJU_c40030 * 3333 Protein containing a nuclease-related domain CAETHG_1854 CLJU_c40050 * 3334 Uncharacterized membrane protein YeiH CAETHG_1880 CUU_c40340 * 3335 phage regulatory protein of the rha family CAETHG_2141 CLJU_c00240 * 3336 hypothetical protein CAETHG_2143 CUU_c00260 * 3337 hypothetical protein CAETHG_2144 CUU_c00270 * 3338 hypothetical protein CAETHG_2145 CUU_c00280 * 3339 hypothetical protein CAETHG_2146 CLJU_cOO29O * 3340 hypothetical protein CAETHG_2147 CUU_c00300, CUU_c36470 * 3341 hypothetical protein CAETHG_2148 CUU_c00310 * 3342 hypothetical protein CAETHG_2150 CUU_c00330 * 3343 hypothetical protein CAETHG_2151 CLJU_c00340 * 3344 hypothetical protein CAETHG_2153 CUU_c00360 * 3345 hypothetical protein CAETHG_2154 CLJU_cOO37O * 3346 hypothetical protein CAETHG_2156 CUU_c00380 * 3347 hypothetical protein CAETHG_2157 CLJU_cOO39O * 3348 hypothetical protein CAETHG_2159 CLJU_c00410 * 3349 hypothetical protein CAETHG_2160 CLJU_c00420 * 3350 IS605 family transposase OrfB, central region CAETHG_2167 CUU_c00480 * 3351 hypothetical protein CAETHG_2168 CLJU_cOO5OO * 3352 hypothetical protein CAETHG_2169 CUU_c00510 * 3353 hypothetical protein CAETHG_2170 CUU_c00520 * 3354 hypothetical protein CAETHG_2171 CLJU_cOO53O * 3355 Uncharacterized conserved protein CAETHG_2172 CLJU_c00540 * 3356 hypothetical protein CAETHG_2737 CUU_cO641O * 3357 hypothetical protein CAETHG_2805 CUU_c07130 * 3358 hypothetical protein CAETHG_2842 CUU_c07490 * 3359 hypothetical protein CAETHG_2858 CUU_c07650 * 3360 FliT protein CAETHG_3054 CUU_c09590 * 3361 Group 1 glycosyltransferases CAETHG_3068 CUU_c09750 * 3362 hypothetical protein CAETHG_3081 CLJU_cO99OO * 3363 hypothetical protein CAETHG_3084 CLJU_cO993O * 3364 carbamoylphosphate synthase, large subunit CAETHG_3089 CUU_c09980 * 3365 carbamoylphosphate synthase, large subunit CAETHG_3090 CUU_c09990 * 3366 hypothetical protein CAETHG_3175 CUU_cl0860 *

- 101 044153

3367 Protein of unknown function (DUF2975) CAETHG_3486 CUU_cl4050 * 3368 Enzyme YgiQ of the superfamily of proteins containing the SAM radical, family UPF0313 CAETHG_3488 CUU_cl4070 * 3369 Subfamily B protein of proteins containing an ATP-binding cassette CAETHG_3489 CUU_cl4080 * 3370 heat shock protein domain-containing protein DnaJ CAETHG_3554 CUU_cl4470 * 3371 HIRAN domain containing protein CAETHG_3555 CLJU_cl4480 * 3372 Acetylesterase/lipase CAETHG_3596 CUU_cl4900 * 3373 hypothetical protein CAETHG_3616 CUU_cl5140 * 3374 protein of unknown function (DUF4179) CAETHG_3714 CUU_cl6200 * 3375 hypothetical protein CAETHG_3725 CUU_cl6310 * 3376 hypothetical protein CAETHG_3727 CUU_cl6330 * 3377 hypothetical protein CAETHG_3831 CUU_cl7190 * 3378 protein of unknown function (DUF4386) CAETHG_3875 CUU_cl7670 * 3379 Protein A of glucose-inhibited fission CAETHG_3964 CUU_cl8570 * 3380 hypothetical protein CAETHG_4030 CUU_cl8960 * 3381 ABC transporter CAETHG_4034 CUU_cl9000 * 3382 Transposase and its inactivated derivatives CAETHG_4054 CUU_cl9190 * 3383 * CUU_c27970 * 3384 * CUU_c27920 * 3385 * CUU_c27910 * 3386 * CUU_c27880 * 3387 * CUU_c27760 * 3388 * CUU_c27750 * 3389 * CUU_c27600 * 3390 * CUU_c27590 * 3391 * CUU_cl6900 * 3392 * CUU_c27370 * 3393 * CUU_c27400 * 3394 * CUU_c27420 * 3395 * CUU_c27430 * 3396 * CUU_c27460 * 3397 * CUU_c27470 * 3398 * CUU_c27500 * 3399 * CUU_c27540 * 3400 * CUU_cl8820 * 3401 * CUU_cl8810 * 3402 * CLJU_cl8800, CUU_cl8780 * 3403 * CUU_cl8790 * 3404 * CUU_cl8770 * 3405 * CUU_cl8710 * 3406 * CUU_c30980 * 3407 * CUU_c37150 * 3408 * CUU_c28930 * 3409 * CUU_c29510 * 3410 * CUU_cl5790 * 3411 * CUU_cl5950 *

- 102 044153

3412 * CUU_c31700 * 3413 * CUU_c31690 * 3414 * CUU_c31680 * 3415 * CUU_c31670 * 3416 * CUU_c31660 * 3417 * CUU_c31650 * 3418 * CUU_c31360 * 3419 * CLJU_c30940 * 3420 * CLJU_c36400 * 3421 * CUU_c31730 * 3422 * CUU_c31760 * 3423 * CUU_c31780 * 3424 * CUU_cl4410 * 3425 * CUU_cl4620 * 3426 * CUU_cl5560 * 3427 * CUU_c05760 * 3428 * CLJU_cl0050 * 3429 * CUU_c28140 * 3430 * CUU_c27980 * 3431 * CUU_c42660 * 3432 * CLJU_c23010 * 3433 * CUU_c31370 * 3434 * CUU_c31320 * 3435 * CUU_c31300 * 3436 * CUU_c31290 * 3437 * CUU_c31280 * 3438 * CUU_c31270 * 3439 * CUU_c31260 * 3440 * CUU_c31250 * 3441 * CUU_c31240 * 3442 * CLJU_c31230 * 3443 * CUU_c31210 * 3444 * CLJU_c31200 * 3445 * CUU_c31190 * 3446 * CUU_c31180 * 3447 * CUU_c31170 * 3448 * CUU_c31160 * 3449 * CUU_c31130 * 3450 * CUU_c31120 * 3451 * CUU_c31110 * 3452 * CLJU_c31090 * 3453 * CUU_c38410 * 3454 * CUU_c08360 * 3455 * CUU_c03680 CLRAG_17070 3456 * CLJU_c09700 CLRAG_13470 3457 * CUU_cl6600 CLRAG_33500 3458 * CUU_cl6640 CLRAG_33530 3459 * CUU_cl6650 CLRAG_33540

- 103 044153

3460 * CUU_cl6660 CLRAG_33560 3461 * CUU_cl6680 CLRAG_33580 3462 * CUU_cl6690 CLRAG_33590 3463 * CUU_cl6700 CLRAG_33600 3464 * CUU_cl8720 CLRAG_16640 3465 * CUU_c22370 CLRAG_32010 3466 * CUU_c22380 CLRAG_32020 3467 * CUU_c22400, CUU_c22430 CLRAG_32040 3468 * CUU_c22410, CUU_c22440 CLRAG_32050 3469 * CUU_c22460 CLRAG_32070 3470 * CUU_c22470 CLRAG_32080 3471 * CUU_c22550 CLRAG_32110 3472 * CUU_c22700 CLRAG_02150 3473 * CUU_c29580 CLRAG_35570 3474 * CUU_c31450 CLRAG_16350 3475 * CUU_c31570 CLRAG_16390 3476 * CUU_c32430 CLRAG_03340 3477 * CUU_c32490 CLRAG_03370 3478 * CUU_c32680 CLRAG_29350 3479 * CUU_c32690 CLRAG_15640 3480 * CUU_c32700 CLRAG_15630 3481 * CUU_c32710 CLRAG_15620 3482 * CUU_c32720 CLRAG_15610 3483 * CUU_c37770 CLRAG_37190 3484 * CUU_c37900 CLRAG_37290 3485 * CUU_c37950 CLRAG_37340 3486 * CUU_c37960 CLRAG_37350 3487 protein containing a domain with a 4Fe4S dicluster CAETHG_2998 CUU_c09040 * 3488 lstB-like ATP-binding protein CAETHG_3079 CUU_cO988O * 3489 * CUU_c27650 * 3490 * CUU_c27380, CUU_c30970 * 3491 Multimeric flavodoxin WrbA CAETHG_1029 CUU_c30220 * 3492 * CUU_c26180 CLRAG_04260 3493 peptide deformylase CAETHG_3721 CUU_cl6270 * 3494 * CUU_c03640 * 3495 * CUU_c31220 * 3496 Site-specific recombinase XerD CAETHG_3070 CUU_c09770 * 3497 Homeodomain type phBC6A51 CAETHG_2149 CUU_c00320 * 3498 Phage TP901 family phage roulette protein, core region CAETHG_2158 CUU_c00400 * 3499 * CUU_c36480 * 3500 * CUU_c31330 * 3501 * CUU_c31310 * 3502 * CUU_c31070 * 3503 * CUU_cl6810 CLRAG_33720 3504 * CUU_c38600 *

- 104 044153

3505 * CUU_cl4340 * 3506 exo-poly-alpha-galacturonosidase CAETHG_0930 CLJU_c29360 * 3507 hypothetical protein CAETHG_1050 CLJU_c30450 * 3508 * CUU_c38080 CLRAG_37450 3509 maltose-O-acetyltransferase CAETHG_0520 CUU_c24570 * 3510 putative acetyltransferase CAETHG_1163 CLJU_c32330 * 3511 * CUU_c27630 * 3512 * CLJU_c37730 CLRAG_37150 3513 * CUU_c37740 CLRAG_37160 3514 * CUU_c32660 CLRAG_29360 3515 * CUU_c27610 * 3516 * CUU_c27950 * 3517 * CUU_c31080 * 3518 * CUU_c30310 * 3519 transporter family protein 2- hydroxycarboxylates CAETHG_0599 CUU_c25300 * 3520 MFS-CP family transporter, cyanate transporter CAETHG_3728 CUU_cl6340 * 3521 RraA family protein CAETHG_1374 CUU_c34770 * 3522 * CUU_c37720 CLRAG_37140 3523 * CUU_c37750 CLRAG_37170 3524 * CUU_cl2090 * 3525 * CUU_cl2040 * 3526 * CUU_cl2080 * 3527 * CUU_cl2070 * 3528 * CUU_cl2060 * 3529 * CUU_cl2050 * 3530 putative transcriptional regulator CAETHG_2140 CLJU_cOO23O * 3531 * CUU_cl6610 CLRAG_33510 3532 * CUU_c32480 CLRAG_03360 3533 * CUU_c32510 CLRAG_03390 3534 Fur family transcriptional regulator, ferric iron uptake regulator CAETHG_3722 CUU_cl6280 * 3535 * CUU_c37710 CLRAG_37130 3536 N-terminal helical region of flagellin CAETHG_3092 CUU_cl0010 * 3537 flagellin CAETHG_3065 CUU_c09710 * 3538 flagellin CAETHG_3055 CUU_c09600 * 3539 * CUU_c37820 CLRAG_37240 3540 Protein 26 general stress CAETHG_1154 CUU_c32260 * 3541 * CUU_cl5570 * 3542 Glycosyltransferase involved in cell wall bisynthesis CAETHG_2599 CUU_c05220 * 3543 Group 1 glycosyltransferases CAETHG_2602 CUU_c05230 * 3544 hypothetical protein CAETHG_2604 CUU_c05250 * 3545 GT2 family glycosyltransferase CAETHG_4032 CUU_cl8980 * 3546 * CUU_cl4310 * 3547 * CUU_c27410 * 3548 Phage integrase family protein CAETHG_3072 CLJU_cO979O * 3549 * CUU_c38030 CLRAG_37400

- 105 044153

3550 * CUU_c38040 CLRAG_37410 3551 * CUU_c37220 * 3552 DNA-binding transcriptional regulator of the LysR family CAETHG_0635 CUU_c25660 * 3553 DNA-binding transcriptional regulator of the LysR family CAETHG_1372 CUU_c34750 * 3554 * CUU_c37910 CLRAG_37300 3555 DNA-binding transcriptional regulator of the MarR family CAETHG_3724 CUU_cl6300 * 3556 GHKL domain-containing protein CAETHG_3730 CUU_cl6360 * 3557 hypothetical protein CAETHG_1007 CLJU_c30090 * 3558 Helix-loop-helix domain CAETHG_2014 CUU_c41850 * 3559 * CUU_c38710 * 3560 * CUU_c28070 * 3561 * CUU_c37860 CLRAG_37250 3562 * CLJU_c38000, CUU_c38020 CLRAG_37370 3563 * CUU_cl6030 * 3564 Na+/H+ antiporter NhaC CAETHG_1537 CLJU_c36290 * 3565 methyl acceptor chemotaxis protein CAETHG_3723 CUU_cl6290 * 3566 * CUU_c28030 * 3567 * CUU_cl5520 CLRAG_32600 3568 Protein containing a methyltransferase domain CAETHG_1164 CUU_c32340 * 3569 * CUU_c22690 CLRAG_02160 3570 * CUU_c28120 CLRAG_09080 3571 * CUU_c38100 CLRAG_37470 3572 * CUU_c38090 CLRAG_37460 3573 * CUU_c27930 * 3574 Nucleoside diphosphate sugar epimerase CAETHG_0073 CUU_cl9930 * 3575 NADPH-dependent glutamate synthase, beta chain CAETHG_1033 CUU_c30260 * 3576 * CUU_c38670 * 3577 * CUU_c22630 CLRAG_02220 3578 * CUU_c22640 CLRAG_02210 3579 * CUU_c22670 CLRAG_02180 3580 * CUU_c22650 CLRAG_02200 3581 * CUU_c22660 CLRAG_02190 3582 * CUU_c27860 * 3583 * CUU_c37160 * 3584 * CLJU_c37870, CUU_c37890 CLRAG_37260 3585 Transcription regulator, contains the HTH domain of the XRE family CAETHG_2139 CLJU_cOO22O * 3586 * CUU_c31380 * 3587 phage-like integrase CAETHG_3071 CUU_c09780 * 3588 Phage integrase family protein CAETHG_3073 CUU_c09800 * 3589 Phage integrase, N-terminal SAM-like domain CAETHG_3074 CUU_c09810 * 3590 * CUU_c32470 CLRAG_03350 3591 Phage integrase family protein CAETHG_0071 CUU_cl9910 * 3592 * CUU_c03690 CLRAG_17060

- 106 044153

3593 phage terminase, small subunit CAETHG_2152 CLJU_cOO35O * 3594 hypothetical protein CAETHG_1031 CUU_c30240 * 3595 undecaprenide diphosphatase CAETHG_3807 CUU_cl6970 * 3596 D-3-phosphoglycerate dehydrogenase CAETHG_1373 CUU_c34760 * 3597 * CUU_c32650 CLRAG_29370 3598 * CUU_c27940 * 3599 * CUU_c27960 * 3600 DNA-binding transcriptional regulator of the MerR family CAETHG_0072 CUU_cl9920 * 3601 * CUU_c27580 * 3602 * CUU_c27510 * 3603 Protein containing a PAS domain with an S box CAETHG_0094, CAETHG_0472 CLJU_c24140, CLJU_c24060, CLJU_c20130 * 3604 * CUU_c21760 * 3605 KS spore germination protein CAETHG_1735 CUU_c38870 * 3606 CA spore germination protein CAETHG_1733 CUU_c38850 * 3607 Spore germination protein CAETHG_1734 CUU_c38860 * 3608 * CUU_c38390 * 3609 * CLJU_c22420, CUU_c22450 CLRAG_32060 3610 DNA-binding transcriptional regulator of the MarR family CAETHG_0719 CUU_c26380 * 3611 Protein containing a PAS domain with an S box CAETHG_1884 CLJU_c40410 * 3612 DNA-binding transcriptional regulator of the MarR family CAETHG_3726 CUU_cl6320 * 3613 * CUU_c27390 * 3614 * CUU_cl5550 * 3615 * CLJU_cO7O9O, CUU_c22680 CLRAG_02170 3616 Sugar phosphate permease CAETHG_1375 CUU_c34780 * 3617 * CUU_c37430 * 3618 * CUU_c37420 * 3619 DDE transposase domain-containing protein CAETHG_0888 CUU_c28920 * 3620 Transposase CAETHG_3075 CUU_c09820 * 3621 hypothetical protein CAETHG_3078 CUU_c09860 * 3622 * CUU_c38690 * 3623 * CUU_cl4350 * 3624 * CUU_c29570 CLRAG_35560 3625 RNA polymerase sigma factor 70 ECF subfamilies CAETHG_3713 CUU_cl6190 * 3626 * CUU_c27730 * 3627 * CUU_cl4370 * 3628 * CLJU_c27800, CUU_c27320 * 3629 * CLJU_c27810, CUU_c27330 * 3630 threonine synthase 4.2.3.1, 4.2.99.2 CAETHG_1882 CLJU_c40360 * 3631 Glycosyltransferase involved in cell wall bisynthesis CAETHG_3067 CUU_c09740 * 3632 transcriptional regulator of transport of aroF, aroG, tyrA and aromatic amino acids CAETHG_1538 CUU_c36300 * 3633 * CLJU_c28060, *

- 107 044153

CUU_c28040 3634 DNA-binding transcriptional regulator of the GntR family CAETHG_1056 CUU_c30510 * 3635 HxIR family transcriptional regulator CAETHG_1153 CUU_c32250 * 3636 DNA-binding transcriptional regulator of the MarR family CAETHG_3719 CUU_cl6250 * 3637 * CUU_c27850 * 3638 * CUU_c38610 * 3639 * CUU_cl4330 * 3640 * CUU_c26190 CLRAG_04270 3641 * CUU_cl2020 * 3642 NhaC family transporter CAETHG_1881 CLJU_c40350 * 3643 Carrier of di- and tricarboxylates CAETHG_0600 CUU_c25310 * 3644 two-component transcription regulator of the LytTR family CAETHG_1006 CUU_c30080 * 3645 two-component transcription regulator of the LytTR family CAETHG_3731 CUU_cl6370 * 3646 uroporphyrinogen decarboxylase CAETHG_1037 CUU_c30300 * 3647 hypothetical protein CAETHG_0137 * * 3648 hypothetical protein CAETHG_0195 * * 3649 hypothetical protein CAETHG_0270 * * 3650 ABC transporter, ATP-binding protein CAETHG_0294 * * 3651 hypothetical protein CAETHG_0453 * * 3652 elongation factor protein containing a tetracycline resistance domain 6.3.5.5 CAETHG_0514 * * 3653 hypothetical protein 2.7.7.22 CAETHG_0516 * * 3654 hypothetical protein CAETHG_0524 * * 3655 hypothetical protein CAETHG_0528 * * 3656 hypothetical protein CAETHG_0549 * * 3657 Amidase related to nicotinamidase 3.3.2.1 CAETHG_0695 * * 3658 hypothetical protein CAETHG_0701 * * 3659 hypothetical protein CAETHG_0763 * * 3660 hypothetical protein CAETHG_0793 * * 3661 InsO transposase and its inactivated derivatives CAETHG_0814, CAETHG_2268, CAETHG_1100 * * 3662 transposase CAETHG_0815, CAETHG_2269, CAETHG_1101 * * 3663 Na+:H+ antiporter of the NhaA family CAETHG_0953 * CLRAG_21450 3664 HxIR family transcription regulator CAETHG_0960 * * 3665 hypothetical protein 1.3.99.1 CAETHG_1022 * CLRAG_15760 3666 CRISPR-associated protein Cas2 CAETHG_1394 * * 3667 CRISP-associated protein Casl CAETHG_1395 * * 3668 CRISPR-associated exonuclease Cas4 CAETHG_1396 * * 3669 hypothetical protein CAETHG_1434 * * 3670 carbon monoxide dehydrogenase, catalytic subunit CAETHG_1620 * * 3671 hypothetical protein CAETHG_1636 * * 3672 ATP-dependent DNA helicase RecG CAETHG_1648 * CLRAG_29890 3673 PilZ domain-containing protein CAETHG_1696 * CLRAG_20850 3674 hypothetical protein CAETHG_2261 * *

- 108 044153

3675 Protein containing a PAS domain with an S box CAETHG_2512 * CLRAG_37760 3676 2,3-dimethylmalate lyase CAETHG_2513 * CLRAG_37770 3677 Sugar phosphate permease CAETHG_2514 * CLRAG_37780 3678 YgiT-type zinc finger domain-containing protein CAETHG_2556 * * 3679 RayT transposase, which mobilizes the REP element CAETHG_2561 * CLRAG_38230 3680 hypothetical protein CAETHG_2562 * * 3681 WxcM-like protein, C-terminal domain CAETHG_2608 * * 3682 dTDP-4-amino-4,6- dideoxygalactose transaminase CAETHG_2609 * * 3683 mannose-1-phosphate guanylyltransferase / Mannose-6-phosphate isomerase CAETHG_2636 * CLRAG_38780 3684 PilA type IV pili assembly protein CAETHG_2644 * CLRAG_06750 3685 type II secretion system protein E (GspE) CAETHG_2645 * CLRAG_06760 3686 Pile type IV pili assembly protein CAETHG_2646 * CLRAG_06770 3687 PilΜ type IV pili assembly protein CAETHG_2647 * CLRAG_06780 3688 PilO type IV pili assembly protein CAETHG_2649 * CLRAG_06790 3689 protein containing a prepilin-type N-terminal hydrolysis/methylation domain CAETHG_2650 * CLRAG_06800 3690 hypothetical protein CAETHG_2651 * CLRAG_06810 3691 protein containing a prepilin-type N-terminal hydrolysis/methylation domain CAETHG_2652 * CLRAG_06820 3692 N-terminal PilX domain CAETHG_2653 * CLRAG_06830 3693 putative esterase CAETHG_2672 * * 3694 Purpuric acid phosphatase, N-terminal domain CAETHG_2695 * * 3695 methyl acceptor sensor chemotaxis transducer CAETHG_2856 * * 3696 hypothetical protein CAETHG_2944 * * 3697 hypothetical protein CAETHG_3435 * * 3698 ATP-dependent helicase IRC3 CAETHG_3519 * CLRAG_09710 3699 hypothetical protein CAETHG_3521 * CLRAG_09730 3700 hypothetical protein CAETHG_3522 * CLRAG_09740 3701 AAA domain-containing protein (dynein-related protein subfamily) CAETHG_3525 * * 3702 hypothetical protein CAETHG_3526 * * 3703 hypothetical protein CAETHG_3538 * CLRAG_20350 3704 DNA repair exonuclease SbcCD, nuclease subunit CAETHG_3542 * CLRAG_09860 3705 Uncharacterized YhaN protein CAETHG_3543 * CLRAG_09870 3706 Protein of the PD-(D/E)XK nuclease superfamily CAETHG_3544 * CLRAG_09670 3707 hypothetical protein CAETHG_3546 * CLRAG_09690 3708 ATP-dependent helicase IRC3 CAETHG_3547 * * 3709 hypothetical protein CAETHG_3549 * * 3710 hypothetical protein CAETHG_3598 * * 3711 DNA-binding transcriptional regulator of the MarR family CAETHG_3658 * CLRAG_32640 3712 Protein containing a methyltransferase domain CAETHG_3659 * CLRAG_32650 3713 phosphinotricin acetyltransferase CAETHG_3660 * CLRAG_32660 3714 probable redox protein of the C_GCAxxG_C_C family CAETHG_3661 * CLRAG_32670 3715 DGC domain-containing protein CAETHG_3668 * CLRAG_32750

- 109 044153

3716 DGC domain-containing protein CAETHG_3669 * CLRAG_32760 3717 Glycine cleavage system H protein CAETHG_3670 * CLRAG_32770 3718 NAD-dependent Dihydropyrimidine dehydrogenase, PgeA subunit CAETHG_3671 * CLRAG_32780 3719 hypothetical protein CAETHG_3672 * CLRAG_32790 3720 hypothetical protein CAETHG_3673 * CLRAG_32810 3721 zinc-dependent peptidase CAETHG_3676 * CLRAG_32840 3722 DNA-binding transcriptional regulator containing the XRE family HTH domain CAETHG_3752 * * 3723 hypothetical protein CAETHG_3753 * CLRAG_33400 3724 hypothetical protein CAETHG_3754 * CLRAG_33410 3725 DNA segregation ATPase FtsK/SpollE, S-DNA-T family CAETHG_3755 * CLRAG_33420 3726 restriction protein CAETHG_3757 * CLRAG_33440 3727 DNA helicase-2 / ATP-dependent DNA helicase PcgA CAETHG_3803 * CLRAG_33820 3728 hypothetical protein CAETHG_3810 * * 3729 arsenic pump membrane protein CAETHG_3985 * CLRAG_16620 3730 protein of unknown function (DUF3794) CAETHG_3987 * CLRAG_16610 3731 hypothetical protein CAETHG_3988 * CLRAG_16600 3732 hypothetical protein CAETHG_3989, CAETHG_3990 * CLRAG_16590 3733 hypothetical protein CAETHG_3991 * CLRAG_16570 3734 SpoOE-like regulatory protein sporulation CAETHG_3995 * CLRAG_16530 3735 Cupin domain-containing protein 5.3.1.8 CAETHG_3997 * CLRAG_16510 3736 autoinducer kinase 2 (AI-2) CAETHG_3998 * CLRAG_16500 3737 DNA-binding transcriptional regulator LsrR of the DeoR family CAETHG_3999 * CLRAG_16490 3738 transport system AI-2, ATP-binding protein CAETHG_4000 * CLRAG_16480 3739 transport system AI-2, permease protein CAETHG_4001 * CLRAG_16470 3740 transport system AI-2, permease protein CAETHG_4002 * CLRAG_16460 3741 transport system AI-2, substrate-binding protein CAETHG_4003 * CLRAG_16450 3742 putative aldolase autoinducer-2 (AI2) CAETHG_4004 * CLRAG_16440 3743 hypothetical protein CAETHG_4005 * CLRAG_16430 3744 GT2 family glycosyltransferase CAETHG_4007, CAETHG_4012 * CLRAG_16410 3745 Peptidoglya n/xyl n/chitinde cetylase of the PgdA/CDAl family CAETHG_4008 * CLRAG_40260 3746 UDP-glucose-6-dehydrogenase 1.1.1.22 CAETHG_4009 * CLRAG_40250 3747 Glycosyltransferase-like protein families 2 CAETHG_4010 * CLRAG_40230 3748 Family 2 glycosyltransferase CAETHG_4011, CAETHG_4013, CAETHG_4014 * CLRAG_40210 3749 Spore maturation protein CgeB CAETHG_4015 * CLRAG_40170 3750 hypothetical protein CAETHG_4016 * CLRAG_40160 3751 hypothetical protein CAETHG_4021 * CLRAG_40100 3752 hypothetical protein CAETHG_4022 * CLRAG_40090 3753 * * CLRAG_38840 3754 * * CLRAG_39170

- 110 044153

3755 * * CLRAG_39160 3756 * * CLRAG_39140 3757 * * CLRAG_39110 3758 * * CLRAG_39100 3759 * * CLRAG_29850 3760 * * CLRAG_33000 3761 * * CLRAG_33280 3762 * * CLRAG_33290 3763 * * CLRAG_40220 3764 * * CLRAG_17980 3765 * * CLRAG_03540 3766 * * CLRAG_06340 3767 * * CLRAG_06490 3768 * * CLRAG_09680 3769 * * CLRAG_32280 3770 * * CLRAG_32270 3771 * * CLRAG_32400 3772 * * CLRAG_32390 3773 * * CLRAG_32380 3774 * * CLRAG_32370 3775 * * CLRAG_24810 3776 * * CLRAG_30620 3777 * * CLRAG_30760 3778 * * CLRAG_32420 3779 * * CLRAG_01000 3780 * * CLRAG_00960 3781 * * CLRAG_02850 3782 * * CLRAG_02860 3783 * * CLRAG_02870 3784 * * CLRAG_02880 3785 * * CLRAG_02900 3786 * * CLRAG_02910 3787 * * CLRAG_02920 3788 * * CLRAG_02950 3789 * * CLRAG_02960 3790 * * CLRAG_02970 3791 * * CLRAG_02980 3792 * * CLRAG_02990 3793 * * CLRAG_03000 3794 * * CLRAG_03010 3795 * * CLRAG_03310 3796 * * CLRAG_03330 3797 * * CLRAG_15190 3798 * * CLRAG_15180 3799 * * CLRAG_09910 3800 * * CLRAG_32560 3801 * * CLRAG_30530 3802 * * CLRAG_32700

- 111 044153

3803 * * CLRAG_14810 3804 * * CLRAG_25230 3805 * * CLRAG_25290 3806 * * CLRAG_20440 3807 * * CLRAG_37570 3808 * * CLRAG_26360 3809 * * CLRAG_37610 3810 * * CLRAG_36020 3811 * * CLRAG_36040 3812 * * CLRAG_36050 3813 * * CLRAG_36060 3814 * * CLRAG_09130 3815 * * CLRAG_05640 3816 * * CLRAG_16370 3817 * * CLRAG_23850 3818 * * CLRAG_13360 3819 * * CLRAG_13380 3820 * CUU_c01630, CUU_c38500, CUU_c37040, CUU_c31010, CUU_cl7540 * 3821 * CUU_cl4540 * 3822 * CUU_cl5870 * 3823 * CUU_c03760 * 3824 * CUU_c37840 * 3825 * CLJU_c00490 * 3826 * CUU_c01550 * 3827 * CUU_c01590 * 3828 * CLJU_c02010 * 3829 * CUU_c02510 * 3830 * CUU_c03280 * 3831 * CUU_c03290 * 3832 * CUU_c03300 * 3833 * CUU_c03340 * 3834 * CUU_c03350 * 3835 * CUU_c03360 * 3836 * CUU_c03410 * 3837 * CUU_c03450 * 3838 * CUU_c03460 * 3839 * CUU_c03490 * 3840 * CUU_c03500 * 3841 * CUU_c03510 * 3842 * CUU_c03570 * 3843 * CUU_c03580 * 3844 * CUU_c03590 * 3845 * CUU_c03600 * 3846 * CUU_c03630 * 3847 * CUU_c03700 *

- 112 044153

3848 * CLJU_c03730 * 3849 * CUU_c03750 * 3850 * CUU_c03790 * 3851 * CUU_c03800 * 3852 * CLJU_c04140 * 3853 * CUU_c04260 * 3854 * CUU_c04540 * 3855 * CUU_c04850 * 3856 * CUU_c05260 * 3857 * CUU_c05360 * 3858 * CUU_c05370 * 3859 * CUU_c05590 * 3860 * CUU_c05810 * 3861 * CUU_c06880 * 3862 * CUU_c07740 * 3863 * CUU_c08420 * 3864 * CUU_c08940 * 3865 * CUU_c09720 * 3866 * CUU_c09850 * 3867 * CUU_cl0030 * 3868 * CUU_cl0790 * 3869 * CUU_cl0810 * 3870 * CUU_cl0890 * 3871 * CUU_cl2030 * 3872 * CUU_cl2660 * 3873 * CUU_cl2760 * 3874 * CUU_cl3500 * 3875 * CUU_cl3510 * 3876 * CUU_cl3590 * 3877 * CLJU_cl4040 * 3878 * CUU_cl4440 * 3879 * CUU_cl4490 * 3880 * CUU_cl4500 * 3881 * CUU_cl4510 * 3882 * CUU_cl4520 * 3883 * CUU_cl4530 * 3884 * CUU_cl4550 * 3885 * CUU_cl4560 * 3886 * CUU_cl4570 * 3887 * CUU_cl4580 * 3888 * CUU_cl4590 * 3889 * CUU_cl4600 * 3890 * CUU_cl4610 * 3891 * CUU_cl4690 * 3892 * CUU_cl4760 * 3893 * CUU_cl4830 * 3894 * CUU_cl5030 * 3895 * CUU_cl5040 *

- 113 044153

3896 * CUU_cl5390 * 3897 * CUU_cl5850 * 3898 * CUU_cl5880 * 3899 * CUU_cl5890 * 3900 * CUU_cl5900 * 3901 * CUU_cl5970 * 3902 * CUU_cl5980 * 3903 * CUU_cl6010 * 3904 * CUU_cl6180 * 3905 * CUU_cl6560 * 3906 * CUU_cl6570 * 3907 * CUU_cl6620 * 3908 * CUU_cl6630 * 3909 * CUU_cl6670 * 3910 * CUU_cl6710 * 3911 * CUU_cl6730 * 3912 * CUU_cl6740 * 3913 * CUU_cl6750 * 3914 * CUU_cl6760 * 3915 * CUU_cl6780 * 3916 * CUU_cl6790 * 3917 * CUU_cl6800 * 3918 * CUU_cl6820 * 3919 * CUU_cl6850 * 3920 * CUU_cl6860 * 3921 * CUU_cl6870 * 3922 * CUU_cl6880 * 3923 * CUU_cl6890 * 3924 * CUU_cl6910 * 3925 * CUU_cl6920 * 3926 * CUU_cl8170 * 3927 * CUU_cl8840 * 3928 * CUU_c22480 * 3929 * CUU_c22490 * 3930 * CUU_c23350 * 3931 * CUU_c24820 * 3932 * CUU_c27010 * 3933 * CUU_c27870 * 3934 * CUU_c28150 * 3935 * CLJU_c30070 * 3936 * CUU_c30180 * 3937 * CLJU_c30190 * 3938 * CUU_c30380 * 3939 * CUU_c30570 * 3940 * CUU_c30580 * 3941 * CUU_c30830 * 3942 * CUU_c30840 * 3943 * CLJU_c30910 *

- 114 044153

3944 * CUU_c31060 * 3945 * CUU_c31100 * 3946 * CUU_c31140 * 3947 * CUU_c31150 * 3948 * CUU_c31350 * 3949 * CUU_c31410 * 3950 * CUU_c31420 * 3951 * CUU_c31430 * 3952 * CUU_c31440 * 3953 * CUU_c31470 * 3954 * CUU_c31500 * 3955 * CUU_c31520 * 3956 * CUU_c31530 * 3957 * CUU_c31560 * 3958 * CUU_c31580 * 3959 * CUU_c31770 * 3960 * CLJU_c32440 * 3961 * CUU_c32450 * 3962 * CUU_c32460 * 3963 * CUU_c32590 * 3964 * CUU_c32600 * 3965 * CUU_c32610 * 3966 * CUU_c32620 * 3967 * CUU_c32670 * 3968 * CUU_c33460 * 3969 * CUU_c35370 * 3970 * CUU_c35820 * 3971 * CUU_c35990 * 3972 * CUU_c36270 * 3973 * CUU_c36280 * 3974 * CUU_c36380 * 3975 * CUU_c36390 * 3976 * CUU_c36420 * 3977 * CUU_c36430 * 3978 * CUU_c36490 * 3979 * CUU_c36540 * 3980 * CUU_c36580 * 3981 * CUU_c36590 * 3982 * CUU_c36600 * 3983 * CUU_c36610 * 3984 * CUU_c36630 * 3985 * CUU_c36640 * 3986 * CUU_c37980 * 3987 * CUU_c37990 * 3988 * CUU_c38570 * 3989 * CUU_c38730 * 3990 * CUU_c38750 * 3991 * CUU_c38760 *

- 115 044153

3992 * CUU_c39050 * 3993 * CUU_c40150 * 3994 * CUU_c40170 * 3995 * CUU_c40190 * 3996 * CUU_c40380 * 3997 * CLJU_c40400 * 3998 * CUU_c42670 * 3999 * CUU_cl4630 * 4000 * CUU_c30860 * 4001 * CUU_c05280 * 4002 * CUU_c05240 * 4003 * CUU_cl6840 * 4004 * CUU_c03390, CUU_c36550 * 4005 * CUU_c03550 * 4006 * CLJU_c03530 * 4007 * CUU_c03370 * 4008 * CUU_c03380, CUU_c36560 * 4009 * CUU_c03420 * 4010 * CUU_c03430, CUU_c36520 * 4011 * CUU_c03560 * 4012 * CUU_c03650 * 4013 * CUU_c03660 * 4014 * CUU_c03670 * 4015 * CUU_cl6720 * 4016 * CUU_cl6770 * 4017 * CUU_c31460 * 4018 * CUU_c31480 * 4019 * CUU_c31590 * 4020 * CUU_c31630 * 4021 * CUU_c31640 * 4022 * CUU_c36530 * 4023 * CUU_c36570 * 4024 * CUU_c27680 * 4025 * CUU_c22500 * 4026 * CUU_c27660 * 4027 * CUU_c28970 * 4028 * CUU_c28980 * 4029 * CUU_c28990 * 4030 * CUU_c01650, CUU_c38520, CUU_c37060, CUU_c31030, CUU_cl7520 * 4031 * CUU_c30170 * 4032 * CUU_cl6830 * 4033 * CUU_cl4770 * 4034 * CUU_c36450 *

- 116 044153

4035 * CUU_c37830 * 4036 * CUU_cl8950 * 4037 * CLJU_c30990 * 4038 * CUU_c36410 * 4039 * CUU_c31510 * 4040 * CUU_c30850 * 4041 * CUU_c37850 * 4042 * CUU_c05270 * 4043 * CUU_c05290 * 4044 * CLJU_c05300 * 4045 * CUU_c09730 * 4046 * CUU_c36460 * 4047 * CUU_c32630 * 4048 * CUU_cl4020 * 4049 * CUU_cl4030 * 4050 * CUU_c25560, CUU_c28490, CUU_c27520 * 4051 * CUU_c38740 * 4052 * CUU_c27670 * 4053 * CUU_c28020 * 4054 * CUU_c03480 * 4055 * CUU_c22530 * 4056 * CUU_c27550 * 4057 * CUU_cl5830 * 4058 * CUU_c03780 * 4059 * CUU_cl5860 * 4060 * CUU_c03610 * 4061 * CUU_c36680 * 4062 * CUU_c03540 * 4063 * CUU_c36650 * 4064 * CUU_c03740 * 4065 * CUU_c03440, CUU_c36500 * 4066 * CUU_c31610 * 4067 * CUU_c03520 * 4068 * CUU_c31400 * 4069 * CUU_c31390 * 4070 * CUU_c31620 * 4071 * CUU_c03470 * 4072 * CUU_c03620 * 4073 * CUU_c03720 * 4074 * CUU_c31490 * 4075 * CUU_c36440 * 4076 * CUU_cl6580 * 4077 * CUU_c30870 * 4078 * CLJU_c03400 * 4079 * CLJU_c03770 * 4080 * CUU_c36620 *

- 117 044153

4081 * CLJU_c01620, CLJU_c38490, CLJU_c37030, CUU_c31000, CUU_cl7550 * 4082 * CUU_c39040 * 4083 * CUU_c22390 * 4084 * CUU_c31550 * 4085 * CUU_c31710 * 4086 * CUU_c31720 * 4087 * CUU_c36660 * 4088 * CUU_c36670 * 4089 * CUU_cO987O * 4090 * CUU_c37080 * 4091 * CLJU_c01640, CLJU_c38510, CLJU_c37050, CLJU_c31020, CUU_cl7530 * 4092 * CUU_c03310 * 4093 * CUU_c28530 * 4094 * CLJU_c39030 * 4095 * CLJU_c39060, CUU_c39070 * 4096 * CUU_c01660, CLJU_c38530, CLJU_c37070, CUU_c31040, CUU_cl7510 * 4097 * CUU_c03330 * 4098 * CUU_c03320 * 4099 * CUU_cl5920 * 4100 * CUU_c36510 * 4101 tripeptidaminopeptidase CAETHG_0006 * * 4102 hypothetical protein CAETHG_0053 * * 4103 Response regulator receiver domain-containing protein CAETHG_0055 * * 4104 exonuclease SbcC CAETHG_0114 * * 4105 methyl acceptor chemotaxis protein CAETHG_0120 * * 4106 hypothetical protein CAETHG_0152 * * 4107 Protein containing a domain that binds the 2Fe25-iron-sulfur cluster CAETHG_0157 * * 4108 Tetratricopeptide repeat-containing protein CAETHG_0236 * * 4109 Protein family glycerophosphoryl diester phosphodiesterase CAETHG_0268 * * 4110 Leucylaminopeptidase (aminopeptidase T) CAETHG_0279 * * 4111 AgoM protein CAETHG_0280 * * 4112 hypothetical protein CAETHG_0282 * * 4113 Uncharacterized membrane protein of the oligopeptide transporter (OPT) family CAETHG_0283 * * 4114 purine catabolism regulatory protein CAETHG_0284 * * 4115 hypothetical protein CAETHG_0325 * * 4116 hypothetical protein CAETHG_0326 * *

- 118 044153

4117 hypothetical protein CAETHG_0331 * * 4118 hypothetical protein CAETHG_0336 * * 4119 Protein of the AcrB/AcrD/AcrF family CAETHG_0392 * * 4120 hypothetical protein CAETHG_0399 * * 4121 NNP family MFS transporter, nitrate/nitrite transporter CAETHG_0439 * * 4122 hypothetical protein CAETHG_0489 * * 4123 hypothetical protein CAETHG_0494 * * 4124 hypothetical protein CAETHG_0519 * * 4125 hypothetical protein CAETHG_0547 * * 4126 hypothetical protein CAETHG_0548 * * 4127 hypothetical protein CAETHG_0567 * * 4128 ATP-dependent DNA helicase RecQ CAETHG_0595 * * 4129 hypothetical protein CAETHG_0624 * * 4130 hypothetical protein CAETHG_0632 * * 4131 endoglucanase CAETHG_0687 * * 4132 hypothetical protein CAETHG_0688 * * 4133 hypothetical protein CAETHG_0689 * * 4134 Protein containing the N-terminal domain of SNF2 family proteins CAETHG_0690 * * 4135 Protein containing the N-terminal domain of SNF2 family proteins CAETHG_0691 * * 4136 protein containing the SAM radical and an additional 4Pe45-binding domain SPASM CAETHG_0692 * * 4137 hypothetical protein CAETHG_0693 * * 4138 hypothetical protein CAETHG_0694, CAETHG_3528 * * 4139 epoxyqueuosine reductase CAETHG_0713 * * 4140 hypothetical protein CAETHG_0766 * * 4141 hypothetical protein CAETHG_0790 * * 4142 hypothetical protein CAETHG_0798 * * 4143 hypothetical protein CAETHG_0809 * * 4144 Nuclease superfamily protein PD-(D/E)XK CAETHG_0837 * * 4145 autoinducible cyclic lactone peptide CAETHG_0845 * * 4146 hypothetical protein CAETHG_0851 * * 4147 hypothetical protein CAETHG_0877 * * 4148 Uncharacterized membrane protein YcaP family DUF421 CAETHG_0951 * * 4149 hypothetical protein CAETHG_0952 * * 4150 putative transposase CAETHG_0954 * * 4151 esterase CAETHG_0962 * * 4152 GDSL-like protein family lipases/acylhydrolases CAETHG_0963 * * 4153 PhoH-like ATPase CAETHG_0970 * * 4154 GHKL domain-containing protein CAETHG_1008 * * 4155 hypothetical protein CAETHG_1011 * * 4156 hypothetical protein CAETHG_1017 * * 4157 hypothetical protein CAETHG_1018 * * 4158 hypothetical protein CAETHG_1019 * * 4159 hypothetical protein CAETHG_1020 * *

- 119 044153

4160 DNA or RNA helicase superfamily II CAETHG_1021 * * 4161 hypothetical protein CAETHG_1023 * * 4162 methyl acceptor chemotaxis protein CAETHG_1061 * * 4163 Protein of the transglutaminase-like protein family CAETHG_1087 * * 4164 Putative binding protein cell wall CAETHG_1088 * * 4165 hypothetical protein CAETHG_1094 * * 4166 protein of unknown function (DUF4868) CAETHG_1095 * * 4167 hypothetical protein CAETHG_1096 * * 4168 hypothetical protein CAETHG_1099 * * 4169 Predicted secreted protein CAETHG_1102 * * 4170 Protein containing a C-terminal tetratricopeptide repeat Fisl CAETHG_1104 * * 4171 phage-like protein CAETHG_1105 * * 4172 hypothetical protein CAETHG_1106 * * 4173 hypothetical protein CAETHG_1107 * * 4174 hypothetical protein CAETHG_1157 * * 4175 hypothetical protein CAETHG_1158 * * 4176 hypothetical protein CAETHG_1213 * * 4177 hypothetical protein CAETHG_1233 * * 4178 capD, capsule polysaccharide biosynthesis protein CAETHG_1316 * * 4179 tyrosyl-tRNA synthetase CAETHG_1329 * * 4180 hypothetical protein CAETHG_1362 * * 4181 hypothetical protein CAETHG_1378 * * 4182 CRISPR-associated endonuclease/helicase Cas3 CAETHG_1397 * * 4183 CRISPR-associated protein Cas5h CAETHG_1398 * * 4184 CRISPR-associated protein Csh2 CAETHG_1399 * * 4185 CRISPR-associated protein Cshl CAETHG_1400 * * 4186 CRISPR-associated endoribonuclease Cas6 CAETHG_1401 * * 4187 hypothetical protein CAETHG_1402, CAETHG_1403 * * 4188 hypothetical protein CAETHG_1404 * * 4189 hypothetical protein CAETHG_1405 * * 4190 hypothetical protein CAETHG_1406 * * 4191 hypothetical protein CAETHG_1507 * * 4192 uroporphyrinogen-III decarboxylase-like protein CAETHG_1520 * * 4193 Sensor module with four-helical bundle motif for signal transmission CAETHG_1530 * * 4194 iron-dependent hydrogenase CAETHG_1575 * * 4195 NADH quinone oxidoreductase, subunit G CAETHG_1576 * * 4196 NADH quinone oxidoreductase, subunit E CAETHG_1578 * * 4197 hypothetical protein CAETHG_1640 * * 4198 hypothetical protein CAETHG_1642 * * 4199 hypothetical protein CAETHG_1643 * * 4200 hypothetical protein CAETHG_1645 * * 4201 hypothetical protein CAETHG_1646 * * 4202 hypothetical protein CAETHG_1647 * *

- 120 044153

4203 Protein containing a PLD-like domain CAETHG_1649 * * 4204 Adenine-specific DNA methylase, contains a Zn-ribbon domain CAETHG_1650 * * 4205 Protein of unknown function (DUF3780) CAETHG_1651 * * 4206 Protein containing chitobiase betahexosaminidase C-terminal domain CAETHG_1652 * * 4207 conserved hypothetical protein CAETHG_1653 * * 4208 hypothetical protein CAETHG_1659 * * 4209 hypothetical protein CAETHG_1660 * * 4210 hypothetical protein CAETHG_1661 * * 4211 hypothetical protein CAETHG_1662 * * 4212 hypothetical protein CAETHG_1663 * * 4213 hypothetical protein CAETHG_1664 * * 4214 aspartate kinase CAETHG_1689 * * 4215 TetR family transcriptional regulator CAETHG_1705 * * 4216 hypothetical protein CAETHG_1706 * * 4217 luxR family regulatory protein CAETHG_1709 * * 4218 hypothetical protein CAETHG_1710 * * 4219 M28 family peptidase CAETHG_1711 * * 4220 Chloramphenicol O-acetyltransferase type A CAETHG_1717 * * 4221 Helix-loop-helix domain CAETHG_1724 * * 4222 hypothetical protein CAETHG_1752 * * 4223 endonuclease-3 CAETHG_1772 * * 4224 hypothetical protein CAETHG_1803 * * 4225 ABC transport system, putative permease protein CAETHG_1845 * * 4226 hypothetical protein CAETHG_1852 * * 4227 hypothetical protein CAETHG_1853 * * 4228 hypothetical protein CAETHG_1922 * * 4229 hypothetical protein CAETHG_2012 * * 4230 hypothetical protein CAETHG_2030 * * 4231 [acyl rpynn transport protein]-S- malonyltransferase CAETHG_2047 * * 4232 Fis family regulatory protein CAETHG_2077 * * 4233 hypothetical protein CAETHG_2155 * * 4234 hypothetical protein CAETHG_2164 * * 4235 Protein of unknown function (DUF1015) CAETHG_2212 * * 4236 hypothetical protein CAETHG_2225, CAETHG_2727 * * 4237 GntR family transcriptional regulator, arabinose operon transcriptional repressor CAETHG_2232 * * 4238 hypothetical protein CAETHG_2238 * * 4239 hypothetical protein CAETHG_2280 * * 4240 spore coat protein of the CotS family CAETHG_2303 * * 4241 hypothetical protein CAETHG_2305 * * 4242 spore coat protein CAETHG_2307 * * 4243 hypothetical protein CAETHG_2361 * * 4244 hypothetical protein CAETHG_2371 * * 4245 Transposase CAETHG_2386 * * 4246 benzoate transporter membrane protein CAETHG_2388 * *

- 121 044153

4247 nicotinate nucleotide pyrophosphorylase (carboxylating) 2.4.2.19 CAETHG_2389 * * 4248 synthesis domain-containing protein molybdenum cofactor CAETHG_2390 * * 4249 2-keto-4-pentenoate hydratase CAETHG_2391 * * 4250 protein containing a BFD-like [2Fe-2S]binding domain CAETHG_2392 * * 4251 hypothetical protein CAETHG_2393 * * 4252 Protein of unknown function (DUF111) CAETHG_2394 * * 4253 hypothetical protein CAETHG_2395 * * 4254 IcIR family transcriptional regulator CAETHG_2396 * * 4255 uncharacterized protein CAETHG_2397 * * 4256 4-hydroxytetrahydrodipicolinate synthase 4.2.1.52 CAETHG_2398 * * 4257 Sensor module with four-helical bundle motif for signal transmission CAETHG_2399 * * 4258 methyl acceptor chemotaxis protein CAETHG_2400 * * 4259 Pyruvate kinase, barrel domain CAETHG_2440 * * 4260 protein containing collagen triple helix repeat CAETHG_2494 * * 4261 carbamoylphosphate synthase, small subunit CAETHG_2509 * * 4262 hypothetical protein CAETHG_2526 * * 4263 ABC transport system, proposed ATP binding protein CAETHG_2559 * * 4264 ABC transport system, putative permease protein CAETHG_2560 * * 4265 glycosyltransferase CAETHG_2600 * * 4266 hypothetical protein CAETHG_2601 * * 4267 membrane protein O-antigen ligase-like CAETHG_2603 * * 4268 hypothetical protein CAETHG_2605 * * 4269 GT2 family glycosyltransferase CAETHG_2606 * * 4270 transferase hexapeptide (protein containing six repeats) CAETHG_2607 * * 4271 Membrane protein involved in the export of O-antigen and teichoic acid CAETHG_2610 * * 4272 Glycosyltransferase involved in cell wall bisynthesis CAETHG_2611 * * 4273 hypothetical protein CAETHG_2612 * * 4274 Glycosyltransferase involved in cell wall bisynthesis CAETHG_2613 * * 4275 hypothetical protein CAETHG_2614 * * 4276 glycosyltransferase CAETHG_2624 * * 4277 hypothetical protein CAETHG_2648 * * 4278 hypothetical protein CAETHG_2665 * * 4279 hypothetical protein CAETHG_2676 * * 4280 hypothetical protein CAETHG_2686 * * 4281 Protein containing a helix-loop-helix domain CAETHG_2715 * * 4282 hypothetical protein CAETHG_2736 * * 4283 argininosuccinate synthase CAETHG_2760 * * 4284 hypothetical protein CAETHG_2804 * * 4285 selenocysteine-specific factor elongation CAETHG_2841 * * 4286 Sensor module with four-helical bundle motif for signal transmission CAETHG_2857 * *

- 122 044153

4287 16S rRNA(uracil1498-N3)-methyltransferase CAETHG_2895 * * 4288 arginine antiporter:ornithine / lysine permease CAETHG_3023 * * 4289 flaG, flagella protein CAETHG_3050 * * 4290 Family 2 glycosyltransferase CAETHG_3066 * * 4291 Protein containing an AAA-like domain CAETHG_3080 * * 4292 hypothetical protein CAETHG_3169 * * 4293 hypothetical protein CAETHG_3210 * * 4294 hypothetical protein CAETHG_3356 * * 4295 hypothetical protein CAETHG_3366 * * 4296 hypothetical protein CAETHG_3421 * * 4297 5'-phosphate synthase, pdxT subunit CAETHG_3434 * * 4298 Blal family transcription regulator, penicillinase repressor CAETHG_3439 * * 4299 Protein of unknown function (DUF3793) CAETHG_3484 * * 4300 Na+-dependent efflux pump multidrug resistance CAETHG_3501 * * 4301 Uncharacterized conserved protein CAETHG_3517 * * 4302 hypothetical protein CAETHG_3518 * * 4303 hypothetical protein CAETHG_3523 * * 4304 chromosome separation protein CAETHG_3524 * * 4305 hypothetical protein CAETHG_3527 * * 4306 Uncharacterized conserved protein CAETHG_3529 * * 4307 hypothetical protein CAETHG_3530 * * 4308 protein HxsD of the His-Xaa-Ser system CAETHG_3531 * * 4309 protein HxsD of the His-Xaa-Ser system CAETHG_3532 * * 4310 hypothetical protein CAETHG_3533 * * 4311 type IV leader peptidase family protein CAETHG_3534 * * 4312 hypothetical protein CAETHG_3535 * * 4313 maturase HxsC of the His-Xaa-Ser system containing the SAM radical CAETHG_3536 * * 4314 maturase HxsB of the His-Xaa-Ser system containing the SAM radical CAETHG_3537 * * 4315 hypothetical protein CAETHG_3539 * * 4316 hypothetical protein CAETHG_3540 * * 4317 protein containing the SAM radical and an additional 4Fe4S binding domain SPASM CAETHG_3541 * * 4318 Resolvase, N terminal domain CAETHG_3550 * * 4319 Phage protein-related protein CAETHG_3551 * * 4320 Helix-loop-helix domain CAETHG_3552 * * 4321 Diadenosine tetraphosphate-(Ar4A)-hydrolase CAETHG_3556 * * 4322 ATP-dependent helicase IRC3 CAETHG_3557 * * 4323 Predicted non-canonical NTP pyrophosphatase housecleaning all-alpha NTP PPase superfamily (MazG) CAETHG_3558 * * 4324 AAA domain-containing protein (dynein-related protein subfamily) CAETHG_3559 * * 4325 hypothetical protein CAETHG_3560 * * 4326 hypothetical protein CAETHG_3561 * * 4327 immunity protein Imm6 CAETHG_3562 * * 4328 Protein containing a helix-loop-helix domain CAETHG_3567 * * 4329 Putative binding protein CAETHG_3577 * *

- 123 044153

cell wall 4330 IcIR family transcriptional regulator CAETHG_3583 * * 4331 Hydroxymethylglutaryl-CoA synthase CAETHG_3584 * * 4332 acetyl-CoA-C-acetyltransferase CAETHG_3585 * * 4333 hypothetical protein CAETHG_3586 * * 4334 Predicted MFS family arabinose efflux permease CAETHG_3587 * * 4335 Predicted MFS family arabinose efflux permease CAETHG_3588 * * 4336 hypothetical protein CAETHG_3589 * * 4337 hypothetical protein CAETHG_3599 * * 4338 hypothetical protein CAETHG_3667 * * 4339 hypothetical protein CAETHG_3687 * * 4340 hypothetical protein CAETHG_3688 * * 4341 tryptophan synthase, alpha chain CAETHG_3708 * * 4342 Spore germination protein CAETHG_3745 * * 4343 hypothetical protein CAETHG_3756 * * 4344 hypothetical protein CAETHG_3758 * * 4345 hypothetical protein CAETHG_3759 * * 4346 IseA DL endopeptidase inhibitor CAETHG_3760 * * 4347 putative transcriptional regulator CAETHG_3761 * * 4348 hypothetical protein CAETHG_3762 * * 4349 hypothetical protein CAETHG_3764 * * 4350 hypothetical protein CAETHG_3765 * * 4351 hypothetical protein CAETHG_3766 * * 4352 RNA-dependent RNA polymerase CAETHG_3767 * * 4353 hypothetical protein CAETHG_3768 * * 4354 ABC exinuclease C domain-containing protein CAETHG_3769 * * 4355 hypothetical protein CAETHG_3770 * * 4356 Protein of unknown function (DUF4236) CAETHG_3771 * * 4357 hypothetical protein CAETHG_3772 * * 4358 hypothetical protein CAETHG_3773, CAETHG_3801 * * 4359 hypothetical protein CAETHG_3774 * * 4360 hypothetical protein CAETHG_3775 * * 4361 hypothetical protein CAETHG_3776 * * 4362 putative phage terminase of the P27 family, small subunit CAETHG_3777 * * 4363 Phage terminase-like protein, large subunit, contains an N-terminal HTH domain CAETHG_3778 * * 4364 hypothetical protein CAETHG_3779 * * 4365 phage portal protein of the HK97 family CAETHG_3780 * * 4366 ATP-dependent protease C1pP, protease subunit CAETHG_3781 * * 4367 main capsid protein of the HK97 family phage CAETHG_3782 * * 4368 uncharacterized phage protein (possibly involved in DNA packaging) CAETHG_3783 * * 4369 protein that connects the phage head and tail CAETHG_3784 * * 4370 Bacteriophage HK97-gplO, putative component of the process CAETHG_3785 * *

- 124 044153

4371 hypothetical protein CAETHG_3786 * * 4372 Phage process coat protein CAETHG_3787 * * 4373 Phage process tube protein CAETHG_3788 * * 4374 hypothetical protein CAETHG_3789 * * 4375 SLT domain-containing protein CAETHG_3790 * * 4376 hypothetical protein CAETHG_3791 * * 4377 NlpC/P60 family protein CAETHG_3792 * * 4378 Protein of unknown function (DUF2577) CAETHG_3793 * * 4379 Protein of unknown function (DUF2634) CAETHG_3794 * * 4380 Uncharacterized phage protein gp47/JayE CAETHG_3795 * * 4381 hypothetical protein (DUF2313) CAETHG_3796 * * 4382 parallel beta-helical repeat (two copies) CAETHG_3797 * * 4383 Hemolysin XhlA CAETHG_3798 * * 4384 Lysozyme Ml (1,4-beta-N-acetylmuramidase) of the GH25 family CAETHG_3799 * * 4385 hypothetical protein CAETHG_3800 * * 4386 RetK-like, MazF-like toxin toxin- antitoxin system type II CAETHG_3802 * * 4387 hypothetical protein CAETHG_3811 * * 4388 extracellular protein that binds solutes CAETHG_3832 * * 4389 hypothetical protein CAETHG_3902 * * 4390 hypothetical protein CAETHG_3973 * * 4391 hypothetical protein CAETHG_3974 * * 4392 Broadly specific NMP kinase CAETHG_3976 * * 4393 Protein containing a methyltransferase domain CAETHG_3977 * * 4394 protein of unknown function (DUF4351) CAETHG_3978 * * 4395 hypothetical protein CAETHG_3986 * * 4396 protein containing collagen triple helix repeat CAETHG_4029 * * 4397 hypothetical protein CAETHG_4052 * * 4398 hypothetical protein * * CLRAG_00050 4399 multidrug protein MdtC resistance * * CLRAG_00060 4400 precursor protein multiple drug resistance MdtA * * CLRAG_00070 4401 protein-regulator of fatty acid metabolism * * CLRAG_00080 4402 right origin of replication binding protein * * CLRAG_00140 4403 hypothetical protein * * CLRAG_00150 4404 hypothetical protein * * CLRAG_00160 4405 hypothetical protein * * CLRAG_00170 4406 xylulose kinase * * CLRAG_00360 4407 nickel binder precursor periplasmic protein * * CLRAG_00400 4408 glutathione-importing ATP-binding protein GsiA * * CLRAG_00410 4409 ATP-binding transport protein OppD oligopeptides * * CLRAG_00420 4410 glutathione transport system, permease protein GsiD * * CLRAG_00430 4411 glutathione transport system, permease * * CLRAG_00440

- 125 044153

GsiC protein 4412 nickel transport system, permease protein NikB * * CLRAG_00450 4413 putative methyltransferase YcgJ * * CLRAG_00460 4414 serine/threonine transporter SstT * * CLRAG_00740 4415 oxygen regulating protein NreC * * CLRAG_00750 4416 putative YdhV oxidoreductase * * CLRAG_00770 4417 cell division inhibitor MinD * * CLRAG_00810 4418 hypothetical protein * * CLRAG_00820 4419 hypothetical protein * * CLRAG_00830 4420 hypothetical protein * * CLRAG_00840 4421 hypothetical protein * * CLRAG_00850 4422 putative ABC transporter, ATP-binding protein YxIF * * CLRAG_00860 4423 hypothetical protein * * CLRAG_01050 4424 demethylrebeccamycin-O-glucose-O-methyltransferase * * CLRAG_01080 4425 hypothetical protein * * CLRAG_01160 4426 putative electron transport protein YccM * * CLRAG_01220 4427 ribonuclease D * * CLRAG_01280 4428 HTN-type transcriptional regulator protein GabR * * CLRAG_01380 4429 hypothetical protein * * CLRAG_01560 4430 CRISPR-associated protein Cas6 * * CLRAG_01570 4431 CRISPR-associated protein (cas_TM1802) * * CLRAG_01580 4432 hypothetical protein * * CLRAG_01590 4433 CRISPR-associated protein (Cas_Cas5) * * CLRAG_01600 4434 CRISPR-associated nuclease/helicase Cas3 * * CLRAG_01610 4435 hypothetical protein * * CLRAG_01620 4436 CRISPR-associated endonuclease Casl * * CLRAG_01630 4437 CRISPR-associated endoribonuclease Cas2 * * CLRAG_01640 4438 hypothetical protein * * CLRAG_01830 4439 uroporphyrinogen decarboxylase * * CLRAG_02060 4440 magnesium chelatase, 38-kDa subunit * * CLRAG_02080 4441 magnesium chelatase, 38-kDa subunit * * CLRAG_02090 4442 Aerobic cobalt chelatase, CobN subunit * * CLRAG_02100 4443 Precursor N-acetylmuramoyl-b alanine amidase LytC * * CLRAG_02110 4444 hemin transport system, permease protein HmuU * * CLRAG_02120 4445 siderophore transport system, putative ATP-binding protein * * CLRAG_02130 4446 vitamin B12 binding protein precursor * * CLRAG_02140 4447 hypothetical protein * * CLRAG_02230 4448 YqaJ-like viral recombinase domain-containing protein * * CLRAG_02240 4449 hypothetical protein * * CLRAG_02250 4450 HTH-type transcriptional regulator ImmR * * CLRAG_02260 4451 hypothetical protein * * CLRAG_02270 4452 hypothetical protein * * CLRAG_02300

- 126 044153

4453 hypothetical protein * * CLRAG_02310 4454 GTP pyrophosphokinase YjbM * * CLRAG_02320 4455 hypothetical protein * * CLRAG_02330 4456 50S ribosomal protein L22/fusion protein with unknown domains * * CLRAG_02340 4457 hypothetical protein * * CLRAG_02350 4458 hypothetical protein * * CLRAG_02360 4459 hypothetical protein * * CLRAG_02370 4460 hypothetical protein * * CLRAG_02380 4461 hypothetical protein * * CLRAG_02390 4462 propanediol utilization protein PduA * * CLRAG_02940 4463 biotin transporter BioY2 * * CLRAG_03060 4464 biotin synthase * * CLRAG_03070 4465 cocaineesterase * * CLRAG_03080 4466 HTH-type transcriptional regulator Bm3Rl * * CLRAG_03090 4467 hypothetical protein * * CLRAG_03100 4468 hypothetical protein * * CLRAG_03110 4469 hypothetical protein * * CLRAG_03150 4470 homoserine/homoserine lactone efflux protein * * CLRAG_03160 4471 HTN-type transcriptional regulator protein GabR * * CLRAG_03170 4472 putative sensor protein YfmS converter * * CLRAG_03180 4473 ferredoxin * * CLRAG_03190 4474 benzylsuccinate synthase, alpha subunit * * CLRAG_03200 4475 hypothetical protein * * CLRAG_03210 4476 hypothetical protein * * CLRAG_03220 4477 hypothetical protein * * CLRAG_03230 4478 hypothetical protein * * CLRAG_03260 4479 putative protein containing peptidoglycan-binding domain * * CLRAG_03270 4480 galactoside-O-acetyltransferase * * CLRAG_03280 4481 putative ribosomal N- acetyltransferase YdaF * * CLRAG_03290 4482 SoxS regulatory protein * * CLRAG_03300 4483 hypothetical protein * * CLRAG_03320 4484 spiral-loop-helix motif * * CLRAG_03380 4485 hypothetical protein * * CLRAG_03410 4486 hypothetical protein * * CLRAG_03420 4487 hypothetical protein * * CLRAG_03430 4488 hypothetical protein * * CLRAG_03440 4489 N-terminal protease CAAX of autoimmunity * * CLRAG_03800 4490 putative ribosomal N- acetyltransferase YdaF * * CLRAG_03860 4491 hypothetical protein * * CLRAG_03940 4492 DNA-binding transcriptional repressor MarR * * CLRAG_03950 4493 flavodoxin * * CLRAG_03960 4494 sensor protein kinase WalK * * CLRAG_04310 4495 transcriptional regulator protein WaIR * * CLRAG_04320 4496 Inner membrane protein YdjZ of the TVP38/TMEM64 family * * CLRAG_04330

- 127 044153

4497 phosphatidylcholine synthase * * CLRAG_04340 4498 Protein A of the potassium absorption system Ktr * * CLRAG_04460 4499 Protein B of the potassium absorption system Ktr * * CLRAG_04470 4500 putative sensor protein YfmS converter * * CLRAG_04500 4501 Precursor N-acetylmuramoyl-E- alanine amidase LytC * * CLRAG_05510 4502 hypothetical protein * * CLRAG_05520 4503 methyl acceptor protein McpA chemotaxis * * CLRAG_05560 4504 nitrogenase, molybdenum-iron-containing protein, alpha chain * * CLRAG_05590 4505 nitrogenase, molybdenum-iron protein, beta chain * * CLRAG_05600 4506 FeMo cofactor biosynthesis protein NifB * * CLRAG_05620 4507 methyl acceptor protein 4 chemotaxis * * CLRAG_05770 4508 FIST N domain-containing protein * * CLRAG_05780 4509 hypothetical protein * * CLRAG_05830 4510 6-aminohexanoate dimer hydrolase * * CLRAG_05890 4511 protein A of the UvrABC system * * CLRAG_05900 4512 Btr HTN-type transcriptional activator * * CLRAG_05910 4513 Protein A carbon starvation * * CLRAG_06580 4514 ATP-binding transport protein OppD oligopeptides * * CLRAG_06890 4515 epoxyqueuosine reductase * * CLRAG_06980 4516 hypothetical protein * * CLRAG_07010 4517 GDSL-like lipase/acyl hydrolase * * CLRAG_07020 4518 3',5'-cyclic adenosine monophosphate phosphodiesterase CpdA * * CLRAG_07200 4519 chromosome segregation protein * * CLRAG_07280 4520 precursor of internalin A * * CLRAG_07290 4521 precursor of internalin A * * CLRAG_07300 4522 hypothetical protein * * CLRAG_07360 4523 HTH-type transcriptional regulator CynR * * CLRAG_08110 4524 hypothetical protein * * CLRAG_08690 4525 protein-transcription regulator PhoP synthesis of alkaline phosphatase * * CLRAG_08810 4526 hypothetical protein * * CLRAG_08840 4527 hypothetical protein * * CLRAG_08850 4528 hypothetical protein * * CLRAG_08860 4529 restriction enzyme R type 1 protein * * CLRAG_08890 4530 protein containing a DNA specificity domain for a type 1 restriction modification enzyme * * CLRAG_08900 4531 putative PM type 1 restriction enzyme protein * * CLRAG_08910 4532 glutamate racemase * * CLRAG_08930 4533 ferredoxin * * CLRAG_08950 4534 methyl-acceptor protein McpC chemotaxis * * CLRAG_08990 4535 N-substituted precursor formamide deformylase * * CLRAG_09020 4536 multidrug resistance export protein MerA * * CLRAG_09030 4537 spore germination protein GerE * * CLRAG_09050 4538 carboxylesterase NlhH * * CLRAG_09110

- 128 044153

4539 hypothetical protein * * CLRAG_09120 4540 hypothetical protein * * CLRAG_09200 4541 multiantibiotic resistance protein MagA * * CLRAG_09210 4542 cyclic di-GMP phosphodiesterase response regulator RpfG * * CLRAG_09300 4543 peroxide response repressor PerR * * CLRAG_09310 4544 putative sensor protein YfmS converter * * CLRAG_09350 4545 copper-sensing repressor CsoR transcription * * CLRAG_09360 4546 putative copper-exporting P-type ATPase V * * CLRAG_09370 4547 DNA-binding transcriptional regulator AgaC * * CLRAG_09380 4548 protein of the alpha/beta hydrolase family * * CLRAG_09390 4549 right origin of replication binding protein * * CLRAG_09400 4550 demethylrebeccamycin-O-glucose-O-methyltransferase * * CLRAG_09410 4551 ATP-binding/iron import permease protein 1 rtA * * CLRAG_09420 4552 putative ATP-binding/multidrug export permease protein * * CLRAG_09430 4553 hypothetical protein * * CLRAG_09490 4554 hypothetical protein * * CLRAG_09610 4555 hypothetical protein * * CLRAG_09620 4556 hypothetical protein * * CLRAG_09630 4557 chromosome separation protein Smc * * CLRAG_09640 4558 hypothetical protein * * CLRAG_09700 4559 phosphoadenosine phosphosulfate reductase * * CLRAG_09760 4560 hypothetical protein * * CLRAG_09770 4561 hypothetical protein * * CLRAG_09780 4562 hypothetical protein * * CLRAG_09790 4563 cysteine desulfurase SufS * * CLRAG_09800 4564 type III restriction enzyme, res subunit * * CLRAG_09810 4565 hypothetical protein * * CLRAG_09820 4566 chromosome separation protein Smc * * CLRAG_09830 4567 hypothetical protein * * CLRAG_09840 4568 sigma factor RpoS RNA polymerase * * CLRAG_09850 4569 endonuclease/exonuclease/phosphatase family protein * * CLRAG_09880 4570 hypothetical protein * * CLRAG_09890 4571 protein similar to plasmid protein pRiA4b 0RF-3 * * CLRAG_09900 4572 hypothetical protein * * CLRAG_09930 4573 hydroperoxyfatty acid reductase gpxl * * CLRAG_10140 4574 transcriptional regulator of organic hydroperoxide resistance * * CLRAG_10150 4575 alanine tRNA ligase * * CLRAG_10160 4576 hypothetical protein * * CLRAG_10960 4577 hypothetical protein * * CLRAG_11060 4578 replication-associated recombination protein A * * CLRAG_11710 4579 putative multidrug resistance protein EmrK * * CLRAG_12840

- 129 044153

4580 hypothetical protein * * CLRAG_13370 4581 hypothetical protein * * CLRAG_13390 4582 hypothetical protein * * CLRAG_13400 4583 hypothetical protein * * CLRAG_13420 4584 glycosyltransferase SunS derived from prophage SPBc2 * * CLRAG_13430 4585 hypothetical protein * * CLRAG_13440 4586 hypothetical protein * * CLRAG_13450 4587 flagellin * * CLRAG_13460 4588 hypothetical protein * * CLRAG_13490 4589 Flagellar hook associated protein FlgL * * CLRAG_13580 4590 Precursor N-acetylmuramoyl-E- alanine amidase LytC * * CLRAG_13940 4591 ABC transporter, YxdM permease protein * * CLRAG_14390 4592 sensor histidine kinase GraS * * CLRAG_14410 4593 glyoxylate/hydroxypyruvate reductase A * * CLRAG_14820 4594 sugar phosphatase YidA * * CLRAG_14920 4595 phosphomethylpyrimidine synthase * * CLRAG_15080 4596 predecessor amidophosphoribosyltransferases * * CLRAG_15090 4597 predecessor amidophosphoribosyltransferases * * CLRAG_15100 4598 hypothetical protein * * CLRAG_15150 4599 isoprenyltransferase * * CLRAG_15210 4600 putative sugar kinase YdjH * * CLRAG_15530 4601 permease of cytosine/purines, uracil, thiamine, allantoin * * CLRAG_15540 4602 ADP-ribosylphosphohydrolase * * CLRAG_15550 4603 putative HTH-type transcriptional regulator YurK * * CLRAG_15560 4604 ATP-binding region * * CLRAG_15700 4605 hypothetical protein * * CLRAG_15750 4606 ethanolamine ammonia lyase reactivating factor * * CLRAG_15830 4607 formamidase * * CLRAG_15860 4608 Low affinity putrescine importer P1aP * * CLRAG_15870 4609 hypothetical protein * * CLRAG_15890 4610 acetoacetate decarboxylase (ADC) * * CLRAG_15900 4611 putative diguanylate cyclase YedQ * * CLRAG_15960 4612 putative thiazole biosynthetic enzyme * * CLRAG_15990 4613 YdjP protein of the AB hydrolase superfamily * * CLRAG_16030 4614 putrescine importer PuuP * * CLRAG_16040 4615 hypothetical protein * * CLRAG_16090 4616 Chagasin family peptidase inhibitor 142 * * CLRAG_16320 4617 hypothetical protein * * CLRAG_16330 4618 hypothetical protein * * CLRAG_16340 4619 hypothetical protein * * CLRAG_16360 4620 putative glycosyltransferase * * CLRAG_16400 4621 methyl acceptor protein 4 chemotaxis * * CLRAG_16630 4622 outer membrane protein assembly factor Bate * * CLRAG_16660 4623 hypothetical protein * * CLRAG_16690

- 130 044153

4624 hypothetical protein * * CLRAG_16700 4625 hypothetical protein * * CLRAG_16710 4626 hypothetical protein * * CLRAG_16720 4627 hypothetical protein * * CLRAG_16730 4628 tyrosine recombinase XerD * * CLRAG_16760 4629 tyrosine recombinase HegC * * CLRAG_16770 4630 tyrosine recombinase XerD * * CLRAG_16780 4631 chaperone protein DnaJ * * CLRAG_16810 4632 tetratricopeptide repeat-containing protein * * CLRAG_16820 4633 chaperone protein DnaK * * CLRAG_16830 4634 GrpE protein * * CLRAG_16840 4635 hypothetical protein * * CLRAG_16850 4636 hypothetical protein * * CLRAG_16860 4637 hypothetical protein * * CLRAG_16870 4638 hypothetical protein * * CLRAG_16890 4639 hypothetical protein * * CLRAG_16900 4640 hypothetical protein * * CLRAG_16910 4641 GTPase Der * * CLRAG_16920 4642 hypothetical protein * * CLRAG_16930 4643 putative diguanylate cyclase YdaM * * CLRAG_16940 4644 putative diguanylate cyclase YdaM * * CLRAG_16950 4645 multidrug protein stability Stp * * CLRAG_16960 4646 protein containing a nuclease-related domain * * CLRAG_16970 4647 hypothetical protein * * CLRAG_16990 4648 hypothetical protein * * CLRAG_17010 4649 hypothetical protein * * CLRAG_17020 4650 hypothetical protein * * CLRAG_17040 4651 hypothetical protein * * CLRAG_17050 4652 HTH-type mta transcription activator * * CLRAG_17100 4653 hypothetical protein * * CLRAG_17290 4654 hypothetical protein * * CLRAG_17960 4655 putative methyltransferase YcgJ * * CLRAG_18120 4656 putative xantidehydrogenase, subunit A * * CLRAG_18190 4657 FmdE, molybdenumformylmethanofurandehydrogenase operon * * CLRAG_18200 4658 hypothetical protein * * CLRAG_18210 4659 vitamin B12 binding protein * * CLRAG_18220 4660 5-adenosyl-E-methionine binding protein * * CLRAG_18230 4661 molybdopterinmolybdenumtransferase * * CLRAG_18240 4662 molybdate transporter, ATP-binding protein * * CLRAG_18250 4663 hypothetical protein * * CLRAG_18270 4664 protein acetyltransferase family (GNAT) * * CLRAG_18290 4665 hypothetical protein * * CLRAG_18300 4666 hypothetical protein * * CLRAG_18310 4667 HTH-type transcriptional regulator GltR * * CLRAG_18330 4668 putative NAD(P)H-dependent FMN-containing * * CLRAG_18340

- 131 044153

YwqN oxidoreductase 4669 flavodoxin * * CLRAG_18350 4670 hypothetical protein * * CLRAG_18360 4671 1-deoxy-O-xylulose-5-phosphate synthase * * CLRAG_18640 4672 3-oxoacyl-[acyl carrier protein group]-reductase FabG * * CLRAG_18650 4673 putative tartrate transporter * * CLRAG_18660 4674 hypothetical protein * * CLRAG_18970 4675 hypothetical protein * * CLRAG_19420 4676 methionine synthase * * CLRAG_19430 4677 hypothetical protein * * CLRAG_19450 4678 penicillinase repressor * * CLRAG_19480 4679 regulatory protein BlaRl * * CLRAG_19490 4680 protein family isoprenylcysteine carboxyl methyltransferase (ICMT) * * CLRAG_20000 4681 hypothetical protein * * CLRAG_20110 4682 hypothetical protein * * CLRAG_20340 4683 hypothetical protein * * CLRAG_20360 4684 Precursor N-acetylmuramoyl-E- alanine amidase LytC * * CLRAG_20370 4685 hypothetical protein * * CLRAG_20420 4686 protein TetD transposon TpY * * CLRAG_20430 4687 ankyrin repeats (3 copies) * * CLRAG_20500 4688 hypothetical protein * * CLRAG_20510 4689 putative multidrug resistance protein EmrY * * CLRAG_20520 4690 hypothetical protein * * CLRAG_20910 4691 transcription regulator protein of the CsgBAC operon * * CLRAG_20920 4692 M28 peptidase family protein * * CLRAG_20930 4693 putative penicillin-binding PbpX protein * * CLRAG_20980 4694 HTN-type RhaR transcriptional activator * * CLRAG_21010 4695 RsxB subunit of the electron transport complex * * CLRAG_21020 4696 hypothetical protein * * CLRAG_21030 4697 hypothetical protein * * CLRAG_21080 4698 hypothetical protein * * CLRAG_21220 4699 YkvP spore protein * * CLRAG_21370 4700 deacetylase precursor peptidoglycan-N- acetylmuramic acid PdaA * * CLRAG_21380 4701 YkvP spore protein * * CLRAG_21390 4702 hypothetical protein * * CLRAG_21410 4703 hypothetical protein * * CLRAG_21420 4704 putative sulfoacetate transporter SauU * * CLRAG_21570 4705 hypothetical protein * * CLRAG_21770 4706 triosephosphate isomerase * * CLRAG_21830 4707 hypothetical protein * * CLRAG_21840 4708 putative glucarate transporter * * CLRAG_21850 4709 putative sugar phosphate isomerase YwlF * * CLRAG_21870 4710 HTH-type GlcR transcriptional repressor * * CLRAG_21890

- 132044153

4711 cyclic synthase pyranopterin monophosphate * * CLRAG_22260 4712 4-Hydroxyphenylacetate decarboxylase, large subunit * * CLRAG_22270 4713 enzyme that activates 4- hydroxyphenylacetate decarboxylase * * CLRAG_22280 4714 methyl acceptor chemotaxis protein 3 * * CLRAG_22290 4715 hypothetical protein * * CLRAG_22300 4716 protein containing a nuclease-related domain * * CLRAG_22310 4717 AAA divergent domain protein * * CLRAG_22380 4718 HTH-type transcriptional regulator AcrR * * CLRAG_22390 4719 multidrug protein sustainability 3 * * CLRAG_22400 4720 hypothetical protein * * CLRAG_22410 4721 hypothetical protein * * CLRAG_22420 4722 ferredoxin * * CLRAG_22430 4723 hypothetical protein * * CLRAG_22460 4724 hypothetical protein * * CLRAG_22470 4725 hypothetical protein * * CLRAG_22480 4726 hypothetical protein * * CLRAG_22490 4727 hypothetical protein * * CLRAG_22500 4728 hypothetical protein * * CLRAG_22510 4729 Haell modification methylase * * CLRAG_22520 4730 hypothetical protein * * CLRAG_22530 4731 hypothetical protein * * CLRAG_22540 4732 sensor protein FixL * * CLRAG_22550 4733 hypothetical protein * * CLRAG_22560 4734 hypothetical protein * * CLRAG_22570 4735 transposition protein TnsC transposon Tn7 * * CLRAG_22580 4736 transposition protein TnsB transposon Tn7 * * CLRAG_22590 4737 transposition protein TnsA transposon Tn7 * * CLRAG_22600 4738 small subunit ribosomal RNA methyltransferase A * * CLRAG_23630 4739 hypothetical protein * * CLRAG_23650 4740 hypothetical protein * * CLRAG_23660 4741 hypothetical protein * * CLRAG_23670 4742 hypothetical protein * * CLRAG_23680 4743 hypothetical protein * * CLRAG_23740 4744 anaerobic transcriptional regulator of benzoate catabolism * * CLRAG_23750 4745 hypothetical protein * * CLRAG_23760 4746 hypothetical protein * * CLRAG_23770 4747 hypothetical protein * * CLRAG_23780 4748 HNH endonuclease * * CLRAG_23790 4749 hypothetical protein * * CLRAG_23800 4750 hypothetical protein * * CLRAG_23810 4751 DNA replication and repair protein RecF * * CLRAG_23820 4752 hypothetical protein * * CLRAG_23830 4753 hypothetical protein * * CLRAG_23860 4754 serine/threonine protein kinase PrkC * * CLRAG_23870

- 133 044153

4755 hypothetical protein * * CLRAG_23880 4756 galactoside-O-acetyltransferase * * CLRAG_23890 4757 hypothetical protein * * CLRAG_23900 4758 Transcription activator of the Hca operon * * CLRAG_23910 4759 NADH oxidase * * CLRAG_23920 4760 demethylmenaquinone methyltransferase * * CLRAG_23970 4761 hypothetical protein * * CLRAG_24030 4762 hypothetical protein * * CLRAG_24240 4763 hypothetical protein * * CLRAG_24250 4764 hypothetical protein * * CLRAG_24260 4765 N-terminal protease CAAX of autoimmunity * * CLRAG_24400 4766 outer membrane protein assembly factor BamD * * CLRAG_24860 4767 putative protein binding to cell wall and containing repeat 2 * * CLRAG_24870 4768 hypothetical protein * * CLRAG_25030 4769 altronate dehydratase * * CLRAG_25040 4770 2-keto-3-deoxygluconate permease * * CLRAG_25050 4771 2-dehydro-3-deoxygluconokinase * * CLRAG_25060 4772 transcription regulator KdgR * * CLRAG_25080 4773 methyl acceptor protein 4 chemotaxis * * CLRAG_25200 4774 ammonium transporter NrgA * * CLRAG_25480 4775 ribosomal protein 55-alanine-N- acetyltransferase * * CLRAG_26200 4776 protein acetyltransferase family (GNAT) * * CLRAG_26210 4777 hypothetical protein * * CLRAG_26230 4778 efflux transporter regulator multidrug 1 * * CLRAG_26240 4779 putative YdeA protease * * CLRAG_26400 4780 Precursor N-acetylmuramoyl-1- alanine amidase LytC * * CLRAG_26410 4781 putative transposase * * CLRAG_26740 4782 hypothetical protein * * CLRAG_26800 4783 tyrosine recombinase HegC * * CLRAG_26810 4784 tyrosine recombinase XerD * * CLRAG_26820 4785 hypothetical protein * * CLRAG_27210 4786 hypothetical protein * * CLRAG_27610 4787 diacylglycerol kinase * * CLRAG_28550 4788 sodium/glucose co-transporter * * CLRAG_28930 4789 3-oxoacyl-[acyl carrier protein group]-reductase FabG * * CLRAG_28940 4790 Protein containing a BNR/Asp box repeat * * CLRAG_28950 4791 TaLA protein of the biofilm toxin-antitoxin system * * CLRAG_28960 4792 inner membrane transport protein YajR * * CLRAG_28970 4793 Precursor N-acetylmuramoyl-E- alanine amidase LytC * * CLRAG_28990 4794 hypothetical protein * * CLRAG_29010 4795 staygreen protein * * CLRAG_29020 4796 methyl-acceptor protein McpC chemotaxis * * CLRAG_29070 4797 protein R-N, regulating nitrogen metabolism * * CLRAG_29090

- 134 044153

4798 hypothetical protein * * CLRAG_29100 4799 Ammonium channel precursor * * CLRAG_29110 4800 chemotaxis protein CheY * * CLRAG_29140 4801 CheY-P-phosphatase CheC * * CLRAG_29150 4802 Cyclic di-GMP phosphodiesterase Gmr * * CLRAG_29160 4803 hypothetical protein * * CLRAG_29340 4804 hypothetical protein * * CLRAG_29390 4805 chaperone protein C1pB * * CLRAG_29400 4806 hypothetical protein * * CLRAG_29410 4807 hypothetical protein * * CLRAG_29420 4808 hypothetical protein * * CLRAG_29430 4809 hypothetical protein * * CLRAG_29440 4810 transcription regulator protein ZraR * * CLRAG_29480 4811 YvrJ family protein * * CLRAG_29810 4812 hypothetical protein * * CLRAG_29880 4813 hypothetical protein * * CLRAG_29900 4814 hypothetical protein * * CLRAG_29910 4815 hypothetical protein * * CLRAG_29920 4816 chaperone protein C1pB * * CLRAG_29930 4817 hypothetical protein * * CLRAG_29940 4818 C-methyltransferase UbiE for ubiquinone/menaquinone biosynthesis * * CLRAG_29950 4819 heme response regulator HssR * * CLRAG_29960 4820 alkaline phosphatase synthesis sensor protein PhoR * * CLRAG_29970 4821 purine efflux pump PbuE * * CLRAG_29980 4822 transposase * * CLRAG_30020 4823 N-acylhomoserine lactonase * * CLRAG_30030 4824 aldehyde oxidoreductase * * CLRAG_30550 4825 Na(+)-translocating subunit F of NADH-quinone reductase * * CLRAG_30670 4826 hypothetical protein * * CLRAG_30720 4827 inner membrane protein YdgC * * CLRAG_30750 4828 pseudouridine synthase A of the small ribosomal subunit * * CLRAG_31120 4829 hypothetical protein * * CLRAG_31130 4830 LysM domain-containing protein * * CLRAG_31150 4831 gluconate 5-dehydrogenase * * CLRAG_31660 4832 glutamate methylesterase-chemotaxis reaction regulator * * CLRAG_31670 4833 hypothetical protein * * CLRAG_31950 4834 bacterial IgG-like domain (group 2) * * CLRAG_31970 4835 hypothetical protein * * CLRAG_31980 4836 bacterial IgG-like domain (group 2) * * CLRAG_32030 4837 hypothetical protein * * CLRAG_32190 4838 hypothetical protein * * CLRAG_32360 4839 hypothetical protein * * CLRAG_32440 4840 hypothetical protein * * CLRAG_32450 4841 recombination and repair protein RecT * * CLRAG_32460 4842 hypothetical protein * * CLRAG_32490 4843 formate dehydrogenase H * * CLRAG_32520

- 135 044153

4844 hypothetical protein * * CLRAG_32740 4845 hypothetical protein * * CLRAG_32950 4846 hypothetical protein * * CLRAG_33250 4847 hypothetical protein * * CLRAG_33300 4848 hypothetical protein * * CLRAG_33320 4849 tyrosine recombinase HegC * * CLRAG_33370 4850 hypothetical protein * * CLRAG_33380 4851 hypothetical protein * * CLRAG_33430 4852 hypothetical protein * * CLRAG_33450 4853 hypothetical protein * * CLRAG_33460 4854 spiral-loop-helix motif * * CLRAG_33470 4855 hypothetical protein * * CLRAG_33480 4856 hypothetical protein * * CLRAG_33520 4857 hypothetical protein * * CLRAG_33550 4858 hypothetical protein * * CLRAG_33570 4859 hypothetical protein * * CLRAG_33610 4860 hypothetical protein * * CLRAG_33620 4861 hypothetical protein * * CLRAG_33630 4862 Helicase containing a DEAD/DEAH box * * CLRAG_33640 4863 hypothetical protein * * CLRAG_33650 4864 hypothetical protein * * CLRAG_33660 4865 hypothetical protein * * CLRAG_33670 4866 hypothetical protein * * CLRAG_33680 4867 hypothetical protein * * CLRAG_33690 4868 DNA methylase N-6 * * CLRAG_33700 4869 hypothetical protein * * CLRAG_33710 4870 hypothetical protein * * CLRAG_33730 4871 hypothetical protein * * CLRAG_33740 4872 hypothetical protein * * CLRAG_33750 4873 hypothetical protein * * CLRAG_33760 4874 DNA invertase hin * * CLRAG_33770 4875 hypothetical protein * * CLRAG_33780 4876 hypothetical protein * * CLRAG_33790 4877 outer membrane protein assembly factor BamD * * CLRAG_33800 4878 tetratricopeptide repeat-containing protein * * CLRAG_33810 4879 hypothetical protein * * CLRAG_33830 4880 intron-encoded protein LtrA group II * * CLRAG_33840 4881 IS200 transposase-like protein * * CLRAG_33850 4882 hypothetical protein * * CLRAG_33920 4883 bacterial IgG-like domain (group 2) * * CLRAG_34030 4884 hypothetical protein * * CLRAG_34040 4885 hypothetical protein * * CLRAG_34050 4886 hypothetical protein * * CLRAG_34060 4887 hypothetical protein * * CLRAG_34070 4888 putative ATP-binding HMP/thiamine import protein YkoD * * CLRAG_34080 4889 carrier of energy metabolism coupling factor, * * CLRAG_34090

- 136 044153

ATP binding protein EcfA2 4890 energy metabolism coupling factor transporter, transmembrane protein EcfT * * CLRAG_34100 4891 protein containing molybdopterin-binding domain oxidoreductase * * CLRAG_34110 4892 hypothetical protein * * CLRAG_34120 4893 intercellular adhesion domain-containing protein * * CLRAG_34130 4894 kappa carrageenase precursor * * CLRAG_34140 4895 hypothetical protein * * CLRAG_34150 4896 3',5'-cyclic adenosine monophosphate phosphodiesterase CpdA * * CLRAG_34160 4897 hypothetical protein * * CLRAG_34170 4898 NHL repeat containing protein * * CLRAG_34180 4899 Precursor N-acetylmypamoyl-L- alanine amidase LytC * * CLRAG_34190 4900 IS2 transposase TprB * * CLRAG_34250 4901 transposase * * CLRAG_34260 4902 transposase * * CLRAG_34270 4903 formate dehydrogenase H * * CLRAG_34290 4904 hypothetical protein * * CLRAG_34320 4905 hypothetical protein * * CLRAG_34330 4906 hypothetical protein * * CLRAG_34340 4907 hypothetical protein * * CLRAG_35240 4908 hypothetical protein * * CLRAG_35800 4909 carboxylesterase NlhH * * CLRAG_35840 4910 group II intron, maturase-specific region * * CLRAG_36010 4911 EcoKI type 1 restriction enzyme specific protein * * CLRAG_36030 4912 hypothetical protein * * CLRAG_36070 4913 protein acetyltransferase family (GNAT) * * CLRAG_36080 4914 hypothetical protein * * CLRAG_36160 4915 hypothetical protein * * CLRAG_36170 4916 type III restriction enzyme, res subunit * * CLRAG_36180 4917 RecBCD enzyme, RecD subunit * * CLRAG_36190 4918 phage integrase family protein * * CLRAG_36200 4919 FRG domain-containing protein * * CLRAG_36210 4920 serine/threonine exchanger SteT * * CLRAG_36480 4921 hypothetical protein * * CLRAG_36660 4922 hypothetical protein * * CLRAG_37100 4923 putative metal-containing chaperone YciC * * CLRAG_37520 4924 protein acetyltransferase family (GNAT) * * CLRAG_37540 4925 Chagasin family peptidase inhibitor 142 * * CLRAG_37550 4926 hypothetical protein * * CLRAG_37560 4927 hypothetical protein * * CLRAG_37580 4928 hypothetical protein * * CLRAG_37590 4929 hypothetical protein * * CLRAG_37600 4930 hypothetical protein * * CLRAG_37630 4931 hypothetical protein * * CLRAG_37900 4932 Precursor N-acetylmypamoyl-L- * * CLRAG_38010

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alanine amidase LytC 4933 precursor of internalin B * * CLRAG_38020 4934 putative YhgA-like transposase * * CLRAG_38240 4935 GDP-mannose-4,6-dehydratase * * CLRAG_38610 4936 GDP-1_fucose synthase * * CLRAG_38620 4937 supposed N- acetylmannosaminyltransferase * * CLRAG_38630 4938 galactoside O-acetyltransferase * * CLRAG_38640 4939 spore coat protein SA * * CLRAG_38650 4940 hypothetical protein * * CLRAG_38660 4941 hypothetical protein * * CLRAG_38670 4942 D-inositol-3-phosphate glycosyltransferase * * CLRAG_38680 4943 putative glycosyltransferase * * CLRAG_38690 4944 hypothetical protein * * CLRAG_38700 4945 hypothetical protein * * CLRAG_38710 4946 glycosyltransferase family protein 11 * * CLRAG_38720 4947 polysaccharide biosynthesis protein * * CLRAG_38730 4948 UDP-glucose-6-dehydrogenase YwqF * * CLRAG_38740 4949 UDP-glucose-4-epimerase * * CLRAG_38760 4950 acyltransferase family protein * * CLRAG_38770 4951 hypothetical protein * * CLRAG_38790 4952 putative acetyltransferase * * CLRAG_38800 4953 hypothetical protein * * CLRAG_38810 4954 acyltransferase family protein * * CLRAG_38820 4955 hypothetical protein * * CLRAG_38850 4956 hypothetical protein * * CLRAG_38860 4957 hypothetical protein * * CLRAG_39020 4958 p-aminobenzoylglutamate hydrolase, subunit B * * CLRAG_39040 4959 sensor histidine kinase YycG * * CLRAG_39300 4960 ABC-2 family transport protein * * CLRAG_39320 4961 ABC-2 family transport protein * * CLRAG_39330 4962 epo x queuosine reductase * * CLRAG_3935O 4963 ATP-dependent RNA helicase RhIE * * CLRAG_39540 4964 hypothetical protein * * CLRAG_39580 4965 CysL HTH-type transcriptional regulator * * CLRAG_39800 4966 molybdenum pterin binding protein MorA * * CLRAG_39810 4967 methionine gamma lyase * * CLRAG_39890 4968 putative transposase DNA-binding domain-containing protein * * CLRAG_39910 4969 putative transposase * * CLRAG_39920 4970 protein containing a helix-loop-helix domain * * CLRAG_39930 4971 ferrous iron transporter protein B * * CLRAG_39960 4972 FeoA domain-containing protein * * CLRAG_39970 4973 hypothetical protein * * CLRAG_39990 4974 hypothetical protein * * CLRAG_40000 4975 hypothetical protein * * CLRAG_40H0 4976 putative glycosyltransferase * * CLRAG_40180

The inventors also identified key metabolic pathways and nodes in Wood-Liu Ngdal microorganisms (figure). The present invention further provides microorganisms with disrupted genes to strategically divert carbon flow away from unnecessary or unwanted metabolic sites through targeted metabolic sites. Such strains have made it possible to improve the production of products obtained at stages subsequent to these targeted metabolic nodes.

Finally, the present invention provides methods for producing products by cultivating a microorganism according to the present invention in the presence of a substrate, for example, a gaseous substrate containing one or more of CO, CO ₂ and/or H ₂ . Possible combinations of disrupted genes to optimize the production of specific products are described in Examples 2-19.

As described elsewhere in this application, such products may include native or non-native products of Wood-Ljungdahl microorganisms. For example, such products include acetyl CoA, ethanol, acetate, butanol, butyrate, butyryl-CoA, 2,3-butanediol, lactate, butene, butadiene, methyl ethyl ketone, ethylene, acetone, isopropanol, lipids, 3-hydroxypropionate (3-HP), isoprene, farnesene, fatty

- 138 044153 acids (ethyl esters of fatty acids, butyl esters of fatty acids), 2-butanol, 1,2propanediol, 1-propanol, chorismate derivative products, 3-hydroxybutyrate, 1,3-butanediol, C ₆ -C ₈ alcohols ( hexanol, heptanol, octanol), caproate, octanoate, isopentenyl pyrophosphate (IPP), dimethylallyl pyrophosphate (DMAPP), acetoacetyl-CoA, 3-hydroxybutyrate-CoA (3-HB-CoA), malonyl-CoA, pyruvate, dehydroshikimate, chorismate, para- hydroxybenzoic acid, salicylate, 2-aminobenzoate, 2,3dihydroxybenzoate, 2-hydroxycyclohexanecarboxylic acid, citramalate, ketobutyrate, acetolactate, acetoin, valine, leucine and isoleucine.

Examples

The following examples further illustrate the present invention, but, of course, should in no way be construed as limiting its essence.

Example 1.

This example describes metabolic modeling in Wood-Ljungdahl microorganisms.

A genome-scale model of Clostridium autoethanogenum metabolism was used, similar to the model described in Marcellin, Green Chem, 18: 3020-3028, 2016. This model was used to simulate the design, engineering, in silico growth and screening of strains with mutations causing gene disruption, for the purpose of predictive identification of strains that will be characterized by an increased yield of native compounds. In addition, new genome-scale models were constructed for a number of strains producing non-native compounds. To do this, heterologous genes and metabolic reactions representing the inclusion of a pathway for producing a non-native compound were added to the structure of the wild-type Clostridium autoethanogenum model. Although the model used for the experimental work described herein is based on Clostridium autoethanogenum, the results obtained can be expected to be applicable to other WoodLjungdahl microorganisms given the similarities in their metabolism.

For each strain, millions of mutant strains containing different combinations of gene disrupting mutations were constructed in silico to produce a chemical compound. Boolean gene-protein-reaction associations have been used to identify inactivated metabolic reactions when a gene is disrupted (Thiele, Nature Protocols, 5: 93-121, 2010). Design, construction and screening of mutant strains were performed using cameo version 0.11.2 (Sonnenschein, Biosustain/Cameo: 0.11.0, doi: doi:10.5281/zenodo.835730, 2017) and evolutionary algorithms implemented using inspyred version 1.0.1 .

The growth of these mutant strains was modeled using two constraint-based computer modeling methods: flux balance analysis (FBA) and linear minimization of metabolic adjustment (LMOMA). These growth modeling techniques were used to identify two plausible metabolic phenotypes following genetic disruption (Maia, Proceedings of the Genetic and Evolutionary Computation Conference Companion on - GECCO '17, New York, New York, ACM Press, 16611668, 2017). An experimental metabolic flux profile was constructed and used as a reference state for LMOMA simulations. Growth simulations were performed using the software scripts cobrapy version 0.8.2 (Ebrahim., COBRApy: COnstraints-Based Reconstruction and Analysis for Python, BMC Syst Biol, 7: 74, 2013), optlang version 1.2.3 ((Jensen, Optlang: An Algebraic Modeling Language for Mathematical Optimization, The Journal of Open Source Software, 2, doi:10.21105/joss.00139, 2017) as a solution search interface and Gurobi Optimizer version 7.0.2 as an optimization solution search tool.

Growth rates and major metabolic fluxes, including fermentation products, were recorded and used for strain screening. Biomass-product coupled yield (BPCY) and molar carbon yield were calculated for each strain simulation. These yield values were used to determine the compliance score.

In addition, flux variability analysis (FVA) was performed to determine whether the mutant strain required production of a compound of interest for growth (growth strain engineering). If the minimum flux of a compound of interest was greater than zero during growth, the strain was classified as growth-coupled. These growth-coupled strain designs should provide increased fermentation stability during continuous fermentation. This minimum flux was converted to carbon yield (minimum FVA yield) and used to compare the level of coupling with growth between strains.

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Example 2.

This example describes disturbances to improve acetate production in WoodLjungdahl microorganisms. Metabolic modeling experiments were performed as described in Example 1. Acetate is a native product of Wood-Ljungdahl microorganisms._____________________

ft Methodology Number of violated Disturbed genes Disturbed reactions as O: 1 η ^S ί > th ί7 aS h 5 ^φ ω ί 3 T Go φ -0 SP with x 9 With; go n S ^χ With; as o ω go o o neck 1 LMOMA output 6 CAETHG_1371, CAETHG_2721, CAETHG_2753, CAETHG_2754, CAETHG_3293, CAETHG_O9O9 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine), phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), homocysteine synthase (0- acetylhomoserine sulfhydrolase (H2S + O-acetyl-Lhomoserine -> acetate + H+ + homocysteine), cysteine desulfhydrase (H2O + L-cysteine <=> NH3 + pyruvate + H2S), prephenate: NAD+ oxidoreductase (decarboxylating) (NAD + prephenate -> NADH + CO2 + phydroxyphenylpyruvate) 0.327282 0.093692 2 LMOMA output 5 CAETHG_1371, CAETHG_2721, CAETHG_2753, CAETHG_2754, CAETHG_3293 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine), phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), homocysteine synthase (0- acetylhomoserine sulfhydrolase) (H2S + O-acetyl-Lhomoserine -> acetate + H+ + homocysteine), cysteine desulfhydrase (H2O + L-cysteine <=> NH3 + pyruvate + H2S) 0.327819 0.093362 3 LMOMA output 6 CAETHG_1371, CAETHG_2721, CAETHG_2751, CAETHG_2753, CAETHG_3293, CAETHG_O9O9 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine), phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ --> ADP + CO2 + phosphoenolpyruvate), citramalate synthase (H2O + pyruvate + acetyl-CoA <=> CoA + citramalate), isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), cysteine desulfhydrase (H2O + L-cysteine <=> NH3 + pyruvate + H2S), prephenate: NAD+ oxidoreductase (decarboxylating) (NAD + prephenate -> NADH + CO2 + p-hydroxyphenylpyruvate) 0.326972 0.09307 4 LMOMA output 5 CAETHG_1371, CAETHG_2721, CAETHG_2753, CAETHG_3293, CAETHG_O9O9 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine), phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ --> ADP + CO2 + phosphoenolpyruvate), isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), cysteine desulfhydrase (H2O + Lcysteine <=> NH3 + pyruvate + H2S), prephenate: NAD + oxidoreductase (decarboxylating) (NAD + prephenate -> NADH + CO2 + p-hydroxyphenylpyruvate) 0.326957 0.092998

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5 LMOMA output 4 CAETHG_0233, CAETHG_2753, CAETHG_2932, CAETHG_3293 4-imidazolone-5-propanoate amidohydrolase (H2O + 4-imidazolone-5-propanoate -> N-formimino-E-glutamate), isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), alpha-acetolactate decarboxylase ( ALCTT --> CO2 + (B)-acetoin), cysteine desulfhydrase (H2O + L-cysteine <=> NH3 + pyruvate + H2S) 0.322658 0.092572 6 LMOMA output 4 CAETHG_2753, CAETHG_2932, CAETHG_3O21, CAETHG_3293 Isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (B)-acetoin), L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), cysteine desulfhydrase (H2O + L-cysteine <=> NH3 + pyruvate + H2S) 0.322819 0.092318 7 LMOMA output 3 CAETHG_2753, CAETHG_2932, CAETHG_3293 Isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), alpha-acetolactate decarboxylase (ALCTT --> CO2 + (B)-acetoin), cysteine desulfhydrase (H2O + L-cysteine <=> NH3 + pyruvate + H2S) 0.322658 0.09231 8 LMOMA output 3 CAETHG_2753, CAETHG_3293, CAETHG_3924 Isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), cysteine desulfhydrase (H2O + Lcysteine <=> NH3 + pyruvate + H2S), O-ribose-1,5phosphomutase (ribose-1-phosphate <= > ribose 5-phosphate) 0.325822 0.091762 9 LMOMA output 3 CAETHG_0160, CAETHG_2753, CAETHG_3293 N-ribosylnicotinamide: orthophosphate ribosyltransferase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), cysteine desulfhydrase (H2O + L-cysteine <=> NH3 + pyruvate + H2S) 0.325822 0.091762 10 LMOMA output 3 CAETHG_1371, CAETHG_2753, CAETHG_3293 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine), isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), 0.325822 0.091762 cysteine desulfhydrase (H2O + L-cysteine <=> NH3 + pyruvate + H2S) eleven LMOMA output 3 CAETHG_2721, CAETHG_2753, CAETHG_3293 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ --> ADP + CO2 + phosphoenolpyruvate), isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), cysteine desulfhydrase (H2O + Lcysteine <=> NH3 + pyruvate + H2S) 0.324411 0.0913 12 LMOMA output 3 CAETHG_2721, CAETHG_3293, CAETHG_3924 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ --> ADP + CO2 + phosphoenolpyruvate), cysteine desulfhydrase (H2O + L-cysteine <=> NH3 + pyruvate + H2S), O-ribose-1,5-phosphomutase (ribose- 1phosphate <=> ribose-5-phosphate) 0.327495 0.090854 13 LMOMA output 3 CAETHG_2751, CAETHG_2753, CAETHG_3293 Citramalate synthase (H2O + pyruvate + acetyl-CoA <=> CoA + citramalate), isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), cysteine desulfhydrase (H2O + L-cysteine <=> NH3 + pyruvate + H2S) 0.322674 0.090674 14 LMOMA output 3 CAETHG_0233, CAETHG_2753, CAETHG_3293 4-imidazolone-5-propanoate amidohydrolase (H2O + 4-imidazolone-5-propanoate -> N-formimino-E-glutamate), isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), cysteine desulfhydrase (H2O + Lcysteine <=> NH3 + pyruvate + H2S) 0.322658 0.09027 15 LMOMA output 3 CAETHG_0234, CAETHG_2753, CAETHG_3293 4,5-dihydro-4-oxo-5-imidazolepropanoate hydrolyase (4imidazolone-5-propanoate <=> H2O + urocanate), isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), cysteine desulfhydrase (H2O + Lcysteine <=> NH3 + pyruvate + H2S) 0.322658 0.09027

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16 LMOMA output 3 CAETHG_2753, CAETHG_3O21, CAETHG_3293 Isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), cysteine desulfhydrase (H2O + L-cysteine <=> NH3 + pyruvate + H2S ) 0.322819 0.090256 17 LMOMA output 2 CAETHG_2753, CAETHG_3293 Isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), cysteine desulfhydrase (H2O + Lcysteine <=> NH3 + pyruvate + H2S) 0.322658 0.090044 18 LMOMA output 2 CAETHG_2932, CAETHG_3293 Alpha-acetolactate decarboxylase (ALCTT --> CO2 + (R)acetoin), cysteine desulfhydrase (H2O + L-cysteine <=> NH3 + pyruvate + H2S) 0.322658 0.089638 19 LMOMA output 2 CAETHG_0160, CAETHG_3293 N-ribosylnicotinamide: opτoφocφaτpibosyltransφerase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), cysteine desulfhydrase (H2O + Lcysteine <=> NH3 + pyruvate + H2S) 0.325822 0.0885 20 LMOMA output 2 CAETHG_0160, CAETHG_O9O9 N-ribosylnicotinamide:opτoφocφaτpibosyltransferase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), prephenate:NAD+-oxidoreductase (decarboxylating) (NAD + prephenate -> NADH + CO2 + p-hydroxyphenylpyruvate) 0.328306 0.087946 21 LMOMA output 2 CAETHG_127O, CAETHG_O9O9 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), prephenate: NAD + oxidoreductase (decarboxylating) (NAD + prephenate -> NADH + CO2 + p-hydroxyphenylpyruvate) 0.328306 0.087946 22 LMOMA output 2 CAETHG_0160, CAETHG_2721 N-ribosylnicotinamide:opτoφocφaτpibosyltransφerase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), phosphoenolpyruvate carboxykinase (RRSC) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate) 0.330562 0.08744 23 LMOMA output 1 CAETHG_O9O9 Prephenate: NAD+-oxidoreductase (decarboxylating) (NAD + prephenate -> NADH + CO2 + p- 0.32509 0.0873 hydroxyphenylpyruvate) 24 LMOMA output 1 CAETHG_0160 N-ribosylnicotinamide:opτoφocφaτpibosyltransφerase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate) 0.32887 0.087246 25 LMOMA output 1 CAETHG_1371 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine) 0.32887 0.087246 26 LMOMA output 1 CAETHG_127O AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine) 0.32887 0.087246 27 LMOMA output 1 CAETHG_3924 O-ribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose-5phosphate) 0.32887 0.087246 28 LMOMA output 1 CAETHG_2721 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate) 0.327443 0.0872 29 LMOMA output 1 CAETHG_3O21 L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline) 0.325831 0.08702

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Example 3.

This example describes disturbances to improve ethanol production in Wood-Ljungdahl microorganisms. Metabolic modeling experiments were performed as described in Example 1. Ethanol is a native product of Wood-Ljungdahl microorganisms.

ft Methodology Oh co ABOUT Disturbed genes Disturbed reactions Minimum FVA output Compliance score 1 LMOMA output 4 CAETHG_2932, CAETHG_3359, CAETHG_3510, CAETHG_0686 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (R)acetoin), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), 2,6diaminoheptanedioate: 2-oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <- 2-oxoglutarate + EE-2,6-diaminopimelate), L-threonine acetaldehyde lyase (Lthreonine --> glycine + acetaldehyde) 0.22708 0.205528 2 LMOMA output 5 CAETHG_2932, CAETHG_3O21, CAETHG_3359, CAETHG_3924, CAETHG_0498 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (R)acetoin), L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), O -ribose-1,5phosphomutase (ribose-1-phosphate <=> ribose-5-phosphate), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0.230473 0.205316 3 LMOMA output 5 CAETHG_1270, CAETHG_2932, CAETHG_3O21, CAETHG_3359, CAETHG_0498 AMP: pyrophosphate phosphoribosyltransferase (ΡΡί + AMP <=> PRPP + adenine), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (P)-acetoin), L-arginine iminohydrolase (H2O + Larginine <=> NH3 + citrulline), ATP: acetate phosphotransferase ( ATP + H+ + propionate -> ADP + propionyl phosphate), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0.230473 0.205316 4 LMOMA output 4 CAETHG_2932, CAETHG_3359, Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (R)acetoin), ATP: acetate phosphotransferase (ATP + H+ + 0.230404 0.205306

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CAETHG_3924, CAETHG_0498 propionate -> ADP + propionyl phosphate), O-ribose-1,5phosphomutase (ribose-1-phosphate <=> ribose-5-phosphate), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 5 LMOMA output 4 CAETHG_0160, CAETHG_2932, CAETHG_3359, CAETHG_0498 N-ribosylnicotinamide: opτoφocφaτpibosyltransφerase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), ATP: acetate phosphotransferase (ATP + H+ + propionate - > ADP + propionyl phosphate), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0.230404 0.205306 6 LMOMA output 4 CAETHG_127O, CAETHG_2932, CAETHG_3359, CAETHG_0498 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), cystathionine -betaliase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0.230404 0.205306 7 LMOMA output 3 CAETHG_1371, CAETHG_2932, CAETHG_3358 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0.230833 0.205248 8 LMOMA output 3 CAETHG_2932, CAETHG_3359, CAETHG_3924 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (R)acetoin), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), O-ribose-1,5phosphomutase (ribose-1-phosphate <=> ribose- 5-phosphate) 0.230833 0.205248 9 LMOMA output 3 CAETHG_0160, CAETHG_2932, CAETHG_3358 N-ribosylnicotinamide:opτoφocφaτpibosyltransφerase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), phosphate transacetylase (phosphate + ace til-CoA + H+ < => CoA + acetyl phosphate) 0.230833 0.205248 10 LMOMA output 3 CAETHG_127O, CAETHG_2932, CAETHG_3358 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), phosphate transacetylase (phosphate + acetylCoA + H+ <=> CoA + acetylphosphate) 0.230833 0.205248 eleven LMOMA output 3 CAETHG_2932, CAETHG_3358, CAETHG_3924 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (R)acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), O-ribose-1,5-phosphomutase (ribose1-phosphate <=> ribose -5-phosphate) 0.230833 0.205248 12 LMOMA output 3 CAETHG_2932, CAETHG_3358, CAETHG_0498 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (R)acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate), cystathionine beta-lyase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0.228988 0.205226 13 LMOMA output 3 CAETHG_2932, CAETHG_3021, CAETHG_3358 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (R)acetoin), L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), phosphate transacetylase (phosphate + acetylCoA + H+ <=> CoA + acetylphosphate) 0.229481 0.205172 14 LMOMA output 2 CAETHG_2932, CAETHG_3359 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (R)acetoin), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0.229408 0.205162 15 LMOMA output 2 CAETHG_2932, CAETHG_3358 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (R)acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0.229408 0.205162 16 LMOMA output 3 CAETHG_2721, CAETHG_2932, CAETHG_3924 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ --> ADP + CO2 + phosphoenolpyruvate), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (R)acetoin), O-ribose-1,5-phosphomutase (ribose-1- phosphate <=> ribose-5-phosphate) 0.188313 0.194484

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17 LMOMA output 3 CAETHG_3O21, CAETHG_3358, CAETHG_3510 L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), 2,6-diaminoheptanedioate:2oxoglutarate aminotransferase (H2O + L-glutamate + H + + tetrahydrodipicolinate <- 2-oxoglutarate + LL-2,6- diaminopimelate) 0.221462 0.188812 18 LMOMA output 2 CAETHG_3358, CAETHG_3510 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), 2,6-diaminoheptanedioate:2- oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <- 2-oxoglutarate + LL-2,6- diaminopimelate) 0.221395 0.188806 19 LMOMA output 3 CAETHG_3358, CAETHG_3924, CAETHG_0498 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate), O-ribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose-5-phosphate), cystathionine beta-lyase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0.230404 0.188442 20 LMOMA output 3 CAETHG_0160, CAETHG_3358, CAETHG_0498 N-ribosylnicotinamide: orthophosphate ribosyltransferase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), phosphate transacetylase (phosphate + acetylCoA + H+ <=> CoA + acetylphosphate), cystathionine beta-lyase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0.230404 0.188442 21 LMOMA output 3 CAETHG_1371, CAETHG_3358, CAETHG_0498 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), cystathionine betaliase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0.230404 0.188442 22 LMOMA output 2 CAETHG_3358, CAETHG_0498 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), cystathionine beta-lyase (H2O + cystathionine - -> NH3 + pyruvate + homocysteine) 0.228988 0.188404 23 LMOMA output 2 CAETHG_3359, CAETHG_0498 ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), cystathionine beta-lyase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0.228988 0.188404 24 LMOMA output 3 CAETHG_3O21, CAETHG_3358, CAETHG_3924 L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), O-ribose-1,5-phosphomutase (ribose1-phosphate <= > ribose 5-phosphate) 0.230902 0.188398 25 LMOMA output 2 CAETHG_1270, CAETHG_3359 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0.230833 0.18839 26 LMOMA output 2 CAETHG_1371, CAETHG_3359 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0.230833 0.18839 27 LMOMA output 2 CAETHG_3359, CAETHG_3924 ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), O-ribose-1,5-phosphomutase (ribose-1phosphate <=> ribose-5-phosphate) 0.230833 0.18839 28 LMOMA output 2 CAETHG_1371, CAETHG_3358 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate) 0.230833 0.18839 29 LMOMA output 1 CAETHG_3358 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0.229408 0.188348 thirty LMOMA output 1 CAETHG_3359 ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0.229408 0.188348 31 LMOMA output 2 CAETHG_0160, CAETHG_2932 N-ribosylnicotinamide: orthophosphate ribosyltransferase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin) 0.185926 0.186556 32 Exit - 2 CAETHG_2932, Alpha acetolactate decarboxylase (ALCTT -> CO2 + (R)- 0.185926 0.186556

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LMOMA CAETHG_3924 acetoin), O-ribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose-5-phosphate) 33 LMOMA output 2 CAETHG_2932, CAETHG_3293 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (R)acetoin), cysteine desulfhydrase (H2O + L-cysteine <=> NH3 + pyruvate + H2S) 0.183754 0.184984 34 LMOMA output 2 CAETHG_2932, CAETHG_0498 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (R)acetoin), cystathionine beta-lyase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0.183906 0.184562 35 LMOMA output 2 CAETHG_2796, CAETHG_2932 NADP-dependent electron bifurcation [FeFe]- dehydrogenase (Hyt) (NADP + oxidized ferredoxin + 2.0 H2 <=> NADPH + 3.0 H+ + reduced ferredoxin), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (R)acetoin) 0.183806 0.18449 36 LMOMA output 2 CAETHG_2798, CAETHG_2932 NADP-dependent electron bifurcation [FeFe]- dehydrogenase (Hyt) (NADP + oxidized ferredoxin + 2.0 H2 <=> NADPH + 3.0 H+ + reduced ferredoxin), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (R)acetoin) 0.183806 0.18449 37 LMOMA output 2 CAETHG_2799, CAETHG_2932 NADP-dependent electron bifurcation [FeFe]- dehydrogenase (Hyt) (NADP + oxidized ferredoxin + 2.0 H2 <=> NADPH + 3.0 H+ + reduced ferredoxin), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (R)acetoin) 0.183806 0.18449 38 LMOMA output 2 CAETHG_2795, CAETHG_2932 NADP-dependent electron bifurcation [FeFe]- dehydrogenase (Hyt) (NADP + oxidized ferredoxin + 2.0 H2 <=> NADPH + 3.0 H+ + reduced ferredoxin), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (R)acetoin) 0.183806 0.18449 39 LMOMA output 2 CAETHG_2797, CAETHG_2932 NADP-dependent electron bifurcation [FeFe]- dehydrogenase (Hyt) (NADP + oxidized ferredoxin + 2.0 H2 <=> NADPH + 3.0 H+ + reduced ferredoxin), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (R)acetoin) 0.183806 0.18449 40 LMOMA output 2 CAETHG_0248, CAETHG_2932 Reversible transport of L-lactate in symport with protons (H+_nar. + E-lactate_nar. <=> H+ + L-lactate), alpha-acetolactate decarboxylase (ALCTT --> CO2 + (P)-acetoin) 0.183806 0.184038 41 LMOMA output 2 CAETHG_2751, CAETHG_2932 Citramalate synthase (H2O + pyruvate + acetyl-CoA <=> CoA + citramalate), alpha-acetolactate decarboxylase (ALCTT --> CO2 + (P)-acetoin) 0.183456 0.184024 42 LMOMA output 2 CAETHG_3924, CAETHG_0498 O-ribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose-5phosphate), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0.186014 0.183362 43 LMOMA output 1 CAETHG_0160 N-ribosylnicotinamide:orthophosphate ribosyltransferase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate) 0.185926 0.182994 44 LMOMA output 1 CAETHG_127O AMP: pyrophosphate phosphoribosyltransferase (PΡί + AMP <=> PRPP + adenine) 0.185926 0.182994 45 LMOMA output 1 CAETHG_3924 O-ribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose-5phosphate) 0.185926 0.182994 46 LMOMA output 1 CAETHG_2721 Phosphoenolpyruvate carboxykinase (PPKK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate) 0.185926 0.182756 47 LMOMA output 1 CAETHG_3O21 L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline) 0.186476 0.182602

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Example 4.

This example describes disturbances to improve acetone production in Wood-Ljungdahl microorganisms. Metabolic modeling experiments were performed as described in example 1. Acetone production in Wood-Ljungdahl microorganisms is described, for example, in WO 2012/115527. To model the production of acetone, the following path was used: 2.0 acetyl-CoA—CoA + acetoacetylCoA; acetate+acetoacetyl-CoA—acetyl-CoA+acetoacetate; acetoacetate-A'Cb+ceton; acetone—acetonnar.

ft Methodology Qty Disturbed genes Disturbed reactions Minimum FVA output Compliance score 1 LMOMA output 5 CAETHG_2721, CAETHG_2753, CAETHG_3358, CAETHG_3510, CAETHG_O9O9 Acetyl-CoA: carbon dioxide ligase (ADP-forming) (ATP + acetyl-CoA + H2CO3 -> ADP + phosphate + H+ + malonyl-CoA), phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), 2,6-diaminoheptanedioate:2- oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6- diaminopimelate), prephenate: NAD+-oxidoreductase (decarboxylating) (NAD + prephenate --> NADH + CO2 + phydroxyphenylpyruvate) 0 0.057267 2 LMOMA output 4 CAETHG_2721, CAETHG_3358, CAETHG_3510, CAETHG_O9O9 Acetyl-CoAzharbondioxide ligase (ADP-forming) (ATP + acetyl-CoA + H2CO3 -> ADP + phosphate + H+ + malonyl-CoA), phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate ), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), 2,6diaminoheptanedioate:2-oxoglutarate aminotransferase (H2O + Lglutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6diaminopimelate), prephenate:NAD+-oxidoreductase (decarboxylating) (NAD + prephenate --> NADH + CO2 + phydroxyphenylpyruvate) 0 0.05724 3 LMOMA output 2 CAETHG_2721, CAETHG_3359 Acetyl-CoAzharbondioxide ligase (ADP-forming) (ATP + acetyl-CoA + H2CO3 -> ADP + phosphate + H+ + malonyl-CoA), phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate ), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.056697 4 LMOMA output 3 CAETHG_2721, CAETHG_3359, CAETHG_O9O9 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), prephenate: NAD+ oxidoreductase (decarboxylating) (NAD + prephenate --> NADH + CO2 + phydroxyphenylpyruvate) 0 0.056481 5 LMOMA output 3 CAETHG_2721, CAETHG_3359, CAETHG_3510 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), 2,6-diaminoheptanedioate: 2- 0 0.056292

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oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6- diaminopimelate) 6 LMOMA output 3 CAETHG_2721, CAETHG_2753, CAETHG_3359 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.056154 7 LMOMA output 2 CAETHG_2721, CAETHG_3358 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate) 0 0.056112 8 LMOMA output 2 CAETHG_2721, CAETHG_3359 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.056112 9 LMOMA output 2 CAETHG_2721, CAETHG_3359 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.056022 10 LMOMA output 2 CAETHG_2932, CAETHG_3358 Alpha-acetolactate decarboxylase (ALCTT --> CO2 + (K)-acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.055245 eleven LMOMA output 2 CAETHG_2932, CAETHG_3359 Alpha-acetolactate decarboxylase (ALCTT --> CO2 + (K)-acetoin), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.055245 12 LMOMA output 3 CAETHG_0233, CAETHG_3359, CAETHG_3510 4-imidazolone-5-propanoate amidohydrolase (H2O + 4-imidazolone 5-propanoate -> N-formimino-E-glutamate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), 2,6-diaminoheptanedioate: 2- oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6- diaminopimelate) 0 0.05214 13 LMOMA output 3 CAETHG_0234, CAETHG_3359, CAETHG_3510 4,5-dihydro-4-oxo-5-imidazolepropanoate hydrolyase (4- imidazolone-5-propanoate <=> H2O + urocanate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), 2,6-diaminoheptanedioate: 2- oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6- diaminopimelate) 0 0.05214 14 LMOMA output 2 CAETHG_3359, CAETHG_3510 ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), 2,6-diaminoheptanedioate: 2- oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6- diaminopimelate) 0 0.052041 15 LMOMA output 2 CAETHG_3358, CAETHG_3510 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), 2,6-diaminoheptanedioate:2- oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6- diaminopimelate) 0 0.052041 16 LMOMA output 3 CAETHG_0160, CAETHG_3359, CAETHG_0909 N-ribosylnicotinamide: opτoφocφaτpibosyltransφerase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), prephenate: NAD+-oxide reductase (decarboxylating) (NAD + prephenate --> NADH + CO2 + phydroxyphenylpyruvate) 0 0.051891 17 LMOMA output 3 CAETHG_0160, CAETHG_3359, N-ribosylnicotinamide:opτoφocφaτpibosyltransφerase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), 0 0.051678

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CAETHG_0498 ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), cystathionine beta-lyase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 18 LMOMA output 3 CAETHG_1371, CAETHG_2753, CAETHG_3359 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine), isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0 0.051609 19 LMOMA output 3 CAETHG_0160, CAETHG_3021, CAETHG_3359 N-ribosylnicotinamide: opτoφocφaτpibosyltransferase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), Larginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.05157 20 LMOMA output 2 CAETHG_0160, CAETHG_3359 N-ribosylnicotinamide: opτoφocφaτpibosyltransferase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.051567 21 LMOMA output 2 CAETHG_3358, CAETHG_3924 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate), O-ribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose-5-phosphate) 0 0.051567 22 LMOMA output 2 CAETHG_1371, CAETHG_3359 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.051567 23 LMOMA output 2 CAETHG_3359, CAETHG_3924 ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), O-ribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose-5-phosphate) 0 0.051567 24 LMOMA output 2 CAETHG_1270, CAETHG_3359 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0 0.051561 25 LMOMA output 2 CAETHG_3359, CAETHG_0686 ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), L-threonine acetaldehyde lyase (L-threonine --> glycine + acetaldehyde) 0 0.048294 26 LMOMA output 2 CAETHG_3359, CAETHG_0498 ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), cystathionine beta-lyase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0 0.046551 27 LMOMA output 2 CAETHG_3293, CAETHG_3359 Cysteine desulfhydrase (H2O + L-cysteine <=> NH3 + pyruvate + H2S), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.045591 28 LMOMA output 2 CAETHG_3299, CAETHG_3359 2-deoxy-O-ribose-5-phosphate acetaldehyde lyase (deoxyribose 5-phosphate <=> acetaldehyde + glyceraldehyde-3-phosphate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.045288 29 LMOMA output 2 CAETHG_2475, CAETHG_3359 dGTP triphosphohydrolase (H2O + dGTP --> H+ + deoxyguanosine + triphosphate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.045285 thirty LMOMA output 2 CAETHG_3021, CAETHG_3359 L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.044994 31 LMOMA output 2 CAETHG_3164, CAETHG_3359 UMP: pyrophosphate phosphoribosyltransferase (uracil + PRPP --> PPi + UMP), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0 0.044943 32 LMOMA output 1 CAETHG_3359 ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0 0.04494 33 LMOMA output 1 CAETHG_3358 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.04494 34 LMOMA output 2 CAETHG_0234, CAETHG_2751 4,5-dihydro-4-oxo-5-imidazolepropanoate hydrolyase (4- imidazolone-5-propanoate <=> H2O + urocanate), citramalate synthase (H2O + pyruvate + acetyl-CoA <=> CoA + citramalate) 0 0.020286 35 LMOMA output 1 CAETHG_2751 Citramalate synthase (H2O + pyruvate + acetyl-CoA <=> CoA + citramalate) 0 0.020283 36 LMOMA output 1 CAETHG_1371 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine) 0 0.020094 37 LMOMA output 1 CAETHG_1270 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine) 0 0.020094 38 LMOMA output 1 CAETHG_3924 O-ribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose-5- phosphate) 0 0.020094

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Example 5.

This example describes disturbances to improve isopropanol production in Wood-Ljungdahl microorganisms. Metabolic modeling experiments were performed as described in example 1. Isopropanol production in Wood-Ljungdahl microorganisms is described, for example, in WO 2012/115527. The following pathway was used to model isopropanol production in this paper: 2.0 acetyl-CoA—CoA+acetoacetyl-CoA; acetate+acetoacetyl-CoA—acetyl-CoA+acetoacetate;

acetoacetate- -CO2αcetone; isopropanol—isopropanolnar.

ft Methodology Oh co ABOUT Disturbed genes Disturbed reactions Minimum FVA output Compliance score 1 LMOMA output 6 CAETHG_2753, CAETHG_2932, CAETHG_3021, CAETHG_3358, CAETHG_O498, CAETHG_O686 Isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2oxoglutarate + H+), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (Rj-acetoin), L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), phosphate transacetylase (phosphate + acetylCoA + H+ <=> CoA + acetylphosphate), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine), L-threonine acetaldehyde lyase (L-threonine -> glycine + acetaldehyde) 0 0.04386 2 LMOMA output 5 CAETHG_2753, CAETHG_2932, CAETHG_3358, CAETHG_O498, CAETHG_O686 Isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2oxoglutarate + H+), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (B)-acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate ), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine), L-threonine acetaldehyde lyase (L-threonine --> glycine + acetaldehyde) 0 0.043854 3 LMOMA output 6 CAETHG_2932, CAETHG_3021, CAETHG_3358, CAETHG_3510, CAETHG_O498, CAETHG_O686 Alpha-acetolactate decarboxylase (ALCTT --> CO2 + (K)-acetoin), L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate), 2,6-diaminoheptanedioate:2- oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <- 2-oxoglutarate + LL-2,6- diaminopimelate), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine), L-threonine acetaldehyde lyase (Lthreonine -> glycine + acetaldehyde) 0 0.043791

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4 LMOMA output 5 CAETHG_2932, CAETHG_3358, CAETHG_351O, CAETHG_0498, CAETHG_0686 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), 2,6-diaminoheptanedioate:2- oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <- 2-oxoglutarate + LL-2,6- diaminopimelate), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine), L-threonine acetaldehyde lyase (Lthreonine -> glycine + acetaldehyde) 0 0.043782 5 LMOMA output 5 CAETHG_2932, CAETHG_3O21, CAETHG_3358, CAETHG_0498, CAETHG_0686 Alpha-acetolactate decarboxylase (ALCTT --> CO2 + (K)-acetoin), L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine), L-threonine acetaldehyde lyase (Lthreonine -> glycine + acetaldehyde) 0 0.04377 6 LMOMA output 4 CAETHG_2932, CAETHG_3359, CAETHG_0498, CAETHG_0686 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), cystathionine beta-lyase (H2O + cystathionine > NH3 + pyruvate + homocysteine) , L-threonine acetaldehyde lyase (Lthreonine -> glycine + acetaldehyde) 0 0.043758 7 LMOMA output 4 CAETHG_2932, CAETHG_3358, CAETHG_0498, CAETHG_0686 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (Rj-acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine ), L-threonine acetaldehyde lyase (Lthreonine -> glycine + acetaldehyde) 0 0.043758 8 LMOMA output 3 CAETHG_2932, CAETHG_3358, CAETHG_0686 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), L-threonine acetaldehyde lyase (L-threonine --> glycine + acetaldehyde) 0 0.043644 9 LMOMA output 3 CAETHG_2932, CAETHG_3359, CAETHG_0686 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), L-threonine acetaldehyde lyase (L-threonine -> glycine + acetaldehyde) 0 0.043644 10 LMOMA output 4 CAETHG_2932, CAETHG_3021, CAETHG_3359, CAETHG_0498 Alpha-acetolactate decarboxylase (ALCTT --> CO2 + (K)-acetoin), L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), cystathionine beta-lyase (H2O + cystathionine > NH3 + pyruvate + homocysteine) 0 0.043107 eleven LMOMA output 3 CAETHG_2932, CAETHG_3358, CAETHG_0498 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0 0.043095 12 LMOMA output 3 CAETHG_2932, CAETHG_3359, CAETHG_0498 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), cystathionine beta-lyase (H2O + cystathionine > NH3 + pyruvate + homocysteine) 0 0.043095 13 LMOMA output 3 CAETHG_1371, CAETHG_2932, CAETHG_3359 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0 0.04308 14 LMOMA output 3 CAETHG_0160, CAETHG_2932, CAETHG_3359 M-ribosylnicotinamide: orthophosphate ribosyltransferase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), ATP: acetate phosphotransferase (ATP + H+ + propionate - -> ADP + propionyl phosphate) 0 0.04308 15 LMOMA output 3 CAETHG_2932, CAETHG_3021, CAETHG_3359 Alpha-acetolactate decarboxylase (ALCTT --> CO2 + (K)-acetoin), L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0 0.043029

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16 LMOMA output 3 o, CAETHG_2932, CAETHG_3359 Acetyl-CoAzharbondioxide ligase (ADP-forming) (ATP + acetyl-CoA + H2CO3 -> ADP + phosphate + H+ + malonyl-CoA), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), ATP: acetate phosphotransferase ( ATP + H+ + propionate --> ADP + propionyl phosphate) 0 0.043023 17 LMOMA output 2 CAETHG_2932, CAETHG_3359 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0 0.043017 18 LMOMA output 2 CAETHG_2932, CAETHG_3358 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.043017 19 LMOMA output 3 CAETHG_3359, CAETHG_0498, CAETHG_0686 ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), cystathionine beta-lyase (H2O + cystathionine > NH3 + pyruvate + homocysteine), L-threonine acetaldehyde lyase (Lthreonine -> glycine + acetaldehyde) 0 0.037755 20 LMOMA output 3 CAETHG_3021, CAETHG_3359, CAETHG_0686 L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), L-threonine acetaldehyde lyase (L-threonine -> glycine + acetaldehyde) 0 0.037077 21 LMOMA output 2 CAETHG_3358, CAETHG_0686 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), L-threonine acetaldehyde lyase (L-threonine --> glycine + acetaldehyde) 0 0.037038 22 LMOMA output 2 CAETHG_3359, CAETHG_0686 ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), L-threonine acetaldehyde lyase (L-threonine -> glycine + acetaldehyde) 0 0.037038 23 LMOMA output 3 CAETHG_2441, CAETHG_3293, CAETHG_3359 Pyruvate kinase (ADP + phosphoenolpyruvate -> ATP + pyruvate), cysteine desulfhydrase (H2O + L-cysteine <=> NH3 + pyruvate + H2S), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0 0.036639 24 LMOMA output 3 CAETHG_3293, CAETHG_3359, CAETHG_0498 Cysteine desulfhydrase (H2O + L-cysteine <=> NH3 + pyruvate + H2S), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0 0.036468 25 LMOMA output 2 CAETHG_3293, CAETHG_3359 Cysteine desulfhydrase (H2O + L-cysteine <=> NH3 + pyruvate + H2S), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0 0.035355 26 LMOMA output 2 CAETHG_0234, CAETHG_3359 4,5-dihydro-4-oxo-5-imidazolepropanoate hydrolyase (4- imidazolone-5-propanoate <=> H2O + urocanate), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0 0.031752 27 LMOMA output 2 CAETHG_0233, CAETHG_3359 4-imidazolone-5-propanoate amidohydrolase (H2O + 4-imidazolone 5-propanoate --> N-formimino-E-glutamate), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0 0.031752 28 LMOMA output 2 CAETHG_3021, CAETHG_3359 L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0 0.031737 29 LMOMA output 2 CAETHG_2475, CAETHG_3359 dGTP triphosphohydrolase (H2O + dGTP -> H+ + deoxyguanosine + triphosphate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.031731 thirty LMOMA output 2 CAETHG_2475, CAETHG_3358 dGTP triphosphohydrolase (H2O + dGTP -> H+ + deoxyguanosine + triphosphate), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate) 0 0.031731 31 LMOMA output 1 CAETHG_3358 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.031707 32 LMOMA output 1 CAETHG_3359 ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.031707

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Example 6.

This example describes disturbances to improve lactate production in WoodLjungdahl microorganisms. Metabolic modeling experiments were performed as described in Example 1. Lactate is a native product of Wood-Ljungdahl microorganisms.______________________

ft Methodology About co ABOUT Disturbed genes Disturbed reactions Minimum FVA output Compliance score 1 BPCY- FBA 4 CAETHG_2753, CAETHG_29O9, CAETHG_3293, CAETHG_3358 Isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2oxoglutarate + H+), ATP:pyruvate-orthophosphate phosphotransferase (ATP + phosphate + pyruvate + H+ -> PPi + AMP + phosphoenolpyruvate), cysteine desulfhydrase (H2O + L-cysteine <= > NH3 + pyruvate + H2S), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.011882 2 BPCY- FBA 4 CAETHG_2753, CAETHG_29O9, CAETHG_3293, CAETHG_3359 Isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2oxoglutarate + H+), ATP:pyruvate-orthophosphate phosphotransferase (ATP + phosphate + pyruvate + H+ -> PPi + AMP + phosphoenolpyruvate), cysteine desulfhydrase (H2O + L-cysteine <= > NH3 + pyruvate + H2S), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.011882 3 BPCY- FBA 4 CAETHG_2751, CAETHG_2753, CAETHG_29O9, CAETHG_3358 Citramalate synthase (H2O + pyruvate + acetyl-CoA <=> CoA + citramalate), isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), ATP:pyruvate- orthophosphate phosphotransferase (ATP + phosphate + pyruvate + H+ -> PPi + AMP + phosphoenolpyruvate), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate) 0 0.011873 4 BPCY- FBA 4 CAETHG_2753, CAETHG_29O9, CAETHG_3358, CAETHG_0498 Isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2oxoglutarate + H+), ATP:pyruvate-orthophosphate phosphotransferase (ATP + phosphate + pyruvate + H+ -> PPi + AMP + phosphoenolpyruvate), phosphate transacetylase (phosphate + acetyl-CoA + H + <=> CoA + acetyl phosphate), cystathionine beta-lyase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0 0.011786 5 BPCY- FBA 3 CAETHG_2753, CAETHG_29O9, CAETHG_3358 Isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2oxoglutarate + H+), ATP:pyruvate-orthophosphate phosphotransferase (ATP + phosphate + pyruvate + H+ -> PPi + AMP + phosphoenolpyruvate), phosphate transacetylase (phosphate + acetyl-CoA + H + <=> CoA + acetyl phosphate) 0 0.011696 6 BPCY- FBA 3 CAETHG_2751, CAETHG_29O9, CAETHG_3358 Citramalate synthase (H2O + pyruvate + acetyl-CoA <=> CoA + citramalate), ATP:pyruvate-orthophosphate phosphotransferase (ATP + phosphate + pyruvate + H+ -> PPi + AMP + phosphoenolpyruvate), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.010722 7 BPCY- FBA 2 CAETHG_29O9, CAETHG_3359 ATP: pyruvate orthophosphate phosphotransferase (ATP + phosphate + pyruvate + H+ -> PPi + AMP + phosphoenolpyruvate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.010534

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8 BPCY- FBA 2 CAETHG_2909, CAETHG_3358 ATP: pyruvate orthophosphate phosphotransferase (ATP + phosphate + pyruvate + H+ -> PPi + AMP + phosphoenolpyruvate), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.010534 9 BPCY- FBA 2 CAETHG_2909, CAETHG_3358 ATP: pyruvate orthophosphate phosphotransferase (ATP + phosphate + pyruvate + H+ -> PPi + AMP + phosphoenolpyruvate), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.010387 10 BPCY- FBA 3 CAETHG_2753, CAETHG_3293, CAETHG_3358 Isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2oxoglutarate + H+), cysteine desulfhydrase (H2O + L-cysteine <=> NH3 + pyruvate + H2S), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.010038 eleven BPCY- FBA 3 CAETHG_2751, CAETHG_2753, CAETHG_3358 Citramalate synthase (H2O + pyruvate + acetyl-CoA <=> CoA + citramalate), isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.00988 12 BPCY- FBA 2 CAETHG_2753, CAETHG_3358 Isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2oxoglutarate + H+), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.009678 13 BPCY- FBA 2 CAETHG_2753, CAETHG_3358 Isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2oxoglutarate + H+), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.009586 14 BPCY- FBA 2 CAETHG_2751, CAETHG_3359 Citramalate synthase (H2O + pyruvate + acetyl-CoA <=> CoA + citramalate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.008686 15 BPCY- FBA 2 CAETHG_2751, CAETHG_3358 Citramalate synthase (H2O + pyruvate + acetyl-CoA <=> CoA + citramalate), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.008686 16 BPCY- FBA 1 CAETHG_3359 ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0 0.008474 17 BPCY- FBA 1 CAETHG_3358 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.008474 18 BPCY- FBA 2 CAETHG_2753, CAETHG_2909 Isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2oxoglutarate + H+), ATP:pyruvate-orthophosphate phosphotransferase (ATP + phosphate + pyruvate + H+ --> PPi + AMP + phosphoenolpyruvate) 0 0.001316 19 LMOMA output 5 CAETHG_2210, CAETHG_2224, CAETHG_2798, CAETHG_2932, CAETHG_3299 NADP-dependent electron bifurcation [FeFeJ-dehydrogenase (Hyt) (NADP + oxidized ferredoxin + 2.0 H2 <=> NADPH + 3.0 H+ + reduced ferredoxin), alpha acetolactate decarboxylase (ALCTT --> CO2 + (K)-acetoin), 2deoxy-0-ribose-5-phosphate acetaldehyde lyase (deoxyribose-5phosphate <=> acetaldehyde + glyceraldehyde-3-phosphate) 0 0.036108 20 LMOMA output 5 CAETHG_2210, CAETHG_2224, CAETHG_2798, CAETHG_2932, CAETHG_3021 NADP-dependent electron bifurcation [FeFeJ-dehydrogenase (Hyt) (NADP + oxidized ferredoxin + 2.0 H2 <=> NADPH + 3.0 H+ + reduced ferredoxin), alpha acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline) 0 0.035997 21 LMOMA output 5 CAETHG_2210, CAETHG_2224, CAETHG_2475, CAETHG_2798, CAETHG_2932 dGTP triphosphohydrolase (H2O + dGTP -> H+ + deoxyguanosine + triphosphate), NADP-dependent electron bifurcation [FeFeJdehydrogenase (Hyt) (NADP + oxidized ferredoxin + 2.0 H2 <=> NADPH + 3.0 H+ + reduced ferredoxin), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin) 0 0.035826 22 LMOMA output 5 CAETHG_2210, CAETHG_2224, CAETHG_2798, CAETHG_2932, CAETHG_3164 NADP-dependent electron bifurcation [FeFeJ-dehydrogenase (Hyt) (NADP + oxidized ferredoxin + 2.0 H2 <=> NADPH + 3.0 H+ + reduced ferredoxin), alpha acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), UMP: pyrophosphate phosphoribosyltransferase (uracil + PRPP -> PPi 0 0.035799

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+ UMF) 23 LMOMA output 4 CAETHG_2210, CAETHG_2224, CAETHG_2799, CAETHG_2932 NADP-dependent electron bifurcation [FeFeJ-dehydrogenase (Hyt) (NADP + oxidized ferredoxin + 2.0 H2 <=> NADPH + 3.0 H+ + reduced ferredoxin), alpha acetolactate decarboxylase (ALCTT -> CO2 + (B)-acetoin) 0 0.035754 24 LMOMA output 4 CAETHG_2210, CAETHG_2224, CAETHG_2795, CAETHG_2932 NADP-dependent electron bifurcation [FeFeJ-dehydrogenase (Hyt) (NADP + oxidized ferredoxin + 2.0 H2 <=> NADPH + 3.0 H+ + reduced ferredoxin), alpha acetolactate decarboxylase (ALCTT -> CO2 + (B)-acetoin) 0 0.035754 25 LMOMA output 4 CAETHG_2210, CAETHG_2224, CAETHG_2794, CAETHG_2932 NADP-dependent electron bifurcation [FeFeJ-dehydrogenase (Hyt) (NADP + oxidized ferredoxin + 2.0 H2 <=> NADPH + 3.0 H+ + reduced ferredoxin), alpha acetolactate decarboxylase (ALCTT -> CO2 + (B)-acetoin) 0 0.035754 26 LMOMA output 4 CAETHG_2210, CAETHG_2224, CAETHG_2798, CAETHG_2932 NADP-dependent electron bifurcation [FeFeJ-dehydrogenase (Hyt) (NADP + oxidized ferredoxin + 2.0 H2 <=> NADPH + 3.0 H+ + reduced ferredoxin), alpha acetolactate decarboxylase (ALCTT -> CO2 + (B)-acetoin) 0 0.035754 27 LMOMA output 4 CAETHG_2210, CAETHG_2224, CAETHG_2798, CAETHG_2932 NADP-dependent electron bifurcation [FeFeJ-dehydrogenase (Hyt) (NADP + oxidized ferredoxin + 2.0 H2 <=> NADPH + 3.0 H+ + reduced ferredoxin), alpha acetolactate decarboxylase (ALCTT -> CO2 + (B)-acetoin) 0 0.035748 28 LMOMA output 5 CAETHG_2210, CAETHG_2211, CAETHG_2224, CAETHG_2932, CAETHG_3299 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (B)-acetoin), 2-deoxy-O-ribose-5-phosphate acetaldehyde lyase (deoxyribose 5-phosphate <=> acetaldehyde + glyceraldehyde-3-phosphate) 0 0.034086 29 LMOMA output 5 CAETHG_1757, CAETHG_2210, CAETHG_2224, CAETHG_2932, CAETHG_3299 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (B)-acetoin), 2-deoxy-O-ribose-5-phosphate acetaldehyde lyase (deoxyribose 5-phosphate <=> acetaldehyde + glyceraldehyde-3-phosphate) 0 0.034086 thirty LMOMA output 5 CAETHG_2210, CAETHG_2224, CAETHG_2339, CAETHG_2932, CAETHG_3299 dCMP aminohydrolase (H2O + H+ + dCMP --> NH3 + dUMP), alpha-acetolactate decarboxylase (ALCTT --> CO2 + (R)-acetoin), 2deoxy-O-ribose-5-phosphate acetaldehyde lyase (deoxyribose-5phosphate <= > acetaldehyde + glyceraldehyde-3-phosphate) 0 0.034086 31 LMOMA output 5 CAETHG_2210, CAETHG_2224, CAETHG_2932, CAETHG_3299, CAETHG_3985 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (P)-acetoin), 2-deoxy-O-ribose-5-phosphate acetaldehyde lyase (deoxyribose 5-phosphate <=> acetaldehyde + glyceraldehyde-3-phosphate), arsenate transporter (arsenate -> arsenate_nar .) 0 0.034086 32 LMOMA output 5 CAETHG_2210, CAETHG_2224, CAETHG_2633, CAETHG_2932, CAETHG_3299 N-acetylneuraminate pyruvate lyase (pyruvate phosphorylating) (H2O + phosphoenolpyruvate + N-acetyl-O-mannosamine -> phosphate + H+ + Neu5Ac), alpha-acetolactate decarboxylase (ALCTT --> CO2 + (P)-acetoin), 2-deoxy-O -ribose-5-phosphate acetaldehyde lyase (deoxyribose-5-phosphate <=> acetaldehyde + glyceraldehyde-3phosphate) 0 0.034086 33 LMOMA output 6 CAETHG_2210, CAETHG_2224, CAETHG_2548, CAETHG_2932, CAETHG_3299, CAETHG_0832 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (P)-acetoin), 2-deoxy-O-ribose-5-phosphate acetaldehyde lyase (deoxyribose 5-phosphate <=> acetaldehyde + glyceraldehyde-3-phosphate), thiazole phosphate synthesis (ATP + L- Tyrosine + L-cysteine + 1-deoxy-oxylulose-5-phosphate -> H2O + CO2 + ΡΡί + AMP + L-alanine + 4methyl-5-2-phosphoethylthiazole + 4-hydroxybenzyl alcohol) 0 0.034086 34 LMOMA output 7 CAETHG_2210, CAETHG_2224, CAETHG_2932, CAETHG_3299, Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (P)-acetoin), 2-deoxy-O-ribose-5-phosphate acetaldehyde lyase (deoxyribose- 5-phosphate <=> acetaldehyde + glyceraldehyde-3-phosphate) 0 0.034086

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CAETHG_3850, CAETHG_0417, CAETHG_0461 35 LMOMA output 4 CAETHG_2210, CAETHG_2224, CAETHG_2932, CAETHG_3299 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (P)-acetoin), 2-deoxy-O-ribose-5-phosphate acetaldehyde lyase (deoxyribose 5-phosphate <=> acetaldehyde + glyceraldehyde-3-phosphate) 0 0.034086 36 LMOMA output 5 CAETHG_2210, CAETHG_2224, CAETHG_2618, CAETHG_2932, CAETHG_3299 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (B)-acetoin), 2-deoxy-O-ribose-5-phosphate acetaldehyde lyase (deoxyribose 5-phosphate <=> acetaldehyde + glyceraldehyde-3-phosphate) 0 0.034086 37 LMOMA output 3 CAETHG_2107, CAETHG_2932, CAETHG_3021 Potassium absorption (K+_nar. <=> K+), alpha acetolactate decarboxylase (ALCTT -> CO2 + (B)-acetoin), L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline) 0 0.026043 38 LMOMA output 2 CAETHG_2932, CAETHG_3021 Alpha-acetolactate decarboxylase (ALCTT --> CO2 + (B)-acetoin), L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline) 0 0.025995 39 LMOMA output 2 CAETHG_2107, CAETHG_2932 Potassium absorption (K+_nar. <=> K+), alpha acetolactate decarboxylase (ALCTT -> CO2 + (Rj-acetoin) 0 0.024423 40 LMOMA output 1 CAETHG_2932 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (P)-acetoin) 0 0.024375 41 LMOMA output 2 CAETHG_1225, CAETHG_0160 L-serine ammonia lyase (L-serine -> NH3 + pyruvate), Nribosylnicotinamide:orthophosphate ribosyltransferase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate) 0 0.021384 42 LMOMA output 1 CAETHG_0160 N-ribosylnicotinamide:opτoφocφaτpibosyltransφerase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate) 0 0.021204 43 LMOMA output 1 CAETHG_1371 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine) 0 0.021204 44 LMOMA output 1 CAETHG_1270 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine) 0 0.021204 45 LMOMA output 1 CAETHG_3924 O-ribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose-5- phosphate) 0 0.021204 46 LMOMA output 2 CAETHG_2721, CAETHG_3021 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline) 0 0.021012 47 LMOMA output 2 CAETHG_2107, CAETHG_2721 Potassium absorption (K+_nar. <=> K+), phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate) 0 0.020931 48 LMOMA output 1 CAETHG_2721 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate) 0 0.020928 49 LMOMA output 2 CAETHG_2475, CAETHG_3021 dGTP triphosphohydrolase (H2O + dGTP -> H+ + deoxyguanosine + triphosphate), L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline) 0 0.020073 50 LMOMA output 1 CAETHG_3021 L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline) 0 0.020058

Example 7.

This example describes perturbations to improve 1,3-butanediol production in Wood-Ljungdahl microorganisms. Metabolic modeling experiments were performed as described in Example 1.

The production of 1,3-butanediol in Wood-Ljungdahl microorganisms is described, for example, in WO 2017/0066498. To model the production of 1,3-butanediol, the following pathway was used herein: 2,0 acetyl-CoA^CoA+acetoacetyl-CoA; NADPH+H++acetoacetyl-CoA^NADP+(R)-3hydroxybutyryl-CoA; phosphate+(R)-3-hydroxybutyryl-CoA^CoA+(R)-3-hydroxybutyrylphosphate; ADP+(R)-3-hydroxybutyrylphosphate^ATP+(R)-3-hydroxybutyrate; (R)-3-hydroxybutyrate+reduced ferredoxin^oxidized ferredoxin+(R)-3-hydroxybutyraldehyde; NADPH+H++(R)-3hydroxybutyraldehyde^NADP+13BDO; NADH+H++(R)-3-hydroxybutyraldehyde^NAD+13BDO; 13BDO^13BDO_adv.

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ft Methodology About co ABOUT Disturbed genes Disturbed reactions Minimum FVA output Compliance score 1 BPCY - FBA 4 CAETHG_2751, CAETHG_2909, CAETHG_3293, CAETHG_3358 Citramalate synthase (H2O + pyruvate + acetyl-CoA <=> CoA + citramalate), ATP:pyruvate-orthophosphate phosphotransferase (ATP + phosphate + pyruvate + H+ -> PPi + AMP + phosphoenolpyruvate), cysteine desulfhydrase (H2O + L-cysteine <=> NH3 + pyruvate + H2S), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0.05315 0.005908 2 BPCY - FBA 3 CAETHG_2909, CAETHG_3293, CAETHG_3358 ATP: pyruvate orthophosphate phosphotransferase (ATP + phosphate + pyruvate + H+ -> PPi + AMP + phosphoenolpyruvate), cysteine desulfhydrase (H2O + L-cysteine <=> NH3 + pyruvate + H2S), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0.05193 0.005808 3 BPCY - FBA 3 CAETHG_2751, CAETHG_2909, CAETHG_3358 Citramalate synthase (H2O + pyruvate + acetyl-CoA <=> CoA + citramalate), ATP:pyruvate-orthophosphate phosphotransferase (ATP + phosphate + pyruvate + H+ -> PPi + AMP + phosphoenolpyruvate), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0.05085 0.005774 4 BPCY - FBA 3 CAETHG_2751, CAETHG_2909, CAETHG_3359 Citramalate synthase (H2O + pyruvate + acetyl-CoA <=> CoA + citramalate), ATP: pyruvate-orthophosphate phosphotransferase (ATP + phosphate + pyruvate + H+ -> PPi + AMP + phosphoenolpyruvate), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0.05085 0.005774 5 BPCY - FBA 3 CAETHG_2909, CAETHG_3358, CAETHG_0498 ATP: pyruvate orthophosphate phosphotransferase (ATP + phosphate + pyruvate + H+ -> PPi + AMP + phosphoenolpyruvate), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0.05054 0.005734 6 BPCY - FBA 2 CAETHG_2909, CAETHG_3359 ATP: pyruvate orthophosphate phosphotransferase (ATP + phosphate + pyruvate + H+ -> PPi + AMP + phosphoenolpyruvate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0.04960 0.005672 7 BPCY - FBA 2 CAETHG_2909, CAETHG_3358 ATP: pyruvate orthophosphate phosphotransferase (ATP + phosphate + pyruvate + H+ -> PPi + AMP + phosphoenolpyruvate), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0.04960 0.005672 8 BPCY 3 CAETHG_2751, Citramalate synthase (H2O + pyruvate + acetyl-CoA <=> CoA + 0.04193 0.004892 -FBA CAETHG_3293, CAETHG_3358 citramalate), cysteine desulfhydrase (H2O + L-cysteine <=> NH3 + pyruvate + H2S), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 9 BPCY - FBA 2 CAETHG_3293, CAETHG_3359 Cysteine desulfhydrase (H2O + L-cysteine <=> NH3 + pyruvate + H2S), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0.04068 0.004788 10 BPCY - FBA 2 CAETHG_3293, CAETHG_3358 Cysteine desulfhydrase (H2O + L-cysteine <=> NH3 + pyruvate + H2S), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0.04068 0.004788 eleven BPCY - FBA 2 CAETHG_2751, CAETHG_3359 Citramalate synthase (H2O + pyruvate + acetyl-CoA <=> CoA + citramalate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0.03923 0.004684 12 BPCY - FBA 2 CAETHG_2751, CAETHG_3358 Citramalate synthase (H2O + pyruvate + acetyl-CoA <=> CoA + citramalate), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0.03923 0.004684 13 BPCY - FBA 2 CAETHG_3359, CAETHG_0498 ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), cystathionine beta-lyase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0.03904 0.004667 14 BPCY - FBA 2 CAETHG_3358, CAETHG_0498 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0.03904 0.004667 15 BPCY - FBA 1 CAETHG_3359 ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0.03795 0.004575 16 BPCY - FBA 1 CAETHG_3358 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0.03795 0.004575

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Example 8.

This example describes perturbations to improve 2,3-butanediol production in Wood-Ljungdahl microorganisms. Metabolic modeling experiments were performed as described in Example 1. 2,3-Butanediol is a native product of at least some Wood-Ljungdahl microorganisms. _______________________________________________________________

ft Methodology Oh co ABOUT Disturbed genes Disturbed reactions Minimum FVA output Compliance score 1 LMOMA output 5 CAETHG_1147, CAETHG_2753, CAETHG_3359, CAETHG_351O, CAETHG_O9O9 Lactate dehydrogenase (NAD + D-lactate <=> NADH + pyruvate + H+), isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), ATP: acetate phosphotransferase (ΑΤΦ + H+ + propionate -- > ADP + propionyl phosphate), 2,6 diaminoheptanedioate: 2-oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <- 2oxoglutarate + 1_1_-2,6-diaminopimelate), prephenate: NAD + oxidoreductase (decarboxylating) (NAD + prephenate > NADH + CO2 + p-hydroxyphenylpyruvate) 0.033681 0.049774 2 LMOMA output 4 CAETHG_1147, CAETHG_2753, CAETHG_3359, CAETHG_351O Lactate dehydrogenase (NAD + D-lactate <=> NADH + pyruvate + H+), isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), ATP: acetate phosphotransferase (ΑΤΦ + H+ + propionate -- > ADP + propionyl phosphate), 2,6- 0.033681 0.049768

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diaminoheptanedioate:2-oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <- 2oxoglutarate + u_-2,6-diaminopimelate) 3 LMOMA output 4 CAETHG_0248, CAETHG_2753, CAETHG_3359, CAETHG_351O Reversible transport of L-lactate in symport with protons (H+_nar. + E-lactate_nar. <=> H+ + L-lactate), isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), 2,6diaminoheptanedioate:2-oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <- 2oxoglutarate + i_-2,6-diaminopimelate) 0.033681 0.049768 4 LMOMA output 3 CAETHG_0248, CAETHG_3359, CAETHG_351O Reversible transport of L-lactate in symport with protons (H+_nar. + E-lactate_nar. <=> H+ + L-lactate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), 2.6 -diaminoheptanedioate:2oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <- 2-oxoglutarate + LL-2,6- diaminopimelate) 0.03068 0.04884 5 LMOMA output 4 CAETHG_0248, CAETHG_2721, CAETHG_3327, CAETHG_3359 Reversible transport of L-lactate in symport with protons (H+_nar. + E-lactate_nar. <=> H+ + L-lactate), phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), ABC phosphate transporter permease protein (PPi + H+ --> PP|_nar. + H+_nar.), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.026026 6 LMOMA output 4 CAETHG_0248, CAETHG_3359, CAETHG_3924, CAETHG_0476 Reversible transport of L-lactate in symport with protons (H+_nar. + E-lactate_nar. <=> H+ + L-lactate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), O-ribose -1,5-phosphomutase (ribose-1-phosphate <=> ribose-5-phosphate), S- aminomethyldihydrolipoylprotein:(65)-tetrahydrofolate (tetrahydrofolate + S-aminomethyldihydrolipoylprotein <=> NH3 + 5-10-methylenetetrahydrofolate + dihydrolipoylprotein) 0 0.02553 7 LMOMA output 4 CAETHG_0248, CAETHG_3359, CAETHG_3924, CAETHG_0475 Reversible transport of L-lactate in symport with protons (H+_nar. + E-lactate_nar. <=> H+ + L-lactate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), O-ribose -1,5-phosphomutase (ribose-1-phosphate <=> ribose-5-phosphate), S- aminomethyldihydrolipoylprotein:(65)-tetrahydrofolate (tetrahydrofolate + S-aminomethyldihydrolipoylprotein <=> NH3 + 5-10-methylenetetrahydrofolate + dihydrolipoylprotein) 0 0.02553 8 LMOMA output 4 CAETHG_0248, CAETHG_3359, CAETHG_3924, CAETHG_0474 Reversible transport of L-lactate in symport with protons (H+_nar. + E-lactate_nar. <=> H+ + L-lactate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), O-ribose -1,5-phosphomutase (ribose-1-phosphate <=> ribose-5-phosphate), glycine: lipoylprotein oxidoreductase (decarboxylating and acceptor-aminomethylating) (glycine + H+ + lipoylprotein -> CO2 + Saminomethyldihydrolipoylprotein) 0 0.02553 9 LMOMA output 4 CAETHG_127O, CAETHG_0248, CAETHG_2753, CAETHG_3359 AMP: pyrophosphate phosphoribosyltransferase (PΡί + AMP <=> PRPP + adenine), reversible transport of L-lactate in symport with protons (H+_nar. + E-lactate_nar. <=> H+ + L-lactate), isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0 0.025452 10 Exit - 4 CAETHG_0248, Reversible transport of L-lactate in symport with protons 0 0.025452

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LMOMA CAETHG_2753, CAETHG_3359, CAETHG_3924 (H+_nar. + E-lactate_nar. <=> H+ + L-lactate), isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), O-ribose-1,5phosphomutase (ribose-1-phosphate <=> ribose-5-phosphate) eleven LMOMA output 4 CAETHG_O248, CAETHG_3359, CAETHG_3924, CAETHG_O498 Reversible transport of L-lactate in symport with protons (H+_nar. + E-lactate_nar. <=> H+ + L-lactate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), O-ribose -1,5-phosphomutase (ribose-1-phosphate <=> ribose-5-phosphate), cystathionine beta synthase (L-serine + homocysteine <=> H2O + cystathionine) 0 0.025422 12 LMOMA output 3 CAETHG_1371, CAETHG_O248, CAETHG_3359 5'-nucleotidase (dUMP) (H2O + dUMP -> phosphate + H+ + deoxyuridine), reversible transport of L-lactate in symport with protons (H+_nar. + E-lactate_nar. <=> H+ + L-lactate) , ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.025412 13 LMOMA output 3 CAETHG_1147, CAETHG_3359, CAETHG_3924 Lactate dehydrogenase (NAD + D-lactate <=> NADH + pyruvate + H+), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), O-ribose-1,5-phosphomutase (ribose-1- phosphate <=> ribose-5-phosphate) 0 0.025412 14 LMOMA output 3 CAETHG_0160, CAETHG_O248, CAETHG_3359 Reversible transport of L-lactate in symport with protons (H+_nar. + E-lactate_nar. <=> H+ + L-lactate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.025412 15 LMOMA output 3 CAETHG_O248, CAETHG_3359, CAETHG_3924 Reversible transport of L-lactate in symport with protons (H+_nar. + E-lactate_nar. <=> H+ + L-lactate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), O-ribose -1,5-phosphomutase (ribose-1-phosphate <=> ribose-5-phosphate) 0 0.025412 16 LMOMA output 3 CAETHG_O248, CAETHG_2721, CAETHG_3359 Reversible transport of L-lactate in symport with protons (H+_nar. + E-lactate_nar. <=> H+ + L-lactate), phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.02517 17 LMOMA output 3 CAETHG_1147, CAETHG_2753, CAETHG_3359 Lactate dehydrogenase (NAD + D-lactate <=> NADH + pyruvate + H+), isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), ATP: acetate phosphotransferase (ATP + H+ + propionate -- > ADP + propionyl phosphate) 0 0.024914 18 LMOMA output 3 CAETHG_O248, CAETHG_2753, CAETHG_3359 Reversible transport of L-lactate in symport with protons (H+_nar. + E-lactate_nar. <=> H+ + L-lactate), isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0 0.024914 19 LMOMA output 3 CAETHG_O248, CAETHG_3299, CAETHG_3359 Reversible transport of L-lactate in symport with protons (H+_nar. + E-lactate_nar. <=> H+ + L-lactate), 2-deoxy-Oribose-5-phosphate acetaldehyde lyase (deoxyribose-5- phosphate <=> acetaldehyde + glyceraldehyde-3-phosphate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.0249 20 LMOMA output 4 CAETHG_O248, CAETHG_2475, CAETHG_3164, CAETHG_3359 Reversible transport of L-lactate in symport with protons (H+_nar. + E-lactate_nar. <=> H+ + L-lactate), dGTP triphosphohydrolase (H2O + dGTP --> H+ + deoxyguanosine + triphosphate), UMP: pyrophosphate phosphoribosyltransferase ( uracil + PRPP -> PPi + UMP), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0 0.0249 21 LMOMA output 3 CAETHG_O248, CAETHG_2475, Reversible transport of L-lactate in symport with protons (H+_nar. + E-lactate_nar. <=> Н+ + L-lactate), dGTP- 0 0.024882

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CAETHG_3359 triphosphohydrolase (H2O + dGTP -> H+ + deoxyguanosine + triphosphate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 22 LMOMA output 3 CAETHG_1607, CAETHG_0248, CAETHG_3359 5-aminomethyldihydrolipoylprotein:(65)-tetrahydrofolate (tetrahydrofolate + S-aminomethyldihydrolipoylprotein <=> NH3 + 5-10-methylenetetrahydrofolate + dihydrolipoylprotein), reversible transport of L-lactate in symport with protons (H+_nar. + E-lactate_nar. <=> H+ + Llactate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.024808 23 LMOMA output 3 CAETHG_0248, CAETHG_3359, CAETHG_0475 Reversible transport of L-lactate in symport with protons (H+_nar. + E-lactate_nar. <=> H+ + L-lactate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), S- aminomethyldihydrolipoylprotein:(65)-tetrahydrofolate (tetrahydrofolate + S-aminomethyldihydrolipoylprotein <=> NH3 + 5-10-methylenetetrahydrofolate + dihydrolipoylprotein) 0 0.024808 24 LMOMA output 3 CAETHG_0248, CAETHG_3359, CAETHG_0474 Reversible transport of L-lactate in symport with protons (H+_nar. + E-lactate_nar. <=> H+ + L-lactate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), glycine: lipoylprotein oxidoreductase (decarboxylating and acceptor-aminomethylating) (glycine + H+ + lipoylprotein -> CO2 + Saminomethyldihydrolipoylprotein) 0 0.024808 25 LMOMA output 3 CAETHG_0248, CAETHG_3327, CAETHG_3359 Reversible transport of L-lactate in symport with protons (H+_nar. + E-lactate_nar. <=> H+ + L-lactate), permease protein ABC phosphate transporter (PPi + H+ -> PP|_nar. + H+ _nar.), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.024802 26 LMOMA output 3 CAETHG_0248, CAETHG_3359, CAETHG_0473 Reversible transport of L-lactate in symport with protons (H+_nar. + E-lactate_nar. <=> H+ + L-lactate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), glycine: lipoylprotein oxidoreductase (decarboxylating and acceptor-aminomethylating) (glycine + H+ + lipoylprotein -> CO2 + Saminomethyldihydrolipoylprotein) 0 0.024788 27 LMOMA output 3 CAETHG_1147, CAETHG_3359, CAETHG_0498 Lactate dehydrogenase (NAD + D-lactate <=> NADH + pyruvate + H+), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), cystathionine beta synthase (Lserine + homocysteine <=> H2O + cystathionine) 0 0.024756 28 LMOMA output 3 CAETHG_0248, CAETHG_3164, CAETHG_3359 Reversible transport of L-lactate in symport with protons (H+_nar. + E-lactate_nar. <=> H+ + L-lactate), UMP: pyrophosphate phosphoribosyltransferase (uracil + PRPP --> PPi + UMP), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.024426 29 LMOMA output 2 CAETHG_1147, CAETHG_3359 Lactate dehydrogenase (NAD + D-lactate <=> NADH + pyruvate + H+), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0 0.024408 thirty LMOMA output 2 CAETHG_0248, CAETHG_3359 Reversible transport of L-lactate in symport with protons (H+_nar. + E-lactate_nar. <=> H+ + L-lactate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.024408 31 LMOMA output 4 CAETHG_0160, CAETHG_0248, CAETHG_2753, Reversible transport of L-lactate in symport with protons (H+_nar. + E-lactate_nar. <=> H+ + L-lactate), isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 0 0.013792

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CAETHG_3327 2-oxoglutarate + H+), ABC phosphate transporter permease protein (PPi + H+ -> PPi_Hap. + H+_nar.) 32 LMOMA output 4 CAETHG_0248, CAETHG_2753, CAETHG_3327, CAETHG_3924 Reversible transport of L-lactate in symport with protons (H+_nar. + E-lactate_nar. <=> H+ + L-lactate), isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), ABC phosphate transporter permease protein (PPi + H+ --> PP|_nar. + H+_nar.), O-ribose-1,5phosphomutase (ribose-1-phosphate <=> ribose-5-phosphate) 0 0.013792 33 LMOMA output 4 CAETHG_127O, CAETHG_0248, CAETHG_2753, CAETHG_3327 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), reversible transport of L-lactate in symport with protons (H+_nar. + E-lactate_nar. <=> H+ + L-lactate), isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), permease protein ABC phosphate transporter (PPi + H+ --> PP|_nar. + H+_nar.) 0 0.013792 34 LMOMA output 4 CAETHG_2753, CAETHG_3359, CAETHG_3924, CAETHG_0498 Isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), O-ribose-1,5phosphomutase (ribose-1- phosphate <=> ribose-5-phosphate), cystathionine beta synthase (L-serine + homocysteine <=> H2O + cystathionine) 0 0.013708 35 LMOMA output 3 CAETHG_2753, CAETHG_3359, CAETHG_3924 Isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), O-ribose-1,5phosphomutase (ribose-1- phosphate <=> ribose-5-phosphate) 0 0.0137 36 LMOMA output 3 CAETHG_127O, CAETHG_2753, CAETHG_3359 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.0137 37 LMOMA output 3 0, CAETHG_2753, CAETHG_3359 Acetyl-CoAzharbondioxide ligase (ADP-forming) (ATP + acetyl-CoA + H2CO3 -> ADP + phosphate + H+ + malonylCoA), isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0 0.013628 38 LMOMA output 2 CAETHG_3359, CAETHG_351O ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), 2,6-diaminoheptanedioate: 2oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <- 2-oxoglutarate + LL-2,6- diaminopimelate) 0.03068 0.013564 39 LMOMA output 2 CAETHG_2721, CAETHG_3359 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.01353 40 LMOMA output 2 CAETHG_2753, CAETHG_3359 Isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0 0.013514 41 LMOMA output 2 CAETHG_0248, CAETHG_2753 Reversible transport of L-lactate in symport with protons (H+_nar. + E-lactate_nar. <=> H+ + L-lactate), isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+) 0 0.011978 42 LMOMA output 2 CAETHG_2753, CAETHG_3924 Isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), O-ribose-1,5-phosphomutase (ribose-1phosphate <=> ribose-5-phosphate) 0 0.011892 43 LMOMA output 2 CAETHG_0160, CAETHG_2753 Isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+) 0 0.011892 44 LMOMA output 2 CAETHG_2753, CAETHG_0498 Isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), cystathionine beta synthase (L-serine + 0 0.011848 45 46 LMOMA output LMOMA output 2 2 CAETHG_2753, CAETHG_3327 CAETHG_2721, CAETHG_2753 homocysteine <=> H2O + cystathionine) Isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), ABC phosphate transporter permease protein (PPi + H+ --> PP|_nar. + H+_nar.) Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+) 0 0 0.01184 0.011832 47 LMOMA output 1 CAETHG_2753 Isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+) 0 0.011772

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Example 9.

This example describes disturbances to improve 2-butanol production in Wood-Ljungdahl microorganisms. Metabolic modeling experiments were performed as described in example 1. The production of 2-butanol in Wood-Ljungdahl microorganisms is described, for example, in WO 2013/185123. To model the production of 2-butanol, the following pathway was used in this paper: NADH+H++(R)-acetoin^NAD+meso-2,3-butanediol; meso-2,3-butanediol^H2O+MEK;

MEK+NADPH+H+^2-butanol+NADP; 2-butanol^2-butanol_nar._______________________

ft Methodology Oh co ABOUT Disturbed genes Disturbed reactions eN OS n ^S Minimum FVA output EN N 2 F o X L5 f -About SP SO With; go n With; * O go o o neck 1 LMOMA output 4 CAETHG_2721, CAETHG_3924, CAETHG_0498, CAETHG_0686 Phosphoenolpyruvate carboxykinase (PPCK) (ΑΤΦ + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), Dribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose-5phosphate), cystathionine beta-lyase (H2O + cystathionine —> NH3 + pyruvate + homocysteine), L-threonine acetaldehyde lyase (L-threonine --> glycine + acetaldehyde) 0 0.020756 2 LMOMA output 4 CAETHG_1371, CAETHG_2721, CAETHG_0498, CAETHG_0686 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine), phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), cystathionine beta-lyase (H2O + cystathionine -> NH3 + pyruvate + homocysteine), Lthreonine acetaldehyde lyase (L-threonine --> glycine + acetaldehyde) 0 0.020756 3 LMOMA output 4 CAETHG_127O, CAETHG_2721, CAETHG_0498, CAETHG_0686 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), phosphoenolpyruvate carboxykinase (PPKK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), cystathionine beta-lyase (H2O + cystathionine -> NH3 + pyruvate + homocysteine), Lthreonine acetaldehyde lyase (L-threonine --> glycine + acetaldehyde) 0 0.020756 4 LMOMA output 4 CAETHG_1371, CAETHG_2721, CAETHG_3293, CAETHG_0686 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine), phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), cysteine desulfhydrase (H2O + L- 0 0.02064

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cysteine <=> NH3 + pyruvate + H2S), Lthreonine acetaldehyde lyase (L-threonine --> glycine + acetaldehyde) 5 LMOMA output 4 CAETHG_127O, CAETHG_2721, CAETHG_3293, CAETHG_0686 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), phosphoenolpyruvate carboxykinase (PPKK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), cysteine desulfhydrase (H2O + Lcysteine <=> NH3 + pyruvate + H2S), L- Threonine acetaldehyde lyase (L-threonine --> glycine + acetaldehyde) 0 0.02064 6 LMOMA output 4 CAETHG_1371, CAETHG_2721, CAETHG_3O21, CAETHG_0686 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine), phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), L-arginine iminohydrolase (H2O + Larginine <= > NH3 + citrulline), L-threonine acetaldehyde lyase (L-threonine --> glycine + acetaldehyde) 0 0.020476 7 LMOMA output 4 CAETHG_2721, CAETHG_3O21, CAETHG_3924, CAETHG_0686 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ --> ADP + CO2 + phosphoenolpyruvate), L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), 0-ribose-1,5-phosphomutase (ribose-1- phosphate <=> ribose-5-phosphate), L-threonine acetaldehyde lyase (Lthreonine --> glycine + acetaldehyde) 0 0.020476 8 LMOMA output 3 CAETHG_1371, CAETHG_2721, CAETHG_0686 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine), phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), L-threonine acetaldehyde lyase (Lthreonine --> glycine + acetaldehyde) 0 0.020468 9 LMOMA output 3 CAETHG_127O, CAETHG_2721, CAETHG_0686 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), L-threonine acetaldehyde lyase (Lthreonine --> glycine + acetaldehyde) 0 0.020468 10 LMOMA output 3 CAETHG_2721, CAETHG_3924, CAETHG_0686 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), Dribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose-5phosphate), L-threonine acetaldehyde lyase (L-threonine -> glycine + acetaldehyde) 0 0.020468 eleven LMOMA output 4 CAETHG_2721, CAETHG_3924, CAETHG_0498, CAETHG_0686 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), Dribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose-5phosphate), cystathionine beta-lyase (H2O + cystathionine -> NH3 + pyruvate + homocysteine), L-threonine acetaldehyde lyase (L-threonine --> glycine + acetaldehyde) 0 0.020756

Example 10.

This example describes disturbances to improve 2-hydroxyisobutyric acid production in Wood-Ljungdahl microorganisms. Metabolic modeling experiments were performed as described in example 1. The production of 2-hydroxyisobutyric acid in WoodLjungdahl microorganisms is described, for example, in WO 2017/0066498.

To model the production of 2-hydroxyisobutyric acid in lines 1-40 below, the following path was used: 2.0 acetyl-CoA—CoA+acetoacetyl-CoA; NADH+H++acetoacetyl-CoA—NAD+(S)-3hydroxybutyryl-CoA; (S)-3-hydroxybutyryl-CoA—2HIB-CoA; 2H1B-CoA+H ₂ O—2hib+CoA;

2hib—2hib_нαр.

To model the production of 2-hydroxyisobutyric acid in lines 41-93 below, the following path was used: 2.0 acetyl-CoA—CoA+acetoacetyl-CoA; NADH+H++acetoacetyl-CoA—NAD+(S)-3hydroxybutyryl-CoA; (S)-3-hydroxybutyryl-CoA—2HIB-CoA; 2HIBCoA+ADP+phosphate—2hib+ATP+CoA; 2hib—2hib_nar.

To model the production of 2-hydroxyisobutyric acid in lines 94-103 below, the following path was used: 2.0 acetyl-CoA—CoA+acetoacetyl-CoA; NADH+H++acetoacetyl-CoA—NAD(S)3-hydroxybutyryl-CoA; (S)-3-hydroxybutyryl-CoA—2HIB-CoA; 2HIB-CoA+acetate—2hib+acetylCoA; 2hib—2hib_nar.

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ft Methodology Number of violated Disturbed genes Disturbed reactions Minimum FVA output OS n ^S EN “ 2 F o T L5 f -About joint venture with With; pz n With; * O P5 O O Sh s i 1 LMOMA output 4 CAETHG_2721, CAETHG_2932, CAETHG_3359, CAETHG_0498 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), alpha-acetolactate decarboxylase (ALCTT --> CO2 + (R)acetoin), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), cystathionine beta-lyase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0 0.074552 2 LMOMA output 4 CAETHG_2721, CAETHG_2932, CAETHG_3358, CAETHG_0498 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), alpha-acetolactate decarboxylase (ALCTT --> CO2 + (R)acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0 0.074552 3 LMOMA output 3 CAETHG_2721, CAETHG_2932, CAETHG_3358 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), alpha-acetolactate decarboxylase (ALCTT --> CO2 + (R)acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.071296 4 LMOMA output 4 CAETHG_0160, CAETHG_2932, CAETHG_3358, CAETHG_0498 N-ribosylnicotinamide: orthophosphate ribosyltransferase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), alpha-acetolactate decarboxylase (ALCTT --> CO2 + (K)-acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), cystathionine beta-lyase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0 0.05776 5 LMOMA output 4 CAETHG_2475, CAETHG_2932, CAETHG_3358, CAETHG_0498 dGTP triphosphohydrolase (H2O + dGTP -> H+ + deoxyguanosine + triphosphate), alpha acetolactate decarboxylase (ALCTT -> CO2 + (R)acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), cystathionine beta-lyase 0 0.055144

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(H2O + cystathionine --> NH3 + pyruvate + homocysteine) 6 LMOMA output 3 CAETHG_2932, CAETHG_3358, CAETHG_0686 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (R)acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate), L- Threonine acetaldehyde lyase (L-threonine -> glycine + acetaldehyde) 0 0.055008 7 LMOMA output 3 CAETHG_2932, CAETHG_3358, CAETHG_0498 Alpha-acetolactate decarboxylase (ALCTT --> CO2 + (R)acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0 0.054724 8 LMOMA output 4 CAETHG_21O7, CAETHG_2932, CAETHG_3358, CAETHG_3924 Potassium absorption (K+_nar. <=> K+), alpha acetolactate decarboxylase (ALCTT -> CO2 + (R)acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), O-ribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose -5-phosphate) 0 0.054364 9 LMOMA output 4 CAETHG_1371, CAETHG_21O7, CAETHG_2932, CAETHG_3358 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine), potassium uptake (K+_nar <=> K+), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (Rj-acetoin), phosphate transacetylase (phosphate + acetylCoA + H+ <=> CoA + acetylphosphate) 0 0.054364 10 LMOMA output 3 CAETHG_2932, CAETHG_3358, CAETHG_3924 Alpha-acetolactate decarboxylase (ALCTT --> CO2 + (R)acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), O-ribose-1,5-phosphomutase (ribose-1-phosphate < => ribose 5-phosphate) 0 0.05436 eleven LMOMA output 3 CAETHG_127O, CAETHG_2932, CAETHG_3358 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), alpha-acetolactate decarboxylase (ALCTT --> CO2 + (P)-acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate) 0 0.05436 12 LMOMA output 3 CAETHG_1371, CAETHG_2932, CAETHG_3358 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (R)acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate ) 0 0.05436 13 LMOMA output 3 CAETHG_0160, CAETHG_2932, CAETHG_3358 N-ribosylnicotinamide: orthophosphate ribosyltransferase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), alpha-acetolactate decarboxylase (ALCTT --> CO2 + (P)-acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.05436 14 LMOMA output 3 CAETHG_2932, CAETHG_3299, CAETHG_3358 Alpha-acetolactate decarboxylase (ALCTT --> CO2 + (R)acetoin), 2-deoxy-O-ribose-5- phosphate acetaldehyde lyase (deoxyribose-5-phosphate <=> acetaldehyde + glyceraldehyde-3-phosphate), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.051804 15 LMOMA output 3 CAETHG_2475, CAETHG_2932, CAETHG_3358 dGTP triphosphohydrolase (H2O + dGTP -> H+ + deoxyguanosine + triphosphate), alpha acetolactate decarboxylase (ALCTT -> CO2 + (R)acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate) 0 0.051796 16 LMOMA output 3 CAETHG_2932, CAETHG_3021, CAETHG_3358 Alpha-acetolactate decarboxylase (ALCTT --> CO2 + (R)acetoin), L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.051492 17 LMOMA output 4 CAETHG_21O7, CAETHG_2932, CAETHG_3164, CAETHG_3358 Potassium absorption (K+_nar. <=> K+), alpha acetolactate decarboxylase (ALCTT -> CO2 + (R)acetoin), UMP: pyrophosphate phosphoribosyltransferase (uracil + PRPP -> PPi + UMP), phosphate transacetylase 0 0.051376

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(phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 18 LMOMA output 3 CAETHG_2107, CAETHG_2932, CAETHG_3358 Potassium absorption (K+_nar. <=> K+), alpha acetolactate decarboxylase (ALCTT -> CO2 + (R)acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate) 0 0.051368 19 LMOMA output 2 CAETHG_2932, CAETHG_3358 Alpha-acetolactate decarboxylase (ALCTT --> CO2 + (R)acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.051364 20 LMOMA output 2 CAETHG_2932, CAETHG_3359 Alpha-acetolactate decarboxylase (ALCTT --> CO2 + (R)acetoin), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0 0.051364 21 LMOMA output 3 CAETHG_2751, CAETHG_3358, CAETHG_0498 Citramalate synthase (H2O + pyruvate + acetyl-CoA <=> CoA + citramalate), phosphate transacetylase (phosphate + acetylCoA + H+ <=> CoA + acetylphosphate), cystathionine betaliase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0 0.047452 22 LMOMA output 3 CAETHG_3021, CAETHG_3358, CAETHG_0498 L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0 0.045856 23 LMOMA output 3 CAETHG_2475, CAETHG_3358, CAETHG_0498 dGTP triphosphohydrolase (H2O + dGTP -> H+ + deoxyguanosine + triphosphate), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), cystathionine beta-lyase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0 0.04582 24 LMOMA output 2 CAETHG_3359, CAETHG_0498 ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0 0.045768 25 LMOMA output 2 CAETHG_3358, CAETHG_0498 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0 0.045768 26 LMOMA output 2 CAETHG_3359, CAETHG_3924 ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), O-ribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose-5-phosphate) 0 0.04472 27 LMOMA output 2 CAETHG_1371, CAETHG_3359 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0 0.04472 28 LMOMA output 2 CAETHG_1270, CAETHG_3359 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.04472 29 LMOMA output 2 CAETHG_0160, CAETHG_3359 N-ribosylnicotinamide: opτoφocφaτpibosyltransferase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.04472 thirty LMOMA output 2 CAETHG_3359, CAETHG_0686 ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), L-threonine acetaldehyde lyase (L-threonine -> glycine + acetaldehyde) 0 0.04366 31 LMOMA output 2 CAETHG_3021, CAETHG_3359 L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0 0.043384 32 LMOMA output 2 CAETHG_2107, CAETHG_3359 Potassium absorption (K+_nar. <=> K+), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0 0.0433

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33 LMOMA output 1 CAETHG_3358 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.043296 34 LMOMA output 1 CAETHG_3359 ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.043296 35 LMOMA output 1 CAETHG_1371 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine) 0 0.020432 36 LMOMA output 1 CAETHG_0160 N-ribosylnicotinamide:orthophosphate ribosyltransferase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate) 0 0.020432 37 LMOMA output 1 CAETHG_127O AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine) 0 0.020432 38 LMOMA output 1 CAETHG_3924 O-ribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose5-phosphate) 0 0.020432 39 LMOMA output 1 CAETHG_2721 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ --> ADP + CO2 + phosphoenolpyruvate) 0 0.020356 40 LMOMA output 1 CAETHG_3O21 L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline) 0 0.020028 41 BPCY- FBA 1 CAETHG_3358 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0.21671 0.048129 42 BPCY- FBA 1 CAETHG_3359 ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0.21671 0.048129 43 BPCY- FBA 1 CAETHG_29O9 ATP: pyruvate orthophosphate phosphotransferase (ATP + phosphate + pyruvate + H+ -> PPi + AMP + phosphoenolpyruvate) 0.21241 0.000573 44 LMOMA output 4 CAETHG_0234, CAETHG_2751, CAETHG_3359, CAETHG_351O 4,5-dihydro-4-oxo-5-imidazolepropanoate hydrolyase (4imidazolone-5-propanoate <=> H2O + urocanate), citramalate synthase (H2O + pyruvate + acetyl-CoA <=> CoA + citramalate), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), 2,6diaminoheptanedioate:2-oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2oxoglutarate + EE-2,6-diaminopimelate) 0.21241 0.11296 45 LMOMA output 4 CAETHG_O233, CAETHG_2751, CAETHG_3359, CAETHG_351O 4-imidazolone-5-propanoate amidohydrolase (H2O + 4-imidazolone-5-propanoate -> N-formimino-E-glutamate), citramalate synthase (H2O + pyruvate + acetyl-CoA <=> CoA + citramalate), ATP: acetate phosphotransferase (ATP + H + + propionate --> ADP + propionyl phosphate), 2,6diaminoheptanedioate:2-oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2oxoglutarate + EE-2,6-diaminopimelate) 0.21058 0.11296 46 LMOMA output 2 CAETHG_3358, CAETHG_351O Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate), 2,6-diaminoheptanedioate:2oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6diaminopimelate) 0.21058 0.111576 47 LMOMA output 2 CAETHG_3359, CAETHG_351O ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), 2,6-diaminoheptanedioate: 2oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6diaminopimelate) 0.21544 0.111576 48 LMOMA output 4 CAETHG_2721, CAETHG_2753, CAETHG_3358, CAETHG_0498 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate), 0.21528 0.104448

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cystathionine beta-lyase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 49 LMOMA output 3 CAETHG_2721, CAETHG_3358, CAETHG_0498 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0.21528 0.104424 50 LMOMA output 4 CAETHG_2721, CAETHG_3021, CAETHG_3358, CAETHG_3924 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ --> ADP + CO2 + phosphoenolpyruvate), L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), O-ribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose-5-phosphate) 0.21528 0.102516 51 LMOMA output 3 CAETHG_1371, CAETHG_2721, CAETHG_3358 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine), phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate) 0.21221 0.102476 52 LMOMA output 3 CAETHG_2721, CAETHG_3358, CAETHG_3924 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), O-ribose-1,5-phosphomutase (ribose- 1-phosphate <=> ribose-5-phosphate) 0.21204 0.102476 53 LMOMA output 3 CAETHG_127O, CAETHG_2721, CAETHG_3358 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0.21204 0.102464 54 LMOMA output 3 CAETHG_2721, CAETHG_3021, CAETHG_3358 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ --> ADP + CO2 + phosphoenolpyruvate), L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0.21204 0.102348 55 LMOMA output 3 CAETHG_2721, CAETHG_2753, CAETHG_3358 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0.21204 0.102324 56 LMOMA output 3 CAETHG_21O7, CAETHG_2721, CAETHG_3358 Potassium absorption (K+_nar. <=> K+), phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate) 0.21353 0.102304 57 LMOMA output 2 CAETHG_2721, CAETHG_3358 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate) 0.21353 0.1023 58 LMOMA output 2 CAETHG_2721, CAETHG_3359 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0.21241 0.1023 59 LMOMA output 3 CAETHG_1371, CAETHG_2932, CAETHG_3358 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (R)acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate ) 0.21241 0.090748

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60 LMOMA output 3 CAETHG_1270, CAETHG_2932, CAETHG_3358 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), alpha-acetolactate decarboxylase (ALCTT --> CO2 + (P)-acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0.21171 0.090656 61 LMOMA output 2 CAETHG_2932, CAETHG_3359 Alpha-acetolactate decarboxylase (ALCTT --> CO2 + (R)acetoin), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0.21171 0.089548 62 LMOMA output 2 CAETHG_2932, CAETHG_3358 Alpha-acetolactate decarboxylase (ALCTT --> CO2 + (R)acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0.21171 0.089548 63 LMOMA output 3 CAETHG_2475, CAETHG_3358, CAETHG_0686 dGTP triphosphohydrolase (H2O + dGTP -> H+ + deoxyguanosine + triphosphate), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), L-threonine acetaldehyde lyase (L-threonine -> glycine + acetaldehyde) 0.21646 0.083936 64 LMOMA output 2 CAETHG_3359, CAETHG_0686 ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), L-threonine acetaldehyde lyase (L-threonine -> glycine + acetaldehyde) 0.21753 0.083768 65 LMOMA output 2 CAETHG_3358, CAETHG_0686 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), L-threonine acetaldehyde lyase (Lthreonine -> glycine + acetaldehyde) 0.21753 0.083768 66 LMOMA output 3 CAETHG_0160, CAETHG_3358, CAETHG_0498 N-ribosylnicotinamide:opτoφocφaτpibosyltransferase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), cystathionine beta-lyase (H2 O + cystathionine -> NH3 + pyruvate + homocysteine) 0.21753 0.082284 67 LMOMA output 3 CAETHG_2475, CAETHG_3358, CAETHG_0498 dGTP triphosphohydrolase (H2O + dGTP -> H+ + deoxyguanosine + triphosphate), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), cystathionine beta-lyase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0.21753 0.080496 68 LMOMA output 3 CAETHG_2475, CAETHG_3359, CAETHG_0498 dGTP triphosphohydrolase (H2O + dGTP -> H+ + deoxyguanosine + triphosphate), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0.21353 0.080496 69 LMOMA output 2 CAETHG_3359, CAETHG_0498 ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0.21353 0.080204 70 LMOMA output 2 CAETHG_3358, CAETHG_0498 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0.21353 0.080204 71 LMOMA output 2 CAETHG_0160, CAETHG_3359 N-ribosylnicotinamide: opτoφocφaτpibosyltransferase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0.21353 0.077112 72 LMOMA output 2 CAETHG_1371, CAETHG_3359 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0.21241 0.077112 73 LMOMA output 2 CAETHG_3359, CAETHG_3924 ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), O-ribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose-5-phosphate) 0.21236 0.077112 74 LMOMA output 2 CAETHG_1270, CAETHG_3359 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), ATP: acetate phosphotransferase (ATP + 0.21241 0.077028

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H+ + propionate -> ADP + propionyl phosphate) 75 LMOMA output 2 CAETHG_3299, CAETHG_3359 2-deoxy-O-ribose-5-phosphate acetaldehyde lyase (deoxyribose-5-phosphate <=> acetaldehyde + glyceraldehyde-3-phosphate), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0.21241 0.075868 76 LMOMA output 2 CAETHG_3021, CAETHG_3359 L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0.21241 0.075712 77 LMOMA output 2 0,CAETHG_3359 Acetyl-CoAzharbondioxide ligase (ADP-forming) (ATP + acetyl-CoA + H2CO3 --> ADP + phosphate + H+ + malonyl-CoA), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0.21241 0.075524 78 LMOMA output 2 CAETHG_2107, CAETHG_3359 Potassium absorption (K+_nar. <=> K+), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0.21241 0.075492 79 LMOMA output 2 CAETHG_2107, CAETHG_3358 Potassium absorption (K+_nar. <=> K+), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0.21241 0.075492 80 LMOMA output 2 CAETHG_3164, CAETHG_3359 UMP: pyrophosphate phosphoribosyltransferase (uracil + PRPP --> PPi + UMP), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0.21241 0.075488 81 LMOMA output 2 CAETHG_3164, CAETHG_3358 UMP: pyrophosphate phosphoribosyltransferase (uracil + PRPP --> PPi + UMP), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate) 0.21671 0.075488 82 LMOMA output 1 CAETHG_3358 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0.21671 0.075484 83 LMOMA output 1 CAETHG_3359 ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0.21241 0.075484 84 LMOMA output 2 CAETHG_1224, CAETHG_0160 L-serine ammonia lyase (L-serine -> NH3 + pyruvate), Nribosylnicotinamide:orthophosphate ribosyltransferase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate) 0 0.0213 85 LMOMA output 2 CAETHG_0160, CAETHG_2107 N-ribosylnicotinamide:opτoφocφaτpibosyltransferase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), potassium absorption (K+_nar <=> K+) 0 0.021224 86 LMOMA output 1 CAETHG_1270 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine) 0 0.02122 87 LMOMA output 1 CAETHG_3924 O-ribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose5-phosphate) 0 0.02122 88 LMOMA output 1 CAETHG_1371 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine) 0 0.02122 89 LMOMA output 1 CAETHG_0160 N-ribosylnicotinamide:opτoφocφaτpibosyltransφerase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate) 0 0.02122 90 LMOMA output 2 CAETHG_0248, CAETHG_2721 Reversible transport of L-lactate in symport with protons (H+_nar. + E-lactate_nar. <=> H+ + L-lactate), phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ --> ADP + CO2 + phosphoenolpyruvate) 0 0.020644 91 LMOMA output 2 CAETHG_2107, CAETHG_2721 Potassium absorption (K+_nar. <=> K+), phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ --> ADP + CO2 + phosphoenolpyruvate) 0 0.020584 92 Exit - 1 CAETHG_2721 Phosphoenolpyruvate carboxykinase (PPKK) (ATP + 0 0.02058

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LMOMA oxaloacetate + H+ --> ADP + CO2 + phosphoenolpyruvate) 93 LMOMA output 1 CAETHG_3021 L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline) 0 0.02006 94 BPCY- FBA 4 CAETHG_2751, CAETHG_2753, CAETHG_2909, CAETHG_3293 Citramalate synthase (H2O + pyruvate + acetyl-CoA <=> CoA + citramalate), isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), ATP:pyruvate orthophosphate phosphotransferase (ATP + phosphate + pyruvate + H + -> PPi + AMP + phosphoenolpyruvate), cysteine desulfhydrase (H2O + Lcysteine <=> NH3 + pyruvate + H2S) 0.05233 0.012686 95 BPCY- FBA 3 CAETHG_2753, CAETHG_2909, CAETHG_0498 Isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), ATP: pyruvate- orthophosphate phosphotransferase (ATP + phosphate + pyruvate + H+ -> PPi + AMP + phosphoenolpyruvate), cystathionine beta-lyase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0.02686 0.00855 96 BPCY- FBA 3 CAETHG_2751, CAETHG_2753, CAETHG_2909 Citramalate synthase (H2O + pyruvate + acetyl-CoA <=> CoA + citramalate), isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), ATP:pyruvate orthophosphate phosphotransferase (ATP + phosphate + pyruvate + H + -> PPi + AMP + phosphoenolpyruvate) 0.02545 0.008366 97 BPCY- FBA 2 CAETHG_2753, CAETHG_2909 Isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), ATP: pyruvate- orthophosphate phosphotransferase (ATP + phosphate + pyruvate + H+ -> PPi + AMP + phosphoenolpyruvate) 0.01873 0.007195 98 BPCY- FBA 3 CAETHG_2751, CAETHG_2909, CAETHG_3293 Citramalate synthase (H2O + pyruvate + acetyl-CoA <=> CoA + citramalate), ATP: pyruvate- orthophosphate phosphotransferase (ATP + phosphate + pyruvate + H+ -> PPi + AMP + phosphoenolpyruvate), cysteine desulfhydrase (H2O + L-cysteine <=> NH3 + pyruvate + H2S) 0 0.002528 99 BPCY FBA 3 CAETHG_2751, CAETHG_2909, CAETHG_3611 Citramalate synthase (H2O + pyruvate + acetyl-CoA <=> CoA + citramalate), ATP: pyruvate- orthophosphate phosphotransferase (ATP + phosphate + pyruvate + H+ -> PPi + AMP + phosphoenolpyruvate), threonine dehydratase (L-threonine --> NH3 + 2-oxobutyrate) 0 0.002508 100 BPCY- FBA 2 CAETHG_2751, CAETHG_2909 Citramalate synthase (H2O + pyruvate + acetyl-CoA <=> CoA + citramalate), ATP: pyruvate- orthophosphate phosphotransferase (ATP + phosphate + pyruvate + H+ -> PPi + AMP + phosphoenolpyruvate) 0 0.001842 101 BPCY- FBA 2 CAETHG_2909, CAETHG_3293 ATP: pyruvate orthophosphate phosphotransferase (ATP + phosphate + pyruvate + H+ -> PPi + AMP + phosphoenolpyruvate), cysteine desulfhydrase (H2O + Lcysteine <=> NH3 + pyruvate + H2S) 0 0.001323 102 BPCY- FBA 2 CAETHG_2753, CAETHG_3293 Isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), cysteine desulfhydrase (H2O + L-cysteine <=> NH3 + pyruvate + H2S) 0 0.000573 103 BPCY- FBA 1 CAETHG_2909 ATP: pyruvate orthophosphate phosphotransferase (ATP + phosphate + pyruvate + H+ -> PPi + AMP + phosphoenolpyruvate) 0 0.000573

Example 11.

This example describes perturbations to improve 3-hydroxybutyrate production in Wood-Ljungdahl microorganisms. Metabolic modeling experiments were performed as described in example 1. The production of 3-hydroxybutyrate in Wood-Ljungdahl microorganisms is described, for example, in WO 2017/066498. To model the production of 3-hydroxybutyrate, the following pathway was used in this document: 3-hydroxybutyrate^3-hydroxybutyrate_nar; acetate+acetoacetyl-CoA^acetylCoA+acetoacetate; NADH+H++acetoacetate^NAD+3-hydroxybutyrate; 2.0 acetylCoA^CoA+acetoacetyl-CoA.

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ft Methodology Number of violated Disturbed genes Disturbed reactions Minimum FVA output Compliance score 1 BPCY- FBA 3 CAETHG_2753, CAETHG_29O9, CAETHG_3293 Isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), ATP: pyruvate- orthophosphate phosphotransferase (ATP + phosphate + pyruvate + H+ -> PPi + AMP + phosphoenolpyruvate), cysteine desulfhydrase (H2O + L-cysteine <=> NH3 τη and ru vat + H2S) 0.01233 0.00434 2 BPCY- FBA 3 CAETHG_2753, CAETHG_2909, CAETHG_0498 Isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), ATP: pyruvate- orthophosphate phosphotransferase (ATP + phosphate + pyruvate + H+ -> PPi + AMP + phosphoenolpyruvate), cystathionine betaliase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0 0.002583 3 BPCY- FBA 3 CAETHG_2751, CAETHG_2753, CAETHG_29O9 Citramalate synthase (H2O + pyruvate + acetyl-CoA <=> CoA + citramalate), isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), ATP:pyruvate phosphate phosphotransferase (ATP + phosphate + pyruvate + H+ - > PPi + AMP + phosphoenolpyruvate) 0 0.002477 4 BPCY- FBA 2 CAETHG_2753, CAETHG_29O9 Isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), ATP: pyruvate- orthophosphate phosphotransferase (ATP + phosphate + pyruvate + H+ -> PPi + AMP + phosphoenolpyruvate) 0 0.001788 5 BPCY- FBA 2 CAETHG_2753, CAETHG_29O9 Isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), ATP: pyruvate- orthophosphate phosphotransferase (ATP + phosphate + pyruvate + H+ -> PPi + AMP + phosphoenolpyruvate) 0 0.001475 6 LMOMA output 6 CAETHG_0160, CAETHG_2721, CAETHG_2932, CAETHG_3359, CAETHG_0475, CAETHG_0498 N-ribosylnicotinamide:opτoφocφaτpibosyltransφerase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), phosphoenolpyruvate carboxykinase (RRSC) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0 0.090072 7 LMOMA output 5 CAETHG_0160, CAETHG_2721, N-ribosylnicotinamide:opτoφocφaτpibosyltransferase (phosphate + N-ribosylnicotinamide <=> nicotinamide + 0 0.088912

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CAETHG_2932, CAETHG_3359, CAETHG_0475 ribose-1-phosphate), phosphoenolpyruvate carboxykinase (RRSC) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (B)-acetoin), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 8 LMOMA output 5 CAETHG_0160, CAETHG_2721, CAETHG_2932, CAETHG_3358, CAETHG_0475 N-ribosylnicotinamide:opτoφocφaτpibosyltransφerase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), phosphoenolpyruvate carboxykinase (RRSC) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), alpha-acetolactate decarboxylase (ALCTT --> CO2 + (B)-acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.088912 9 LMOMA output 4 CAETHG_2721, CAETHG_2932, CAETHG_3359, CAETHG_351O Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (R)acetoin), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), 2,6diaminoheptanedioate:2-oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <- 2oxoglutarate + EE-2,6-diaminopimelate) 0 0.08852 10 LMOMA output 4 CAETHG_2721, CAETHG_2932, CAETHG_3359, CAETHG_0474 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (R)acetoin), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), glycine: lipoylprotein oxidoreductase (decarboxylating and acceptor- aminomethylating) (glycine + H+ + lipoylprotein -> CO2 + S-aminomethyldihydrolipoylprotein) 0 0.0884 eleven LMOMA output 4 CAETHG_2721, CAETHG_2932, CAETHG_3359, CAETHG_0475 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (R)acetoin), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0 0.0884 12 LMOMA output 3 CAETHG_3359, CAETHG_351O, CAETHG_0498 ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), 2,6-diaminoheptanedioate: 2oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <- 2-oxoglutarate + LL-2,6diaminopimelate), cystathionine -beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0 0.087852 13 LMOMA output 3 CAETHG_3O21, CAETHG_3359, CAETHG_351O L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), 2,6diaminoheptanedioate: 2-oxoglutarate aminotransferase (H2O + L-glutamate + H + + tetrahydrodipicolinate <- 2oxoglutarate + EE-2,6-diaminopimelate) 0 0.087504 14 LMOMA output 2 CAETHG_3359, CAETHG_351O ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), 2,6-diaminoheptanedioate: 2oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <- 2-oxoglutarate + LL-2,6diaminopimelate) 0 0.087464 15 LMOMA output 2 CAETHG_2721, CAETHG_3359 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.079284 16 LMOMA output 2 CAETHG_2721, CAETHG_3358 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA 0 0.079284

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+ acetyl phosphate) 17 LMOMA output 2 CAETHG_2932, CAETHG_3358 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (R)acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.073692 18 LMOMA output 2 CAETHG_3358, CAETHG_0686 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), L-threonine acetaldehyde lyase (L-threonine - -> glycine + acetaldehyde) 0 0.057428 19 LMOMA output 2 CAETHG_3358, CAETHG_0498 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0 0.054844 20 LMOMA output 2 CAETHG_1371, CAETHG_3358 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate) 0 0.054664 21 LMOMA output 2 CAETHG_3358, CAETHG_3924 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate), D-ribose-!,5-phosphomutase (ribose-1phosphate <=> ribose-5-phosphate) 0 0.054664 22 LMOMA output 2 CAETHG_0160, CAETHG_3359 N-ribosylnicotinamide: orthophosphate ribosyltransferase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0 0.054664 23 LMOMA output 2 CAETHG_0160, CAETHG_3358 N-ribosylnicotinamide: orthophosphate ribosyltransferase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.054664 24 LMOMA output 2 CAETHG_1270, CAETHG_3358 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.05458 25 LMOMA output 2 CAETHG_2475, CAETHG_3358 dGTP triphosphohydrolase (H2O + dGTP -> H+ + deoxyguanosine + triphosphate), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate) 0 0.053004 26 LMOMA output 2 CAETHG_2799, CAETHG_3358 NADP-dependent electron bifurcation [FeFe]dehydrogenase (Hyt) (NADP + oxidized ferredoxin + 2.0 H2 <=> NADPH + 3.0 H+ + reduced ferredoxin), phosphate transacetylase (phosphate + acetylCoA + H+ <=> CoA + acetyl phosphate) 0 0.052724 27 LMOMA output 2 CAETHG_2789, CAETHG_3358 Formate hydrogen lyase (also known as hydrogen-dependent CO2 reductase) (CO2 + H2 --> formate + H+), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.052724 28 LMOMA output 2 CAETHG_2795, CAETHG_3358 NADP-dependent electron bifurcation [FeFe]dehydrogenase (Hyt) (NADP + oxidized ferredoxin + 2.0 H2 <=> NADPH + 3.0 H+ + reduced ferredoxin), phosphate transacetylase (phosphate + acetylCoA + H+ <=> CoA + acetyl phosphate) 0 0.052724 29 LMOMA output 2 CAETHG_2794, CAETHG_3358 NADP-dependent electron bifurcation [FeFe]dehydrogenase (Hyt) (NADP + oxidized ferredoxin + 2.0 H2 <=> NADPH + 3.0 H+ + reduced ferredoxin), phosphate transacetylase (phosphate + acetylCoA + H+ <=> CoA + acetyl phosphate) 0 0.052724 thirty LMOMA output 2 CAETHG_2796, CAETHG_3358 NADP-dependent electron bifurcation [FeFe]dehydrogenase (Hyt) (NADP + oxidized ferredoxin + 2.0 H2 <=> NADPH + 3.0 H+ + reduced ferredoxin), phosphate transacetylase (phosphate + acetylCoA + H+ <=> CoA + acetyl phosphate) 0 0.052724 31 Exit - 2 CAETHG_2791, Formate hydrogen lyase (also known as hydrogen- 0 0.052724

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LMOMA CAETHG_3358 dependent CO2 reductase) (CO2 + H2 --> formate + H+), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate) 32 LMOMA output 2 CAETHG_279O, CAETHG_3358 Formate hydrogen lyase (also known as hydrogen-dependent CO2 reductase) (CO2 + H2 --> formate + H+), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.052724 33 LMOMA output 2 CAETHG_2798, CAETHG_3358 NADP-dependent electron bifurcation [FeFe]dehydrogenase (Hyt) (NADP + oxidized ferredoxin + 2.0 H2 <=> NADPH + 3.0 H+ + reduced ferredoxin), phosphate transacetylase (phosphate + acetylCoA + H+ <=> CoA + acetyl phosphate) 0 0.052724 34 LMOMA output 2 CAETHG_2793, CAETHG_3358 Formate hydrogen lyase (also known as hydrogen-dependent CO2 reductase) (CO2 + H2 --> formate + H+), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.052724 35 LMOMA output 2 CAETHG_3293, CAETHG_3358 Cysteine desulfhydrase (H2O + L-cysteine <=> NH3 + pyruvate + H2S), phosphate transacetylase (phosphate + acetylCoA + H+ <=> CoA + acetylphosphate) 0 0.052712 36 LMOMA output 2 CAETHG_3O21, CAETHG_3358 L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.052652 37 LMOMA output 2 0, CAETHG_3358 Acetyl-CoAzharbondioxide ligase (ADP-forming) (ATP + acetyl-CoA + H2CO3 -> ADP + phosphate + H+ + malonyl-CoA), phosphate transacetylase (phosphate + acetylCoA + H+ <=> CoA + acetylphosphate) 0 0.052616 38 LMOMA output 2 CAETHG_0233, CAETHG_3358 4-imidazolone-5-propanoate amidohydrolase (H2O + 4-imidazolone-5-propanoate -> N-formimino-E-glutamate), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.052616 39 LMOMA output 2 CAETHG_0234, CAETHG_3358 4,5-dihydro-4-oxo-5-imidazolepropanoate hydrolyase (4imidazolone-5-propanoate <=> H2O + urocanate), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate) 0 0.052616 40 LMOMA output 2 CAETHG_0234, CAETHG_3359 4,5-dihydro-4-oxo-5-imidazolepropanoate hydrolyase (4imidazolone-5-propanoate <=> H2O + urocanate), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0 0.052616 41 LMOMA output 2 CAETHG_3164, CAETHG_3358 UMP: pyrophosphate phosphoribosyltransferase (uracil + PRPP -> PPi + UMP), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.052584 42 LMOMA output 2 CAETHG_2107, CAETHG_3358 Potassium absorption (K+_nar <=> K+), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.05258 43 LMOMA output 1 CAETHG_3359 ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.052576 44 LMOMA output 1 CAETHG_3358 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.052576 45 LMOMA output 2 CAETHG_2721, CAETHG_2751 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), citramalate synthase (H2O + pyruvate + acetyl-CoA <=> CoA + citramalate) 0 0.02074 46 LMOMA output 2 CAETHG_2721, CAETHG_0498 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0 0.0207

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47 LMOMA output 2 CAETHG_127O, CAETHG_2721 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), phosphoenolpyruvate carboxykinase (PPKK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate) 0 0.020628 48 LMOMA output 2 CAETHG_2721, CAETHG_3924 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), Dribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose-5phosphate) 0 0.020628 49 LMOMA output 2 CAETHG_1224, CAETHG_2721 L-serine ammonia lyase (L-serine -> NH3 + pyruvate), phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ --> ADP + CO2 + phosphoenolpyruvate) 0 0.02054 50 LMOMA output 2 CAETHG_1225, CAETHG_2721 L-serine ammonia lyase (L-serine -> NH3 + pyruvate), phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ --> ADP + CO2 + phosphoenolpyruvate) 0 0.02054 51 LMOMA output 2 CAETHG_21O7, CAETHG_2721 Potassium absorption (K+_nar. <=> K+), phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ --> ADP + CO2 + phosphoenolpyruvate) 0 0.020448 52 LMOMA output 1 CAETHG_2721 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ --> ADP + CO2 + phosphoenolpyruvate) 0 0.020444 53 LMOMA output 1 CAETHG_127O AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine) 0 0.020432 54 LMOMA output 1 CAETHG_0160 N-ribosylnicotinamide:orthophosphate ribosyltransferase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate) 0 0.020432 55 LMOMA output 1 CAETHG_1371 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine) 0 0.020432 56 LMOMA output 1 CAETHG_3924 O-ribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose-5phosphate) 0 0.020432 57 LMOMA output 2 CAETHG_0234, CAETHG_3O21 4,5-dihydro-4-oxo-5-imidazolepropanoate hydrolyase (4imidazolone-5-propanoate <=> H2O + urocanate), L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline) 0 0.020032

Example 12.

This example describes disturbances to improve methyl ethyl ketone (MEK) production, i.e. 2butanone, in Wood-Ljungdahl microorganisms. Metabolic modeling experiments were performed as described in example 1. MEK production in Wood-Ljungdahl microorganisms is described, for example, in WO 2012/024522 and WO 2013/185123. To model methyl ethyl ketone production, the following pathway was used in this paper: NADH+H++(K)-acetoin—>NAD+meso-2,3-butanediol; meso-2,3-butanediol -> H ₂ O + MEK; N++MEK—>N+nar .+MEK_nar.

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ft Methodology Oh co ABOUT Disturbed genes Disturbed reactions Minimum FVA output Compliance score 1 LMOMA output 5 0, CAETHG_0160, CAETHG_3359, CAETHG_3510, CAETHG_O498 Acetyl-CoAzharbondioxide ligase (ADP-forming) (ATP + acetyl-CoA + H2CO3 -> ADP + phosphate + H+ + malonylCoA), N- ribosylnicotinamide durtophosphate ribosyltransferase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), 2,6diaminoheptanedioate: 2-oxoglutarate aminotransferase (H2O + L-glut amat + H+ + tetrahydrodipicolinate <- 2oxoglutarate + EE-2,6-diaminopimelate), cystathionine betaliase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0.04120 0.028524 2 LMOMA output 5 0, CAETHG_1371, CAETHG_3359, CAETHG_3510, CAETHG_O498 Acetyl-CoAzharbondioxide ligase (ADP-forming) (ATP + acetyl-CoA + H2CO3 -> ADP + phosphate + H+ + malonylCoA), adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine) , ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), 2,6diaminoheptanedioate:2-oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <- 2oxoglutarate + EE-2,6-diaminopimelate), cystathionine -betaliase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0.04120 0.028524 3 LMOMA output 5 0, CAETHG_3359, CAETHG_3510, CAETHG_3924, CAETHG_O498 Acetyl-CoAzharbondioxide ligase (ADP-forming) (ATP + acetyl-CoA + H2CO3 -> ADP + phosphate + H+ + malonylCoA), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), 2.6 -diaminoheptanedioate:2oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6- diaminopimelate), O-ribose-1,5-phosphomutase (ribose-1phosphate <=> ribose-5-phosphate), cystathionine beta-lyase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0.04120 0.028524 4 LMOMA output 5 0, CAETHG_1270, CAETHG_3359, CAETHG_3510, CAETHG_0498 Acetyl-CoAzharbondioxide ligase (ADP-forming) (ATP + acetyl-CoA + H2CO3 -> ADP + phosphate + H+ + malonylCoA), AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), 2,6diaminoheptanedioate:2-oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <- 2oxoglutarate + EE-2,6-diaminopimelate), cystathionine betaliase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0.04120 0.028524 5 LMOMA output 5 0, CAETHG_0160, CAETHG_3359, CAETHG_3510, CAETHG_0498 Acetyl-CoAzharbondioxide ligase (ADP-forming) (ATP + acetyl-CoA + H2CO3 -> ADP + phosphate + H+ + malonylCoA), N- ribosylnicotinamide durtophosphate ribosyltransferase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), 2,6diaminoheptanedioate: 2-oxoglutarate aminotransferase (H2O + L-glut amat + H+ + tetrahydrodipicolinate <- 2oxoglutarate + EE-2,6-diaminopimelate), cystathionine betaliase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0.04120 0.028508 6 LMOMA output 5 0, CAETHG_0160, CAETHG_3021, CAETHG_3359, CAETHG_3510 Acetyl-CoAzharbondioxide ligase (ADP-forming) (ATP + acetyl-CoA + H2CO3 -> ADP + phosphate + H+ + malonylCoA), N- ribosylnicotinamide durtophosphate ribosyltransferase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), L-arginine iminohydrolase (H2O + Larginine <=> NH3 + citrulline), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), 2,6-diaminoheptanedioate: 2oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6diaminopimelate) 0.04120 0.028476

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7 LMOMA output 5 CAETHG_0160, CAETHG_2751, CAETHG_3359, CAETHG_351O, CAETHG_0498 N-ribosylnicotinamide: opτoφocφaτpibosylτpansφerase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), citramalate synthase (H2O + pyruvate + acetyl-CoA <=> CoA + citramalate), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), 2,6-diaminoheptanedioate: 2oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6- diaminopimelate), cystathionine beta-lyase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0.04287 0.028464 8 LMOMA output 4 0, CAETHG_0160, CAETHG_3359, CAETHG_3510 Acetyl-CoAzharbondioxide ligase (ADP-forming) (ATP + acetyl-CoA + H2CO3 -> ADP + phosphate + H+ + malonylCoA), N- ribosylnicotinamide: orthophosphate ribosyltransferase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), 2,6diaminoheptanedioate: 2-oxoglutarate aminotransferase (H2O + L- glutamate + H+ + tetrahydrodipicolinate <- 2oxoglutarate + u_-2,6-diaminopimelate) 0.04120 0.02844 9 LMOMA output 4 0, CAETHG_3359, CAETHG_3510, CAETHG_3924 Acetyl-CoAzharbondioxide ligase (ADP-forming) (ATP + acetyl-CoA + H2CO3 -> ADP + phosphate + H+ + malonylCoA), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), 2.6 -diaminoheptanedioate:2oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6diaminopimelate), O-ribose-1,5-phosphomutase (ribose-1phosphate <=> ribose-5-phosphate ) 0.04120 0.02844 10 LMOMA output 4 0, CAETHG_1270, CAETHG_3359, CAETHG_3510 Acetyl-CoAzharbondioxide ligase (ADP-forming) (ATP + acetyl-CoA + H2CO3 -> ADP + phosphate + H+ + malonylCoA), AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), 2,6diaminoheptanedioate:2-oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <- 2oxoglutarate + i.-2,6-diaminopimelate) 0.04120 0.02844 eleven LMOMA output 4 CAETHG_3021, CAETHG_3359, CAETHG_3510, CAETHG_0498 L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), 2,6diaminoheptanedioate: 2-oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <— 2oxoglutarate + EE-2,6-diaminopimelate), cystathionine betaliase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0.04120 0.028296 12 LMOMA output 3 CAETHG_3359, CAETHG_3510, CAETHG_0498 ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), 2,6-diaminoheptanedioate: 2oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6- diaminopimelate), cystathionine beta-lyase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0.04120 0.02828 13 LMOMA output 3 CAETHG_3021, CAETHG_3359, CAETHG_3510 L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), 2,6diaminoheptanedioate: 2-oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <- 2oxoglutarate + u_-2,6-diaminopimelate) 0.04120 0.028256 14 LMOMA output 3 CAETHG_3359, CAETHG_3510, CAETHG_0498 ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), 2,6-diaminoheptanedioate: 2oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6- diaminopimelate), cystathionine beta-lyase (H2O + 0.04120 0.028252

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cystathionine -> NH3 + pyruvate + homocysteine) 15 LMOMA output 3 CAETHG_3293, CAETHG_3359, CAETHG_351O Cysteine desulfhydrase (H2O + L-cysteine <=> NH3 + pyruvate + H2S), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), 2,6-diaminoheptanedioate: 2oxoglutarate aminotransferase (H2O + L-glutamate + H + + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6- diaminopimelate) 0.04120 0.028248 16 LMOMA output 2 CAETHG_3359, CAETHG_351O ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), 2,6-diaminoheptanedioate: 2oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6- diaminopimelate) 0.04120 0.02824 17 LMOMA output 2 CAETHG_3358, CAETHG_351O Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), 2,6-diaminoheptanedioate:2- oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6- diaminopimelate) 0 0.02824 18 LMOMA output 3 CAETHG_3021, CAETHG_3359, CAETHG_351O L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), 2,6diaminoheptanedioate: 2-oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <- 2oxoglutarate + u_-2,6-diaminopimelate) 0 0.028224 19 LMOMA output 2 CAETHG_3359, CAETHG_351O ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), 2,6-diaminoheptanedioate: 2oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6- diaminopimelate) 0 0.028216 20 LMOMA output 3 CAETHG_0160, CAETHG_3359, CAETHG_0498 N-ribosylnicotinamide: orthophosphate ribosyltransferase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), cystathionine betaliase (H2O + cystathionine -- > NH3 + pyruvate + homocysteine) 0 0.02774 21 LMOMA output 3 CAETHG_3359, CAETHG_3924, CAETHG_0498 ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), O-ribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose-5-phosphate), cystathionine betaliase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0 0.02774 22 LMOMA output 3 CAETHG_127O, CAETHG_3359, CAETHG_0498 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), cystathionine betaliase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0 0.02774 23 LMOMA output 3 CAETHG_1371, CAETHG_3359, CAETHG_0498 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0 0.02774 24 LMOMA output 2 CAETHG_3359, CAETHG_0498 ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), cystathionine beta-lyase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0 0.027712 25 LMOMA output 3 CAETHG_3021, CAETHG_3359, CAETHG_3924 L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), C-ribose-1,5phosphomutase (ribose-1-phosphate <=> ribose 5-phosphate) 0 0.027688 26 LMOMA output 2 CAETHG_127O, CAETHG_3359 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.027676

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27 LMOMA output 2 CAETHG_0160, CAETHG_3359 N-ribosylnicotinamide: orthophosphate ribosyltransferase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.027676 28 LMOMA output 2 CAETHG_1371, CAETHG_3359 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0 0.027676 29 LMOMA output 2 CAETHG_3359, CAETHG_3924 ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), O-ribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose-5-phosphate) 0 0.027676 thirty LMOMA output 2 CAETHG_1270, CAETHG_3358 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), phosphate transacetylase (phosphate + acetylCoA + H+ <=> CoA + acetylphosphate) 0 0.027676 31 LMOMA output 2 CAETHG_3021, CAETHG_3359 L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.027656 32 LMOMA output 1 CAETHG_3359 ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.027644 33 LMOMA output 1 CAETHG_3358 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.027644

Example 13.

This example describes disturbances to improve acetolactate production in Wood-Ljungdahl microorganisms. Metabolic modeling experiments were performed as described in Example 1. Acetolactate is a native product of at least some WoodLjungdahl microorganisms.

ft Methodology Oh co ABOUT Disturbed genes Disturbed reactions Minimum FVA output Compliance score 1 LMOMA output 5 CAETHG_2751, CAETHG_2932, CAETHG_3359, CAETHG_3510, CAETHG_0498 Citramalate synthase (H2O + pyruvate + acetyl-CoA <=> CoA + citramalate), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), 2,6diaminoheptanedioate:2-oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + EE-2,6-diaminopimelate), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0.079303 0.19563 2 LMOMA output 5 CAETHG_1371, CAETHG_2932, CAETHG_3359, CAETHG_3510, CAETHG_0498 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), 2,6diaminoheptanedioate:2-oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + EE-2,6-diaminopimelate), cystathionine beta-lyase (H2O + cystathionine -- > NH3 + pyruvate + homocysteine) 0.077232 0.195495 3 LMOMA output 5 CAETHG_0160, CAETHG_2932, CAETHG_3359, N-ribosylnicotinamide:opτoφocφaτpibosyltransφerase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), alpha-acetolactate decarboxylase (ALCTT - 0.077232 0.195495

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CAETHG_351O, CAETHG_0498 -> CO2 + (K)-acetoin), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), 2,6diaminoheptanedioate: 2-oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2- oxoglutarate + EE-2,6-diaminopimelate), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 4 LMOMA output 5 CAETHG_2932, CAETHG_3359, CAETHG_351O, CAETHG_3924, CAETHG_0498 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (R)acetoin), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), 2,6diaminoheptanedioate:2-oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + EE-2,6-diaminopimelate), O-ribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose-5-phosphate), cystathionine betaliase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0.077232 0.195495 5 LMOMA output 5 CAETHG_1270, CAETHG_2932, CAETHG_3359, CAETHG_351O, CAETHG_0498 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), 2, 6diaminoheptanedioate:2-oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + EE-2,6-diaminopimelate), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0.077232 0.195495 6 LMOMA output 4 CAETHG_2721, CAETHG_2753, CAETHG_3358, CAETHG_0686 Phosphoenolpyruvate carboxykinase (PPKK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate) , Lthreonine acetaldehyde lyase (L-threonine -> glycine + acetaldehyde) 0 0.16721 7 LMOMA output 4 CAETHG_2753, CAETHG_3293, CAETHG_3358, CAETHG_0686 Isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), cysteine desulfhydrase (H2O + Lcysteine <=> NH3 + pyruvate + H2S), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate), Lthreonine acetaldehyde lyase (L-threonine -> glycine + acetaldehyde) 0 0.16456 8 LMOMA output 4 CAETHG_3358, CAETHG_351O, CAETHG_3924, CAETHG_0498 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), 2,6-diaminoheptanedioate:2- oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6- diaminopimelate), D-ribose-!,5-phosphomutase (ribose-1phosphate <=> ribose-5-phosphate), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0 0.16301 9 LMOMA output 3 CAETHG_3358, CAETHG_351O, CAETHG_0498 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), 2,6-diaminoheptanedioate:2- oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6diaminopimelate), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0 0.162785 10 LMOMA output 3 CAETHG_3358, CAETHG_351O, CAETHG_3924 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), 2,6-diaminoheptanedioate:2- oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6- diaminopimelate), O-ribose-1,5-phosphomutase (ribose-1phosphate <=> ribose-5-phosphate) 0 0.16169 eleven LMOMA output 3 CAETHG_1371, CAETHG_3358, CAETHG_351O Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), 2,6diaminoheptanedioate:2-oxoglutarate aminotransferase (H2O + L -glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate 0 0.16169

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+ EE-2,6-diaminopimelate) 12 LMOMA output 3 CAETHG_0160, CAETHG_3358, CAETHG_351O N-ribosylnicotinamide: orthophosphate ribosyltransferase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), phosphate transacetylase (phosphate + acetylCoA + H+ <=> CoA + acetylphosphate), 2,6diaminoheptanedioate:2-oxoglutarate aminotransferase (H2O + L -glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + EE-2,6-diaminopimelate) 0 0.16169 13 LMOMA output 3 CAETHG_2932, CAETHG_3358, CAETHG_351O Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (R)acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), 2,6-diaminoheptanedioate:2oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6- diaminopimelate) 0.077231 0.15909 14 LMOMA output 3 CAETHG_3293, CAETHG_3358, CAETHG_3510 Cysteine desulfhydrase (H2O + L-cysteine <=> NH3 + pyruvate + H2S), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), 2,6-diaminoheptanedioate:2oxoglutarate aminotransferase (H2O + L-glutamate + H + + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6- diaminopimelate) 0 0.15344 15 LMOMA output 3 CAETHG_3358, CAETHG_351O, CAETHG_O9O9 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), 2,6-diaminoheptanedioate:2- oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6- diaminopimelate), prephenate: NAD+-oxidoreductase (decarboxylating) (NAD + prephenate --> NADH + CO2 + phydroxyphenylpyruvate) 0 0.150755 16 LMOMA output 3 CAETHG_3021, CAETHG_3358, CAETHG_351O L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), 2,6-diaminoheptanedioate:2oxoglutarate aminotransferase (H2O + L-glutamate + H + + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6- diaminopimelate) 0 0.15038 17 LMOMA output 2 CAETHG_3359, CAETHG_351O ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), 2,6-diaminoheptanedioate: 2- oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6- diaminopimelate) 0 0.150325 18 LMOMA output 2 CAETHG_3358, CAETHG_351O Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), 2,6-diaminoheptanedioate:2- oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6- diaminopimelate) 0 0.150325 19 LMOMA output 4 CAETHG_0160, CAETHG_2753, CAETHG_3358, CAETHG_0686 N-ribosylnicotinamide:opτoφocφaτpibosyltransferase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate), L-threonine acetaldehyde lyase (L-threonine -> glycine + acetaldehyde) 0 0.13579 20 LMOMA output 3 CAETHG_2753, CAETHG_3358, CAETHG_0686 Isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), L-threonine acetaldehyde lyase (L-threonine -> glycine + acetaldehyde) 0 0.1302 21 LMOMA output 3 CAETHG_2721, CAETHG_3358, CAETHG_0686 Phosphoenolpyruvate carboxykinase (PPKK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + 0 0.127735

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acetyl phosphate), L-threonine acetaldehyde lyase (L-threonine -> glycine + acetaldehyde) 22 LMOMA output 2 CAETHG_2721, CAETHG_3358 Phosphoenolpyruvate carboxykinase (PPKK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate) 0 0.12009 23 LMOMA output 3 CAETHG_1371, CAETHG_3358, CAETHG_0686 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), L-threonine acetaldehyde lyase (L-threonine -> glycine + acetaldehyde) 0 0.110555 24 LMOMA output 3 CAETHG_0160, CAETHG_3358, CAETHG_0686 N-ribosylnicotinamide:opτoφocφaτpibosyltransφerase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), phosphate transacetylase (phosphate + acetylCoA + H+ <=> CoA + acetylphosphate), L-threonine acetaldehyde lyase (L-tre onine -> glycine + acetaldehyde) 0 0.110555 25 LMOMA output 3 CAETHG_3358, CAETHG_0498, CAETHG_0686 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate), cystathionine beta-lyase (H2O + cystathionine -> NH3 + pyruvate + homocysteine), L- Threonine acetaldehyde lyase (L-threonine -> glycine + acetaldehyde) 0 0.10917 26 LMOMA output 3 CAETHG_3O21, CAETHG_3358, CAETHG_0686 L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), L-threonine acetaldehyde lyase (Lthreonine -> glycine + acetaldehyde) 0 0.10734 27 LMOMA output 3 CAETHG_3164, CAETHG_3358, CAETHG_0686 UMP: pyrophosphate phosphoribosyltransferase (uracil + PRPP -> PPi + UMP), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), L-threonine acetaldehyde lyase (Lthreonine -> glycine + acetaldehyde) 0 0.10725 28 LMOMA output 2 CAETHG_3358, CAETHG_0686 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate), L-threonine acetaldehyde lyase (L-threonine -> glycine + acetaldehyde) 0 0.10722 29 LMOMA output 2 CAETHG_3359, CAETHG_0686 ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), L-threonine acetaldehyde lyase (Lthreonine -> glycine + acetaldehyde) 0 0.10722 thirty LMOMA output 3 CAETHG_3358, CAETHG_3924, CAETHG_0498 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate), O-ribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose-5-phosphate), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0 0.104905 31 LMOMA output 3 CAETHG_127O, CAETHG_3358, CAETHG_0498 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine ) 0 0.104905 32 LMOMA output 3 CAETHG_0160, CAETHG_3358, CAETHG_0498 N-ribosylnicotinamide: opτoφocφaτpibosyltransφerase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), phosphate transacetylase (phosphate + acetylCoA + H+ <=> CoA + acetylphosphate), cystathionine beta-lyase (H2 O + cystathionine -- > NH3 + pyruvate + homocysteine) 0 0.104905 33 LMOMA output 3 CAETHG_3299, CAETHG_3358, CAETHG_0498 2-deoxy-O-ribose-5-phosphate acetaldehyde lyase (deoxyribose-5-phosphate <=> acetaldehyde + glyceraldehyde-3-phosphate), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), cystathionine betaliase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0 0.10331 34 LMOMA output 3 CAETHG_3O21, CAETHG_3358, CAETHG_0498 L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), cystathionine beta-lyase (H2O + 0 0.10228

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cystathionine --> NH3 + pyruvate + homocysteine) 35 LMOMA output 3 CAETHG_3164, CAETHG_3358, CAETHG_0498 UMP: pyrophosphate phosphoribosyltransferase (uracil + PRPP -> PPi + UMP), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0 0.10218 36 LMOMA output 2 CAETHG_3358, CAETHG_0498 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), cystathionine beta-lyase (H2O + cystathionine - -> NH3 + pyruvate + homocysteine) 0 0.102155 37 LMOMA output 2 CAETHG_1371, CAETHG_3358 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate) 0 0.10147 38 LMOMA output 2 CAETHG_1270, CAETHG_3358 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.10147 39 LMOMA output 2 CAETHG_3358, CAETHG_3924 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), O-ribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose 5-phosphate) 0 0.10147 40 LMOMA output 2 CAETHG_0160, CAETHG_3358 N-ribosylnicotinamide: opτoφocφaτpibosyltransφerase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), phosphate transacetylase (phosphate + acetylCoA + H+ <=> CoA + acetylphosphate) 0 0.10147 41 LMOMA output 2 CAETHG_3299, CAETHG_3358 2-deoxy-O-ribose-5-phosphate acetaldehyde lyase (deoxyribose-5-phosphate <=> acetaldehyde + glyceraldehyde-3-phosphate), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.09974 42 LMOMA output 2 CAETHG_2475, CAETHG_3358 dGTP triphosphohydrolase (H2O + dGTP -> H+ + deoxyguanosine + triphosphate), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate) 0 0.099725 43 LMOMA output 2 CAETHG_3021, CAETHG_3358 L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.0988 44 LMOMA output 2 CAETHG_3164, CAETHG_3358 UMP: pyrophosphate phosphoribosyltransferase (uracil + PRPP -> PPi + UMP), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.098685 45 LMOMA output 2 CAETHG_2107, CAETHG_3358 Potassium absorption (K+_nar <=> K+), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.098675 46 LMOMA output 1 CAETHG_3358 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.09867 47 LMOMA output 1 CAETHG_3359 ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.09867 48 LMOMA output 2 CAETHG_2932, CAETHG_3924 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (R)acetoin), O-ribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose-5-phosphate) 0 0.048115 49 LMOMA output 1 CAETHG_2932 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (R)acetoin) 0 0.04552 50 LMOMA output 2 CAETHG_2721, CAETHG_0909 Phosphoenolpyruvate carboxykinase (PPKK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), prephenate: NAD+ oxidoreductase (decarboxylating) (NAD + prephenate -> NADH + CO2 + p-hydroxyphenylpyruvate) 0 0.021365 51 LMOMA output 2 CAETHG_0248, CAETHG_2721 Reversible transport of L-lactate in symport with protons (H+_nar. + E-lactate_nar. <=> H+ + L-lactate), phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ --> ADP + CO2 + phosphoenolpyruvate) 0 0.021235

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52 LMOMA output 2 CAETHG_1270, CAETHG_2721 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), phosphoenolpyruvate carboxykinase (PPKK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate) 0 0.02115 53 LMOMA output 2 CAETHG_0160, CAETHG_2721 N-ribosylnicotinamide: opτoφocφaτpibosylτpancφerase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoeno lpyruvate) 0 0.02115 54 LMOMA output 2 CAETHG_2721, CAETHG_3924 Phosphoenolpyruvate carboxykinase (PPKK) (ATP + oxaloacetate + H+ --> ADP + CO2 + phosphoenolpyruvate), Dribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose-5phosphate) 0 0.02115 55 LMOMA output 2 CAETHG_2721, CAETHG_2751 Phosphoenolpyruvate carboxykinase (PPKK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), citramalate synthase (H2O + pyruvate + acetyl-CoA <=> CoA + citramalate) 0 0.021085 56 LMOMA output 1 CAETHG_0160 N-ribosylnicotinamide:opτoφocφaτpibosyltransφerase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate) 0 0.020825 57 LMOMA output 1 CAETHG_1270 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine) 0 0.020825 58 LMOMA output 1 CAETHG_1371 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine) 0 0.020825 59 LMOMA output 1 CAETHG_3924 O-ribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose-5phosphate) 0 0.020825 60 LMOMA output 2 CAETHG_2721, CAETHG_3021 Phosphoenolpyruvate carboxykinase (PPKK) (ATP + oxaloacetate + H+ --> ADP + CO2 + phosphoenolpyruvate), L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline) 0 0.02046 61 LMOMA output 2 CAETHG_2107, CAETHG_2721 Potassium absorption (K+_nar. <=> K+), phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ --> ADP + CO2 + phosphoenolpyruvate) 0 0.020425 62 LMOMA output 1 CAETHG_2721 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ --> ADP + CO2 + phosphoenolpyruvate) 0 0.02042 63 LMOMA output 1 CAETHG_2751 Citramalate synthase (H2O + pyruvate + acetyl-CoA <=> CoA + citramalate) 0 0.020095 64 LMOMA output 1 CAETHG_3021 L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline) 0 0.020045

Example 14.

This example describes disturbances to improve isoprene production in Wood-Ljungdahl microorganisms. Metabolic modeling experiments were performed as described in Example 1. Isoprene production in Wood-Ljungdahl microorganisms is described, for example, in WO 2013/180584. To model isoprene production, the following pathway was used herein: 2.0 acetylCoA—>CoA+acetoacetyl-CoA; 2.0 NADH+2.0 H++(8)-3-hydroxy-3-methylglutaryl-CoA—>2.0

NAD+CoA+(K)-mevalonate; ATP+(L)-mevalonate—>ADP+(K)-5-phosphomevalonate;ATP+(K)-5-phosphomevalonate—>ADP+K)-5-diphosphomevalonate;ATP+(K)-5-diphosphomevalonate—>ADP+phosphate+CO ₂ +isopentenyl diphosphate; isopentenyl diphosphate—>DMAPP;DMAPP—>PP1+isoprene; H ₂ O+acetylCoA+acetoacetyl-CoA—>CoA+(8)-3-hydroxy-3-methylglutaryl-CoA;isoprene—>isoprennar. These disruptions can also be used to improve IPP/DMAPP production and/or downstream products from IPP/DMAPP, such as farnesene and other terpenoids.

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ft Methodology Oh co ABOUT Disturbed genes Disturbed reactions Minimum FVA output Compliance score 1 LMOMA output 5 CAETHG_2O62, CAETHG_2479, CAETHG_2721, CAETHG_2932, CAETHG_3358 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate ) 0 0.05024 2 LMOMA output 5 CAETHG_0160, CAETHG_2721, CAETHG_2932, CAETHG_3358, CAETHG_O498 N-ribosylnicotinamide: opτoφocφaτpibosylτpancφerase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoeno lpyruvate), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), cystathionine beta-lyase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0 0.049965 3 LMOMA output 5 CAETHG_0160, CAETHG_2721, CAETHG_2932, CAETHG_3O21, CAETHG_3358 N-ribosylnicotinamide: opτoφocφaτpibosylτpancφerase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoeno lpyruvate), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.04994 4 LMOMA output 5 CAETHG_2721, CAETHG_2932, CAETHG_3O21, CAETHG_3358, CAETHG_3924 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), transacetyl phosphate for (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate), O-ribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose-5-phosphate) 0 0.04994 5 LMOMA output 4 CAETHG_2721, CAETHG_2932, CAETHG_3358, CAETHG_3924 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate ), O-ribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose-5-phosphate) 0 0.04993 6 LMOMA output 4 CAETHG_0160, CAETHG_2721, CAETHG_2932, CAETHG_3358 N-ribosylnicotinamide: opτoφocφaτpibosylτpancφerase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoeno lpyruvate), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.04993

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7 LMOMA output 4 CAETHG_0160, CAETHG_2721, CAETHG_2932, CAETHG_3359 N-ribosylnicotinamide: opτoφocφaτpibosylτpancφerase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoeno lpyruvate), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0 0.04993 8 LMOMA output 4 CAETHG_1270, CAETHG_2721, CAETHG_2932, CAETHG_3358 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.04991 9 LMOMA output 3 CAETHG_2721, CAETHG_2932, CAETHG_3358 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ --> ADP + CO2 + phosphoenolpyruvate), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.049595 10 LMOMA output 4 CAETHG_2932, CAETHG_3358, CAETHG_3510, CAETHG_3924 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), 2,6-diaminoheptanedioate:2- oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <- 2-oxoglutarate + LL-2,6diaminopimelate), O-ribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose-5-phosphate) 0 0.04102 eleven LMOMA output 4 CAETHG_1270, CAETHG_2932, CAETHG_3358, CAETHG_3510 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), alpha-acetolactate decarboxylase (ALCTT --> CO2 + (R)acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), 2 ,6-diaminoheptanedioate:2- oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <- 2-oxoglutarate + LL-2,6- diaminopimelate) 0 0.04102 12 LMOMA output 4 CAETHG_2932, CAETHG_3O21, CAETHG_3358, CAETHG_3510 Alpha-acetolactate decarboxylase (ALCTT --> CO2 + (K)-acetoin), L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate), 2,6-diaminoheptanedioate:2- oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <- 2-oxoglutarate + LL-2,6diaminopimelate) 0 0.04041 13 LMOMA output 3 CAETHG_2932, CAETHG_3359, CAETHG_3510 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (Rj-acetoin), ATP: acetate phosphotransferase (ATP + H + + propionate --> ADP + propionyl phosphate), 2,6-diaminoheptanedioate: 2- oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <- 2-oxoglutarate + LL-2,6diaminopimelate) 0 0.040385 14 LMOMA output 3 CAETHG_2932, CAETHG_3358, CAETHG_3510 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), 2,6-diaminoheptanedioate:2- oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <— 2-oxoglutarate + LL-2,6diaminopimelate) 0 0.040385 15 LMOMA output 3 CAETHG_1270, CAETHG_2932, CAETHG_3358 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), alpha-acetolactate decarboxylase (ALCTT --> CO2 + (R)acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate) 0 0.035525 16 LMOMA output 3 CAETHG_0160, CAETHG_2932, CAETHG_3358 N-ribosylnicotinamide:opτoφocφaτpibosyltransφerase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), phosphate transacetylase (phosphate + ace til-CoA + H+ < => KoA + 0 0.035525

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acetyl phosphate) 17 LMOMA output 3 CAETHG_2932, CAETHG_3358, CAETHG_3924 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), O-ribose-1,5-phosphomutase (ribose-1-phosphate < => ribose 5-phosphate) 0 0.035525 18 LMOMA output 3 CAETHG_2475, CAETHG_2932, CAETHG_3358 dGTP triphosphohydrolase (H2O + dGTP -> H+ + deoxyguanosine + triphosphate), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate) 0 0.03288 19 LMOMA output 3 0, CAETHG_2932, CAETHG_3358 Acetyl-CoAzharbondioxide ligase (ADP-forming) (ATP + acetyl-CoA + H2CO3 -> ADP + phosphate + H+ + malonyl-CoA), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.03003 20 LMOMA output 3 CAETHG_2932, CAETHG_3358, CAETHG_0498 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), cystathionine beta-lyase (H2O + cystathionine -> NH3 + pyruvate + homocysteine ) 0 0.029935 21 LMOMA output 3 CAETHG_0234, CAETHG_2932, CAETHG_3358 4,5-dihydro-4-oxo-5-imidazolepropanoate hydrolyase (4- imidazolone-5-propanoate <=> H2O + urocanate), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.029835 22 LMOMA output 3 CAETHG_0233, CAETHG_2932, CAETHG_3358 4-imidazolone-5-propanoate amidohydrolase (H2O + 4-imidazolone 5-propanoate --> N-formimino-E-glutamate), alpha acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.029835 23 LMOMA output 3 CAETHG_2932, CAETHG_3164, CAETHG_3358 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), UMP: pyrophosphate phosphoribosyltransferase (uracil + PRPP --> PPi + UMP), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate) 0 0.02962 24 LMOMA output 3 CAETHG_2932, CAETHG_3358, CAETHG_0909 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), prephenate:NAD+ oxidoreductase (decarboxylating) (NAD + prephenate -> NADH + CO2 + phydroxyphenylpyruvate) 0 0.02948 25 LMOMA output 2 CAETHG_2932, CAETHG_3359 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (Rj-acetoin), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0 0.029455 26 LMOMA output 2 CAETHG_2932, CAETHG_3358 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.029455 27 LMOMA output 2 CAETHG_3358, CAETHG_3510 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), 2,6-diaminoheptanedioate:2- oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <- 2-oxoglutarate + LL-2,6diaminopimelate) 0 0.028035 28 LMOMA output 2 CAETHG_3358, CAETHG_0498 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate), cystathionine beta-lyase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0 0.027595 29 LMOMA output 2 CAETHG_3021, CAETHG_3358 L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.027555 thirty LMOMA output 1 CAETHG_3358 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.02754

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31 LMOMA output 1 CAETHG_3359 ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.02754 32 LMOMA output 2 CAETHG_O1O2, CAETHG_0092 0 0.021305 33 LMOMA output 2 CAETHG_0160, CAETHG_2721 N-ribosylnicotinamide: opτoφocφaτpibosylτpancφerase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoeno lpyruvate) 0 0.02015 34 LMOMA output 2 CAETHG_0160, CAETHG_3O21 N-ribosylnicotinamide: opτoφocφaτpibosyltransferase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate), L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline) 0 0.020115 35 LMOMA output 1 CAETHG_0160 N-ribosylnicotinamide:opτoφocφaτpibosyltransφerase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate) 0 0.02011 36 LMOMA output 1 CAETHG_1371 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine) 0 0.02011 37 LMOMA output 1 CAETHG_127O AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine) 0 0.02011 38 LMOMA output 1 CAETHG_3924 O-ribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose-5- phosphate) 0 0.02011 39 LMOMA output 1 CAETHG_O498 Cystathionine beta-lyase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0 0.020055 40 LMOMA output 1 CAETHG_2721 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate) 0 0.020055 41 LMOMA output 1 CAETHG_2751 Citramalate synthase (H2O + pyruvate + acetyl-CoA <=> CoA + citramalate) 0 0.02003 42 LMOMA output 1 CAETHG_3021 L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline) 0 0.020005

Example 15.

This example describes disturbances to improve adipic acid production in Wood-Ljungdahl microorganisms. Metabolic modeling experiments were performed as described in Example 1. Adipic acid production in Wood-Ljungdahl microorganisms is described, for example, in WO 2017/0066498. To model the production of adipic acid, the following pathway was used: ATP + CoA + succinate—ADP + phosphate + succinyl-CoA; NAD + CoA + 2-oxoglutarate—NADH + CO ₂ + succinyl-CoA; acetyl-CoA + succinyl-CoA— CoA + 3 -oxoadipyl-CoA; NADH+H++3 -oxoadipyl-CoA—NAD+3-hydroxyadipyl-CoA; 3-hydroxyadipyl-CoA-—2,3-dehydroadipyl-CoA; NADH+H++2,3dehydroadipyl-CoA—NAD+adipyl-CoA; phosphate+adipyl-CoA—CoA+adipyl-P; ADP+adipylR-ATP+adipate; adipat-adipatnar.

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ft Methodology Number of violated Disturbed genes Disturbed reactions Minimum FVA output Compliance score 1 BPCY FBA 1 CAETHG_2024 Glutamine synthetase (GOGAT) (ATP + NH3 + L-glutamate --> ADP + phosphate + L-glutamine + H+) 0.02858 0.003813 2 LMOMA output 3 CAETHG_2024, CAETHG_2O62, CAETHG_2479 Glutamine synthetase (GOGAT) (ATP + NH3 + L-glutamate -> ADP + phosphate + L-glutamine + H+) 0.09198 0.057966 3 LMOMA output 5 CAETHG_2024, CAETHG_2799, CAETHG_29O9, CAETHG_2932, CAETHG_O9O9 Glutamine synthetase (GOGAT) (ATP + NH3 + L-glutamate -> ADP + phosphate + L-glutamine + H+), NADP-dependent electron bifurcation [FeFeJ-dehydrogenase (Hyt) (NADP + oxidized ferredoxin + 2.0 H2 < => NADPH + 3.0 H+ + reduced ferredoxin), ATP: pyruvatorthophosphate phosphotransferase (ATP + phosphate + pyruvate + H+ -> PPi + AMP + phosphoenolpyruvate), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (Rj-acetoin), prephenate: NAD+-oxidoreductase (decarboxylating) (NAD + prephenate --> NADH + CO2 + phydroxyphenylpyruvate) 0.02786 0.028758 4 LMOMA output 4 CAETHG_2024, CAETHG_2796, CAETHG_29O9, CAETHG_2932 Glutamine synthetase (GOGAT) (ATP + NH3 + L-glutamate -> ADP + phosphate + L-glutamine + H+), NADP-dependent electron bifurcation [FeFeJ-dehydrogenase (Hyt) (NADP + oxidized ferredoxin + 2.0 H2 < => NADPH + 3.0 H+ + reduced ferredoxin), ATP: pyruvatorthophosphate phosphotransferase (ATP + phosphate + pyruvate + H+ -> PPi + AMP + phosphoenolpyruvate), alpha-acetolactate decarboxylase (ALCTT --> CO2 + (P)-acetoin) 0.02787 0.028566 5 LMOMA output 4 CAETHG_2024, CAETHG_2795, CAETHG_29O9, CAETHG_2932 Glutamine synthetase (GOGAT) (ATP + NH3 + L-glutamate -> ADP + phosphate + L-glutamine + H+), NADP-dependent electron bifurcation [FeFeJ-dehydrogenase (Hyt) (NADP + oxidized ferredoxin + 2.0 H2 < => NADPH + 3.0 H+ + reduced ferredoxin), ATP: pyruvatorthophosphate phosphotransferase (ATP + phosphate + pyruvate + H+ -> PPi + AMP + phosphoenolpyruvate), alpha-acetolactate decarboxylase (ALCTT --> CO2 + (P)-acetoin) 0.02787 0.028566 6 LMOMA output 3 CAETHG_2024, CAETHG_29O9, CAETHG_2932 Glutamine synthetase (GOGAT) (ATP + NH3 + L-glutamate -> ADP + phosphate + L-glutamine + H+), ATP:pyruvatorophosphate phosphotransferase (ATP + phosphate + pyruvate + H+ -> PPi + AMP + phosphoenolpyruvate), alpha-acetolactate decarboxylase (ALCTT --> CO2 + (P)-acetoin) 0.02787 0.028464 7 LMOMA output 3 CAETHG_2024, CAETHG_2794, CAETHG_2932 Glutamine synthetase (GOGAT) (ATP + NH3 + L-glutamate -> ADP + phosphate + L-glutamine + H+), NADP-dependent electron bifurcation [FeFeJ-dehydrogenase (Hyt) (NADP + oxidized ferredoxin + 2.0 H2 < => NADPH + 3.0 H+ + reduced ferredoxin), alpha-acetolactate decarboxylase (ALCTT --> CO2 + (P)-acetoin) 0.02858 0.028086 8 LMOMA output 3 CAETHG_2024, CAETHG_2795, CAETHG_2932 Glutamine synthetase (GOGAT) (ATP + NH3 + L-glutamate -> ADP + phosphate + L-glutamine + H+), NADP-dependent electron bifurcation [FeFeJ-dehydrogenase (Hyt) (NADP + oxidized ferredoxin + 2.0 H2 < => NADPH + 3.0 H+ + reduced ferredoxin), alpha-acetolactate decarboxylase (ALCTT --> CO2 + (P)-acetoin) 0.02858 0.028086 9 LMOMA output 3 CAETHG_2024, CAETHG_2799, CAETHG_2932 Glutamine synthetase (GOGAT) (ATP + NH3 + L-glutamate -> ADP + phosphate + L-glutamine + H+), NADP-dependent electron-bifurcation [FeFeJ-dehydrogenase (Hyt) 0.02858 0.028086

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10 LMOMA output 3 CAETHG_2024, CAETHG_2796, CAETHG_2932 (NADP + oxidized ferredoxin + 2.0 H2 <=> NADPH + 3.0 H+ + reduced ferredoxin), alpha-acetolactate decarboxylase (ALCTT --> CO2 + (P)-acetoin) Glutamine synthetase (GOGAT) (ATP + NH3 + L-glutamate -> ADP + phosphate + L-glutamine + H+), NADP-dependent electron bifurcation [FeFeJ-dehydrogenase (Hyt) (NADP + oxidized ferredoxin + 2.0 H2 < => NADPH + 3.0 H+ + reduced ferredoxin), alpha-acetolactate decarboxylase (ALCTT --> CO2 + (P)-acetoin) 0.02858 0.028086 eleven LMOMA output 3 CAETHG_2024, CAETHG_2798, CAETHG_2932 Glutamine synthetase (GOGAT) (ATP + NH3 + L-glutamate -> ADP + phosphate + L-glutamine + H+), NADP-dependent electron bifurcation [FeFeJ-dehydrogenase (Hyt) (NADP + oxidized ferredoxin + 2.0 H2 < => NADPH + 3.0 H+ + reduced ferredoxin), alpha-acetolactate decarboxylase (ALCTT --> CO2 + (H)-acetoin) 0.02858 0.028086 12 LMOMA output 3 CAETHG_2024, CAETHG_2797, CAETHG_2932 Glutamine synthetase (GOGAT) (ATP + NH3 + L-glutamate -> ADP + phosphate + L-glutamine + H+), NADP-dependent electron bifurcation [FeFeJ-dehydrogenase (Hyt) (NADP + oxidized ferredoxin + 2.0 H2 < => NADPH + 3.0 H+ + reduced ferredoxin), alpha-acetolactate decarboxylase (ALCTT --> CO2 + (P)-acetoin) 0.02858 0.028086 13 LMOMA output 3 CAETHG_2024, CAETHG_2932, CAETHG_3021 Glutamine synthetase (GOGAT) (ATP + NH3 + L-glutamate -> ADP + phosphate + L-glutamine + H+), alpha acetolactate decarboxylase (ALCTT --> CO2 + (B)-acetoin), L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline) 0.02854 0.028074 14 LMOMA output 3 0, CAETHG_2024, CAETHG_2932 Acetyl-CoAzharbondioxide ligase (ADP-forming) (ATP + acetyl-CoA + H2CO3 --> ADP + phosphate + H+ + malonyl-CoA), glutamine synthetase (GOGAT) (ATP + NH3 + Lglutamate -> ADP + phosphate + L -glutamine + H+), alpha-acetolactate decarboxylase (ALCTT --> CO2 + (P)-acetoin) 0.02858 0.028032 15 LMOMA output 2 CAETHG_2024, CAETHG_2932 Glutamine synthetase (GOGAT) (ATP + NH3 + L-glutamate -> ADP + phosphate + L-glutamine + H+), alpha acetolactate decarboxylase (ALCTT --> CO2 + (P)-acetoin) 0.02858 0.028002 16 LMOMA output 2 CAETHG_2024, CAETHG_2475 Glutamine synthetase (GOGAT) (ATP + NH3 + L-glutamate -> ADP + phosphate + L-glutamine + H+), dGTP- triphosphohydrolase (H2O + dGTP --> H+ + deoxyguanosine + triphosphate) 0.02858 0.027156 17 LMOMA output 2 CAETHG_2024, CAETHG_3299 Glutamine synthetase (GOGAT) (ATP + NH3 + L-glutamate -> ADP + phosphate + L-glutamine + H+), 2-deoxy-O-ribose-5-phosphate acetaldehyde lyase (deoxyribose-5-phosphate <=> acetaldehyde + glyceraldehyde-3- phosphate) 0.02858 0.027156 18 LMOMA output 1 CAETHG_2024 Glutamine synthetase (GOGAT) (ATP + NH3 + L-glutamate --> ADP + phosphate + L-glutamine + H+) 0.02858 0.02715 19 LMOMA output 2 CAETHG_2024, CAETHG_3510 Glutamine synthetase (GOGAT) (ATP + NH3 + L-glutamate -> ADP + phosphate + L-glutamine + H+), 2,6- diaminoheptanedioate:2-oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <— 2oxoglutarate + u_-2,6-diaminopimelate) 0.02858 0.027126 20 LMOMA output 2 CAETHG_1371, CAETHG_3021 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine), L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline) 0 0.020616 21 LMOMA output 1 CAETHG_1371 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine) 0 0.020592 22 LMOMA output 1 CAETHG_3924 O-ribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose5-phosphate) 0 0.020592 23 LMOMA output 1 CAETHG_0160 N-ribosylnicotinamide:opτoφocφaτpibosyltransφerase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1-phosphate) 0 0.020592 24 LMOMA output 1 CAETHG_1270 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine) 0 0.020592 25 LMOMA output 1 CAETHG_3021 L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline) 0 0.020034

Example 16.

This example describes disturbances to improve 2-aminobenzoate production in Wood-Ljungdahl microorganisms. Metabolic modeling experiments were performed as described in example 1. Production of 2-aminobenzoate in Wood-Ljungdahl microorganisms is described, for example, in WO

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2016/191625. To model the production of 2-aminobenzoate in this document, the following path was used: NH ₃ + chorismate^ H ₂ O + pyruvate + H ++ 2-aminobenzoate._________________________

ft Methodology Oh co ABOUT Disturbed genes Disturbed reactions Minimum FVA output Compliance score 1 LMOMA output 5 0, CAETHG_3021, CAETHG_3359, CAETHG_3510, CAETHG_3924 Acetyl-CoAzharbondioxide ligase (ADP-forming) (ATP + acetyl-CoA + H2CO3 -> ADP + phosphate + H+ + malonyl-CoA), L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), 2,6diaminoheptanedioate:2-oxoglutarate aminotransferase (H2O + Lglutamate + H+ + tetrahydrodipicolinate <- 2-oxoglutarate + LL2,6-diaminopimelate), O-ribose-1, 5-phosphomutase (ribose-1phosphate <=> ribose-5-phosphate) 0 0.025375 2 LMOMA output 4 0, CAETHG_3359, CAETHG_3510, CAETHG_3924 Acetyl-CoAzharbondioxide ligase (ADP-forming) (ATP + acetyl-CoA + H2CO3 -> ADP + phosphate + H+ + malonyl-CoA), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), 2 ,6-diaminoheptanedioate:2- oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6- diaminopimelate), O-ribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose-5-phosphate) 0 0.025368 3 LMOMA output 4 0, CAETHG_127O, CAETHG_3359, CAETHG_3510 Acetyl-CoAzharbondioxide ligase (ADP-forming) (ATP + acetyl-CoA + H2CO3 -> ADP + phosphate + H+ + malonyl-CoA), AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), 2,6diaminoheptanedioate:2-oxoglutarate aminotransferase (H2O + Lglutamate + H+ + tetrahydrodipicolinate <- 2-oxoglutarate + LL2,6-diaminopimelate) 0 0.025368 4 LMOMA output 4 CAETHG_2753, CAETHG_3359, CAETHG_3510, CAETHG_0686 Isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), 2,6diaminoheptanedioate: 2-oxoglutarate aminotransferase (H2O + Lglutamate + H+ + tetrahydrodipicolinate <- 2-oxoglutarate + LL- 0 0.025361

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2,6-diaminopimelate), L-threonine acetaldehyde lyase (L-threonine - -> glycine + acetaldehyde) 5 LMOMA output 5 O, CAETHG_2932, CAETHG_3359, CAETHG_3510, CAETHG_0498 Acetyl-CoAzharbondioxide ligase (ADP-forming) (ATP + acetyl-CoA + H2CO3 -> ADP + phosphate + H+ + malonyl-CoA), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (P)-acetoin), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), 2,6-diaminoheptanedioate: 2- oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6- diaminopimelate), cystathionine beta-lyase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0 0.025305 6 LMOMA output 5 CAETHG_2932, CAETHG_3359, CAETHG_3510, CAETHG_3924, CAETHG_0498 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), 2,6-diaminoheptanedioate: 2- oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6diaminopimelate), O-ribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose-5-phosphate) , cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0 0.025277 7 LMOMA output 3 0, CAETHG_3359, CAETHG_3510 Acetyl-CoAzharbondioxide ligase (ADP-forming) (ATP + acetyl-CoA + H2CO3 -> ADP + phosphate + H+ + malonyl-CoA), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), 2 ,6-diaminoheptanedioate:2- oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6- diaminopimelate) 0 0.025256 8 LMOMA output 4 CAETHG_0160, CAETHG_2753, CAETHG_3358, CAETHG_351O N-ribosylnicotinamide:opτoφocφaτpibosyltransferase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1phosphate), isocitrate dehydrogenase (NAD + isocitrate <=> NADH + CO2 + 2-oxoglutarate + H+), phosphate transacetylase (phosphate + acetyl-CoA + H + <=> CoA + acetyl phosphate), 2,6diaminoheptanedioate:2-oxoglutarate aminotransferase (H2O + Lglutamate + H+ + tetrahydrodipicolinate <- 2-oxoglutarate + LL2,6-diaminopimelate) 0 0.025235 9 LMOMA output 3 CAETHG_3359, CAETHG_3510, CAETHG_3924 ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), 2,6-diaminoheptanedioate: 2- oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6- diaminopimelate), O-ribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose-5-phosphate) 0 0.025221 10 LMOMA output 3 CAETHG_1270, CAETHG_3359, CAETHG_3510 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), 2,6diaminoheptanedioate: 2-oxoglutarate aminotransferase (H2O + Lglutamate + H+ + tetrahydrodipicolinate < - 2-oxoglutarate + LL2,6-diaminopimelate) 0 0.025221 eleven LMOMA output 3 CAETHG_0160, CAETHG_3358, CAETHG_3510 N-ribosylnicotinamide: opτoφocφaτpibosyltransferase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1phosphate), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), 2,6-diaminoheptanedioate: 2- oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6- diaminopimelate) 0 0.025221 12 LMOMA output 3 CAETHG_0160, CAETHG_3359, CAETHG_3510 N-ribosylnicotinamide: opτoφocφaτpibosyltransferase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1phosphate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), 2,6-diaminohept andioate:2oxoglutarate aminotransferase (H2O + L- glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6- 0 0.025221

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diaminopimelate) 13 LMOMA output 4 CAETHG_3021, CAETHG_3293, CAETHG_3359, CAETHG_3510 L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), cysteine desulfhydrase (H2O + L-cysteine <=> NH3 + pyruvate + H2S), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate ), 2,6diaminoheptanedioate:2-oxoglutarate aminotransferase (H2O + Lglutamate + H+ + tetrahydrodipicolinate <- 2-oxoglutarate + LL2,6-diaminopimelate) 0 0.025088 14 LMOMA output 3 CAETHG_3293, CAETHG_3359, CAETHG_3510 Cysteine desulfhydrase (H2O + L-cysteine <=> NH3 + pyruvate + H2S), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), 2,6-diaminoheptanedioate: 2oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6- diaminopimelate) 0 0.025081 15 LMOMA output 3 CAETHG_3021, CAETHG_3359, CAETHG_3510 L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate), 2,6diaminoheptanedioate: 2-oxoglutarate aminotransferase (H2O + Lglutamate + H+ + tetrahydrodipicolinate <- 2-oxoglutarate + LL2,6-diaminopimelate) 0 0.025081 16 LMOMA output 2 CAETHG_3359, CAETHG_3510 ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), 2,6-diaminoheptanedioate: 2- oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6- diaminopimelate) 0 0.025074 17 LMOMA output 2 CAETHG_3358, CAETHG_3510 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate), 2,6-diaminoheptanedioate:2- oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6diaminopimelate) 0 0.025074 18 LMOMA output 2 CAETHG_3359, CAETHG_3510 ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), 2,6-diaminoheptanedioate: 2- oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6- diaminopimelate) 0 0.025067 19 LMOMA output 3 CAETHG_3021, CAETHG_3359, CAETHG_O498 L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), cystathionine betaliase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0 0.024752 20 LMOMA output 2 CAETHG_3359, CAETHG_O498 ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), cystathionine beta-lyase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0 0.024745 21 LMOMA output 2 CAETHG_3358, CAETHG_O498 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate), cystathionine beta-lyase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0 0.024738 22 LMOMA output 2 CAETHG_3021, CAETHG_3359 L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0 0.024724 23 LMOMA output 1 CAETHG_3358 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.024717 24 LMOMA output 1 CAETHG_3359 ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0 0.024717 25 LMOMA output 1 CAETHG_3293 Cysteine desulfhydrase (H2O + L-cysteine <=> NH3 + pyruvate + H2S) 0 0.020384 26 LMOMA output 2 CAETHG_O498, CAETHG_0686 Cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine), L-threonine acetaldehyde lyase (L-threonine --> 0 0.020307

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glycine + acetaldehyde) 27 LMOMA output 2 CAETHG_2751, CAETHG_0498 Citramalate synthase (H2O + pyruvate + acetyl-CoA <=> CoA + citramalate), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0 0.020167 28 LMOMA output 2 CAETHG_3021, CAETHG_0498 L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0 0.020132 29 LMOMA output 1 CAETHG_0498 Cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0 0.020125 thirty LMOMA output 2 CAETHG_2751, CAETHG_3021 Citramalate synthase (H2O + pyruvate + acetyl-CoA <=> CoA + citramalate), L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline) 0 0.020076 31 LMOMA output 1 CAETHG_2751 Citramalate synthase (H2O + pyruvate + acetyl-CoA <=> CoA + citramalate) 0 0.020069 32 LMOMA output 1 CAETHG_0160 N-ribosylnicotinamide:opτoφocφaτpibosyltransφerase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1phosphate) 0 0.020013 33 LMOMA output 1 CAETHG_1371 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine) 0 0.020013 34 LMOMA output 1 CAETHG_1270 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine) 0 0.020013 35 LMOMA output 1 CAETHG_3924 O-ribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose-5phosphate) 0 0.020013 36 LMOMA output 1 CAETHG_0686 L-threonine acetaldehyde lyase (L-threonine -> glycine + acetaldehyde) 0 0.020006

Example 17.

This example describes perturbations to improve salicylate production in Wood-Ljungdahl microorganisms. Metabolic modeling experiments were performed as described in example 1. Salicylate production in Wood-Ljungdahl microorganisms is described, for example, in WO 2016/191625. The following pathway was used to model salicylate production in this paper: chorismate^isochorismate; isochorismate^salicylate+pyruvate,__________________________________________

ft Methodology Oh co ABOUT Disturbed genes Disturbed reactions Minimum FVA output Compliance score 1 LMOMA output 3 0, CAETHG_3164, CAETHG_0686 Acetyl-CoAzharbondioxide ligase (ADP-forming) (ATP + acetyl-CoA + H2CO3 -> ADP + phosphate + H+ + malonyl-CoA), UMP: pyrophosphate phosphoribosyltransferase (uracil + PRPP -> PPi + UMP), L-threonine acetaldehyde lyase ( L-threonine -> glycine + acetaldehyde) 0 0.020174 2 LMOMA output 3 CAETHG_3021, CAETHG_3299, CAETHG_0686 L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), 2-deoxy-O-ribose-5-phosphate acetaldehyde lyase (deoxyribose-5-phosphate <=> acetaldehyde + glyceraldehyde-3phosphate), L-threonine acetaldehyde lyase (L- threonine --> glycine + acetaldehyde) 0 0.020174 3 LMOMA output 1 CAETHG_0686 L-threonine acetaldehyde lyase (L-threonine -> glycine + acetaldehyde) 0 0.020167

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Example 18.

This example describes perturbations to improve chorismate production in Wood-Ljungdahl microorganisms. Metabolic modeling experiments were performed as described in example 1. The production of chorismate in Wood-Ljungdahl microorganisms is described, for example, in WO 2016/191625. Chorismate is a native product of at least some WoodLjungdahl microorganisms. These same disturbances would be expected to also increase the flux through dehydroshikimate, a metabolic node located immediately upstream of chorismate.

ft Methodology Oh co ABOUT Disturbed genes Disturbed reactions Minimum FVA output Compliance score 1 LMOMA output 4 CAETHG_127O, CAETHG_21O7, CAETHG_3O21, CAETHG_0498 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), potassium uptake (K+_nar <=> K+), L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), cystathionine beta-lyase ( Н2О + cystathionine --> NH3 + pyruvate + homocysteine) 0 0.02128 2 LMOMA output 4 CAETHG_0160, CAETHG_3O21, CAETHG_351O, CAETHG_0498 N-ribosylnicotinamide: opτoφocφaτpibosyltransφerase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1phosphate), L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), 2,6-diaminoheptanedio. at:2- oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6- diaminopimelate), cystathionine beta-lyase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0 0.02128 3 Exit - 4 CAETHG_0160, N-ribosylnicotinamide:optoφocφaτpibosyltransferase 0 0.02128

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LMOMA CAETHG_21O7, CAETHG_3021, CAETHG_0498 (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1phosphate), potassium absorption (K+_nar. <=> K+), L- arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 4 LMOMA output 4 CAETHG_3021, CAETHG_351O, CAETHG_3924, CAETHG_0498 L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), 2,6-diaminoheptanedioate:2- oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6diaminopimelate), D-ribose-!,5-phosphomutase (ribose-1-phosphate <=> ribose-5-phosphate) , cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0 0.02128 5 LMOMA output 3 CAETHG_127O, CAETHG_3021, CAETHG_0498 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), cystathionine beta-lyase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0 0.02127 6 LMOMA output 3 CAETHG_0160, CAETHG_3021, CAETHG_0498 N-ribosylnicotinamide:opτoφocφaτpibosyltransφerase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1phosphate), L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), cystathionine beta-lyase ( H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0 0.02127 7 LMOMA output 3 CAETHG_1371, CAETHG_3021, CAETHG_0498 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine), L-arginine iminohydrolase (H2O + Larginine <=> NH3 + citrulline), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0 0.02127 8 LMOMA output 3 CAETHG_3021, CAETHG_3924, CAETHG_0498 L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), O-ribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose-5-phosphate), cystathionine beta-lyase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0 0.02127 9 LMOMA output 3 CAETHG_0160, CAETHG_21O7, CAETHG_0498 N-ribosylnicotinamide: opτoφocφaτpibosyltransferase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1phosphate), potassium uptake (K+_nar <=> K+), cystathionine betaliase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0 0.0211 10 LMOMA output 3 CAETHG_127O, CAETHG_351O, CAETHG_0498 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), 2,6-diaminoheptanedioate: 2- oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6- diaminopimelate), cystathionine beta-lyase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0 0.0211 eleven LMOMA output 3 CAETHG_127O, CAETHG_21O7, CAETHG_0498 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), potassium uptake (K+_nar <=> K+), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0 0.0211 12 LMOMA output 2 CAETHG_3924, CAETHG_0498 O-ribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose-5phosphate), cystathionine beta-lyase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0 0.02109 13 LMOMA output 2 CAETHG_127O, CAETHG_0498 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0 0.02109 14 LMOMA output 2 CAETHG_1371, CAETHG_0498 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0 0.02109 15 LMOMA output 2 CAETHG_0160, CAETHG_0498 N-ribosylnicotinamide:optoφocφaτpibosyltransferase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1phosphate), cystathionine beta-lyase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0 0.02109

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16 LMOMA output 2 CAETHG_3021, CAETHG_3924 L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), O-ribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose-5-phosphate) 0 0.02065 17 LMOMA output 2 CAETHG_0248, CAETHG_3924 Reversible transport of L-lactate in symport with protons (H+_nar. + E-lactate_nar. <=> H+ + L-lactate), O-ribose-1,5phosphomutase (ribose-1-phosphate<=> ribose-5- phosphate) 0 0.02064 18 LMOMA output 1 CAETHG_1371 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine) 0 0.02062 19 LMOMA output 1 CAETHG_3924 O-ribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose-5phosphate) 0 0.02062 20 LMOMA output 1 CAETHG_0160 N-ribosylnicotinamide:opτoφocφaτpibosyltransφerase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1phosphate) 0 0.02062 21 LMOMA output 1 CAETHG_127O AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine) 0 0.02062 22 LMOMA output 1 CAETHG_3O21 L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline) 0 0.02003

Example 19.

This example describes disturbances to improve farnesene production in WoodLjungdahl microorganisms. Metabolic modeling experiments were performed as described in example 1. Farnesene production in Wood-Ljungdahl microorganisms is described, for example, in WO 2013/180584. To model farnesene production, the following pathway was used herein: 2.0 acetylCoA–CoA+acetoacetyl-CoA; H2O+acetyl-CoA+acetoacetyl-CoA—CoA+(S)-3 -hydroxy-3 methylglutaryl-CoA; 2.0 NADH+2.0 H++(S)-3-hydroxy-3-methylglutaryl-CoA--2.0 NAD+CoA+(I)mevalonate; ATP+(R)-mevalonate—ADP+(R)-5-phospho mevalonate; ATP+(R)-5diphosphomevalonate—ADP+phosphate+CO2+isopentenyl diphosphate; ATP+(R)-5diphosphomevalonate—ADP+phosphate+CO2+isopentenyl diphosphate; isopentenyl diphosphate—DMAPP; 2,0 isopentenyl diphosphate+DMAPP-PPi+trans,trans-farnesyl diphosphate; trans,transfarnesyl diphosphate—farnesene+PPi; farnesene—farnesennar._____________________ _______

ft Methodology Oh co ABOUT Disturbed genes Disturbed reactions Minimum FVA output Compliance score 1 LMOMA output 5 CAETHG_2062, CAETHG_2479, CAETHG_3293, CAETHG_3359, CAETHG_3510 Cysteine desulfhydrase (H2O + L-cysteine <=> NH3 + pyruvate + H2S), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), 2,6-diaminoheptanedioate: 2oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6- diaminopimelate) 0 0.023775

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2 LMOMA output 5 CAETHG_2O62, CAETHG_2479, CAETHG_3359, CAETHG_351O, CAETHG_0686 ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), 2,6-diaminoheptanedioate: 2- oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6- diaminopimelate), L-threonine acetaldehyde lyase (L-threonine -> glycine + acetaldehyde) 0 0.02376 3 LMOMA output 6 CAETHG_2O62, CAETHG_2479, CAETHG_2751, CAETHG_29O9, CAETHG_3359, CAETHG_351O Citramalate synthase (H2O + pyruvate + acetyl-CoA <=> CoA + citramalate), ATP: pyruvate-orthophosphate phosphotransferase (ATP + phosphate + pyruvate + H+ --> PPi + AMP + phosphoenolpyruvate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), 2,6-diaminoheptanedioate:2- oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6- diaminopimelate) 0 0.02376 4 LMOMA output 5 CAETHG_2O62, CAETHG_2479, CAETHG_2932, CAETHG_3359, CAETHG_351O Alpha-acetolactate decarboxylase (ALCTT-> CO2 + (K)-acetoin), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), 2,6-diaminoheptanedioate: 2- oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6- diaminopimelate) 0 0.02376 5 LMOMA output 4 CAETHG_2O62, CAETHG_2479, CAETHG_3359, CAETHG_351O ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), 2,6-diaminoheptanedioate: 2- oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6- diaminopimelate) 0 0.023745 6 LMOMA output 4 CAETHG_2O62, CAETHG_2479, CAETHG_3359, CAETHG_351O ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), 2,6-diaminoheptanedioate: 2- oxoglutarate aminotransferase (H2O + L-glutamate + H+ + tetrahydrodipicolinate <-- 2-oxoglutarate + LL-2,6- diaminopimelate) 0 0.02373 Ί LMOMA output 5 CAETHG_2O62, CAETHG_2479, CAETHG_2932, CAETHG_3359, CAETHG_0686 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), L-threonine acetaldehyde lyase (L-threonine -> glycine + acetaldehyde) 0 0.02364 8 LMOMA output 4 0, CAETHG_1270, CAETHG_3359, CAETHG_0498 Acetyl-CoAzharbondioxide ligase (ADP-forming) (ATP + acetyl-CoA + H2CO3 -> ADP + phosphate + H+ + malonyl-CoA), AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), cystathionine betaliase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0 0.0234 9 LMOMA output 3 0, CAETHG_127O, CAETHG_3359 Acetyl-CoAzharbondioxide ligase (ADP-forming) (ATP + acetyl-CoA + H2CO3 -> ADP + phosphate + H+ + malonyl-CoA), AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0 0.023385 10 LMOMA output 3 0, CAETHG_3359, CAETHG_0498 Acetyl-CoAzharbondioxide ligase (ADP-forming) (ATP + acetyl-CoA + H2CO3 -> ADP + phosphate + H+ + malonyl-CoA), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), cystathionine -beta-lyase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0 0.023325 eleven LMOMA output 3 CAETHG_127O, CAETHG_3359, CAETHG_0498 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), cystathionine betaliase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0 0.02331 12 LMOMA output 2 CAETHG_1371, CAETHG_3358 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetylphosphate) 0 0.023295

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13 LMOMA output 2 CAETHG_1371, CAETHG_3359 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.023295 14 LMOMA output 2 CAETHG_127O, CAETHG_3359 AMP: pyrophosphate phosphory6osyltransferase (PPi + AMP <=> PRPP + adenine), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0 0.023295 15 LMOMA output 2 CAETHG_0160, CAETHG_3359 N-ribosylnicotinamide:optoφocφaτpibosyltransferase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1phosphate), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.023295 16 LMOMA output 2 CAETHG_3359, CAETHG_3924 ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), O-ribose-1,5-phosphomutase (ribose-1phosphate <=> ribose-5-phosphate) 0 0.023295 17 LMOMA output 2 CAETHG_127O, CAETHG_3358 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.023295 18 LMOMA output 2 CAETHG_3359, CAETHG_0498 ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), cystathionine beta-lyase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0 0.02268 19 LMOMA output 2 CAETHG_3358, CAETHG_0498 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate), cystathionine beta-lyase (H2O + cystathionine -> NH3 + pyruvate + homocysteine) 0 0.02268 20 LMOMA output 2 0, CAETHG_3359 Acetyl-CoAzharbondioxide ligase (ADP-forming) (ATP + acetyl-CoA + H2CO3 -> ADP + phosphate + H+ + malonyl-CoA), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.022665 21 LMOMA output 2 CAETHG_3359, CAETHG_O9O9 ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), prephenate: NAD+ oxidoreductase (decarboxylating) (NAD + prephenate --> NADH + CO2 + phydroxyphenylpyruvate) 0 0.022665 22 LMOMA output 2 CAETHG_3359, CAETHG_0686 ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate), L-threonine acetaldehyde lyase (L-threonine --> glycine + acetaldehyde) 0 0.022605 23 LMOMA output 2 CAETHG_2932, CAETHG_3359 Alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin), ATP: acetate phosphotransferase (ATP + H+ + propionate -> ADP + propionyl phosphate) 0 0.02235 24 LMOMA output 2 CAETHG_3O21, CAETHG_3359 L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline), ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0 0.022305 25 LMOMA output 1 CAETHG_3358 Phosphate transacetylase (phosphate + acetyl-CoA + H+ <=> CoA + acetyl phosphate) 0 0.021945 26 LMOMA output 1 CAETHG_3359 ATP: acetate phosphotransferase (ATP + H+ + propionate --> ADP + propionyl phosphate) 0 0.021945 27 LMOMA output 2 CAETHG_127O, CAETHG_0686 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine), L-threonine acetaldehyde lyase (L-threonine -> glycine + acetaldehyde) 0 0.020235 28 LMOMA output 2 CAETHG_3293, CAETHG_0686 Cysteine desulfhydrase (H2O + L-cysteine <=> NH3 + pyruvate + H2S), L-threonine acetaldehyde lyase (L-threonine -> glycine + acetaldehyde) 0 0.020205 29 LMOMA output 2 CAETHG_1371, CAETHG_2721 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine), phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate) 0 0.02016 thirty Exit - 2 CAETHG_1371, Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> 0 0.020145

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LMOMA CAETHG_0498 phosphate + H+ + adenosine), cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 31 LMOMA output 2 CAETHG_2475, CAETHG_0686 dGTP triphosphohydrolase (H2O + dGTP --> H+ + deoxyguanosine + triphosphate), L-threonine acetaldehyde lyase (L-threonine -> glycine + acetaldehyde) 0 0.02013 32 LMOMA output 2 CAETHG_1371, CAETHG_2751 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine), citramalate synthase (H2O + pyruvate + acetyl-CoA <=> CoA + citramalate) 0 0.020115 33 LMOMA output 2 0, CAETHG_1371 Acetyl-CoAzharbondioxide ligase (ADP-forming) (ATP + acetyl-CoA + H2CO3 -> ADP + phosphate + H+ + malonyl-CoA), adenosine-5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine) 0 0.0201 34 LMOMA output 2 CAETHG_1371, CAETHG_3021 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine), L-arginine iminohydrolase (H2O + Larginine <=> NH3 + citrulline) 0 0.0201 35 LMOMA output 2 CAETHG_1371, CAETHG_0248 Adenosine-5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine), reversible transport of L-lactate in symport with protons (H+_nar. + E-lactate_nar. <=> H+ + Llactate) 0 0.0201 36 LMOMA output 1 CAETHG_0686 L-threonine acetaldehyde lyase (L-threonine -> glycine + acetaldehyde) 0 0.0201 37 LMOMA output 1 CAETHG_1270 AMP: pyrophosphate phosphoribosyltransferase (PPi + AMP <=> PRPP + adenine) 0 0.020085 38 LMOMA output 1 CAETHG_1371 Adenosine 5'-monophosphate phosphohydrolase (H2O + AMP <=> phosphate + H+ + adenosine) 0 0.020085 39 LMOMA output 1 CAETHG_3924 O-ribose-1,5-phosphomutase (ribose-1-phosphate <=> ribose-5phosphate) 0 0.020085 40 LMOMA output 1 CAETHG_0160 N-ribosylnicotinamide:opτoφocφaτpibosyltransφerase (phosphate + N-ribosylnicotinamide <=> nicotinamide + ribose-1phosphate) 0 0.020085 41 LMOMA output 1 CAETHG_2721 Phosphoenolpyruvate carboxykinase (PPCK) (ATP + oxaloacetate + H+ -> ADP + CO2 + phosphoenolpyruvate) 0 0.02007 42 LMOMA output 1 CAETHG_0498 Cystathionine beta-lyase (H2O + cystathionine --> NH3 + pyruvate + homocysteine) 0 0.020055 43 LMOMA output 1 CAETHG_2751 Citramalate synthase (H2O + pyruvate + acetyl-CoA <=> CoA + citramalate) 0 0.020025 44 LMOMA output 2 CAETHG_2909, CAETHG_2932 ATP: pyruvate-orthophosphate phosphotransferase (ATP + phosphate + pyruvate + H+ -> PPi + AMP + phosphoenolpyruvate), alpha-acetolactate decarboxylase (ALCTT -> CO2 + (K)-acetoin) 0 0.020025 45 LMOMA output 1 CAETHG_3021 L-arginine iminohydrolase (H2O + L-arginine <=> NH3 + citrulline) 0 0.02001

Example 20.

This example describes targets of gene disruption that are common to different production pathways. Optimizations were performed using an evolutionary algorithm on 444 paths. Each strain design was evaluated based on the yield achieved (non-growth design) and the yield associated with biomass production (growth design). Each gene was assigned a rank based on its frequency of occurrence in the strain constructs. Nineteen genes were frequently identified for disruption in the optimized strains.

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# Gene Evaluation of pairing with height Score without pairing with growth Overall score 1 CAETHG_3359 6.039281 14.18996 20.22924 2 CAETHG_2932 0 16.79651 16.79651 3 CAETHG_3293 2.508019 13.12476 15.63278 4 CAETHG_351O 0 12.77112 12.77112 5 CAETHG_3924 0 11.15045 11.15045 6 CAETHG_1371 0 11.03476 11.03476 7 CAETHG_2006 0 10.68385 10.68385 8 CAETHG_29O9 1.515088 8.61957 10.13466 9 CAETHG_2721 0 9.82919 9.82919 10 CAETHG_2753 0.50272 9.082944 9.585664 eleven CAETHG_0160 0 8.767024 8.767024 12 CAETHG_3299 0 7.876761 7.876761 13 CAETHG_2751 4.149778 3.457399 7.607177 14 CAETHG_O233 0 7.516631 7.516631 15 CAETHG_127O 0 7.501854 7.501854 16 CAETHG_0234 0 7.213378 7.213378 17 CAETHG_279O 0 6.668087 6.668087 18 CAETHG_2791 0 6.554927 6.554927 19 CAETHG_2796 0 6.324132 6.324132

Example 21.

This example describes gene disruption targets to increase production of the target compound during autotrophic growth. This strategy involves eliminating or reducing the production of other fermentation byproducts, making the target compound a necessary growth byproduct. Metabolic modeling experiments were performed as described in Example 1.

Simulation data demonstrate that this strategy is suitable for target compounds whose production results in minimal ATP load. This strategy is not very suitable for products with a significant ATP load during autotrophic growth. This is because this strategy reduces cellular ATP output by eliminating substrate-level phosphorylation catalyzed by acetate kinase.

In particular, the production of products such as acetone, isopropanol, 1,3butanediol, 3-hydroxybutyrate, 2-hydroxyisobutyrate, 3-hydroxyisovalerate and adipic acid can be improved by introducing a disruptive mutation into the genes encoding acetate kinase and/or phosphate transacetylase and, optionally, additionally introducing a disruptive mutation in one or more genes encoding acetolactate decarboxylase, lactate dehydrogenase, aldehyde dehydrogenase or citramalate synthase.

Each model was evaluated using flux variability analysis, determining the minimum required flux to the target junction during normal growth. The proposed set of gene mutations leading to disorders was then applied to each model. The flux variability analysis was repeated to determine if there was any coupling between compound production and growth. Simulations were performed using cobrapy version 0.13.4.

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Product Minimum yield during cell growth Minimum yield when growing cells with disrupted target genes Acetone 0.00 0.301 1,3-Butanediol 0.00 0.323 3-hydroxybutyrate 0.00 0.395 2-hydroxy isobutyrate 0.00 0.395 3-hydroxy isovalerate 0.00 0.368 Adipic acid 0.00 0.428

Example 22.

This example describes an increase in the production of the target compound during autotrophic growth in gas mixtures with a low proportion of CO by reducing the required co-production of acetate. Metabolic modeling experiments were performed as described in Example 1.

The strategy involves regulating the equilibrium of redox cofactors and ensuring an excess of NADPH. To maintain redox homeostasis, the cell must synthesize products whose production pathway requires NADPH. Since acetate production does not meet these requirements, the cell must produce other products to achieve maximum growth rates.

Simulation data demonstrate that this strategy is suitable for ATP-loaded target compounds requiring acetate coproduction. This strategy is also suitable for strains producing ethanol as a major product. This strategy is expected to work in low CO gases, where the cell can use hydrogenase to reduce ferredoxin and NAD(P)+. In some cases, the maximum possible yield of the target compound will be reduced because this strategy reduces the efficiency of the cell's energy metabolism.

In particular, the production of products such as ethanol, acetone, isopropanol, 1,3-butanediol, 2-butanol, 2-hydroxyisobutyrate, 3-hydroxyisovalerate, adipic acid, methyl ethyl ketone, isoprene, salicylate, chorismate and farnesene can be improved by introducing mutations leading to disorder in the gene encoding NAD-dependent electron bifurcation [FeFe] hydrogenase (eg, Hyd), and optionally further introducing disorder mutations in one or more genes encoding glutamate synthase, citramalate synthase, acetolactate decarboxylase, or lactate dehydrogenase.

Each model was evaluated using flux variability analysis, determining the minimum required flux to acetate at high growth rates. The proposed set of gene mutations leading to disorders was then applied to each model. NAD-dependent hydrogenase (Hyd) was removed from the stoichiometric matrix to represent a knockout of this enzyme. The flux through the glutamate synthase reaction was reduced by 30% to represent disruption of this enzyme. The flow variability analysis was repeated to determine the minimum acetate production requirements to achieve maximum growth. Simulations were performed using cobrapy version 0.13.4._______

Minimum required acetate yield at maximum growth rate (C-mol of product/mol of CO + H ₂ uptake) Product Parent strain Impaired NAD-dependent electron- bifurcation [FeFe]hydrogenase (Hyd) Impaired NAD-dependent electron bifurcation [FeFeJ-hydrogenase (Hyd) and impaired glutamate synthase (when expressed) Ethanol 0.430 0.356 0.0002 Acetone 0.430 0.356 0.0002 Isopropanol 0.430 0.356 0.0002 1,3-Butanediol 0.430 0.356 0.0000 2-buta nol 0.430 0.356 0.0002 2-hydroxy isobutyrate 0.430 0.356 0.0000 3-hydroxy isovalerate 0.430 0.356 0.0000 Adipic acid 0.430 0.356 0.0002 Methyl ethyl ketone 0.430 0.356 0.0002 Isoprene 0.430 0.355 0.0000 Salicylate 0.430 0.356 0.0002 Khorismat 0.430 0.356 0.0002 Farnesene 0.430 0.356 0.0002

Example 23.

This example describes an increase in flux through acetoacetyl-CoA, a central metabolic hub. Increasing the flow through this unit will increase the production of products in the following stages, for example, acetone, isopropyl alcohol, 3-hydroxyisovaleryl-CoA, 3hydroxyisovalerate, isobutylene, isopentenyl pyrophosphate (IPP), dimethylallyl pyrophosphate

- 204 044153 (DMAPP), isoprene, terpenoids, e.g. farnesene, 3-hydroxybutyryl-CoA, crotonyl-CoA, 3-hydroxybutyrate, 3-hydroxybutyrylaldehyde, 1,3-butanediol, 2-hydroxyisobutyryl-CoA, 2hydroxyisobutyrate, butyryl-CoA, butyrate , butanol, caproate, hexanol, octanoate, octanol, 1,3hexanediol, 2-buten-1-ol, isovaleryl-CoA, isovalerate or isoamyl alcohol. Metabolic modeling experiments were performed as described in Example 1.

Most Wood-Ljungdahl microorganisms are not capable of naturally converting acetyl-CoA to acetoacetyl-CoA, so the introduction of a heterologous enzyme such as a thiolase (i.e. acetyl-CoA acetyltransferase) may be required at this stage (EC 2.3.1.9). The thiolase may be, for example, Th1A from Clostridium acetobutylicum (WP_010966157.1), PhaA from Cupriavidus necator (WP013956452.1), BktB from Cupriavidus necator (WP011615089.1), AtoB from Escherichia coli (NP_416728.1) or a similar enzyme.

In particular, it is possible to improve the flux through acetoacetyl-CoA by introducing disruptive mutations in one or more genes encoding one or more, two or more, three or more, four or more, or five or more of the NAD-dependent electron -bifurcating [FeFe]-hydrogenase (e.g. Hyd), glutamate synthase, citramalate synthase, acetolactate decarboxylase, lactate dehydrogenase, acetate kinase, phosphate transacetylase or aldehyde dehydrogenase._________________________

Enzyme name Account number in C. autothanogenum NAD-dependent electron- bifurcation [FeFeJ-hydrogenase CAETHG_1576, CAETHG_1578, CAETHG_3569, CAETHG_357O, CAETHG_3571 Glutamate synthase CAETHG_0477, CAETHG_1580, CAETHG_385O, CAETHG_3851 Citramalate synthase CAETHG_2751 Acetolactate decarboxylase CAETHG_2932 Lactate dehydrogenase CAETHG_1147 Acetate kinase CAETHG_3359 Phosphate transacetylase CAETHG_3358 Aldehyde dehydrogenase CAETHG_1819, CAETHG_3287, CAETHG_1830

All sources, including publications, patent applications and patents cited herein, are incorporated herein by reference to the same extent as if each source had been separately and specifically identified for inclusion by reference and set forth herein in its entirety. volume. The mention of any prior art in this application is not, and should not be construed as, an admission that the prior art forms part of the generally known general knowledge in the field in question in any country.

The use of singular forms and similar designations in the context of the description of the present invention (especially in the context of the following claims) should be considered to include both the singular and plural unless otherwise indicated herein or the context clearly contradicts it. The terms consisting of, having, including, and containing are to be considered non-limiting terms (i.e., including, but not limited to), unless otherwise noted. The term consisting essentially of limits the essence of the composition, process or method to specified materials or steps or materials or steps that do not significantly affect the basic and novel characteristics of the composition, process or method. The use of an alternative (for example, or) should be understood to mean one alternative, both alternatives, or any combination of alternatives. As used herein, the term approximately means ±20% of the stated range, value, or structure unless otherwise noted.

The listing of ranges of values herein is intended solely as a shorthand way of referring to each individual value falling within such range, unless otherwise stated herein, and each individual value is included herein as if it were separately listed in this document. For example, any concentration range, percentage range, ratio range, integer range, size range, or thickness range should be understood to include the value of any integer within the range and, where appropriate, fractions thereof (e.g., one tenth and one hundredth of an integer ), unless otherwise specified.

All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly inconsistent with the context. The use of any examples or exemplary statements (such as) provided herein is intended solely to better illuminate the present invention and is not intended to limit the spirit of the present invention unless otherwise stated. Nothing contained in this application should be construed as indicating any element not contained in the claims as being necessary for the practice of the present invention.

Preferred embodiments of the present invention are described herein. Variations of such preferred embodiments may become apparent to those skilled in the art.

- 205 044153 of the art after reading the above description. The present inventors expect that those skilled in the art will employ such embodiments as appropriate, and the present inventors expect that they will be practiced differently than specifically described herein. Accordingly, the present invention includes all modifications and equivalents of the subject matter set forth in the appended claims, as provided by applicable law. In addition, any combination of the elements described above in all possible variations is included in the present invention, unless otherwise indicated herein or otherwise clearly contrary to the context.

Claims (5)

1. A non-naturally occurring Wood-Ljungdahl bacterium, which is a bacterium Clostridium autoethanogenum containing a heterologous thiolase and a mutation causing disturbances in one or more genes encoding one or more of the NAD-dependent electron bifurcation [FeFe] hydrogenase, glutamate synthase, citramalate synthase, acetolactate decarboxylase, lactate dehydrogenase, acetate kinase, phosphate transacetylase and aldehyde dehydrogenase, the non-natural bacterium having improved carbon flux through acetoacetyl-CoA compared to the wild type bacterium. 2. A non-natural bacterium according to claim 1, producing a product selected from the group consisting of acetone, isopropanol, 3-hydroxyisovaleryl-CoA, 3-hydroxyisovalerate, isobutylene, isopentenyl pyrophosphate, dimethylallyl pyrophosphate, isoprene, farnesene, 3-hydroxybutyryl-CoA , crotonyl-CoA, 3-hydroxybutyrate, 3-hydroxybutyrylaldehyde, 1,3-butanediol, 2hydroxyisobutyryl-CoA, 2-hydroxyisobutyrate, butyryl-CoA, butyrate, butanol, caproate, hexanol, octanoate, octanol, 1,3-hexanediol, 2 -buten-1-ol, isovaleryl-CoA, isovalerate or isoamyl alcohol. 3. A non-naturally occurring bacterium according to claim 1, characterized in that: (a) NAD-dependent electron bifurcation [FeFe] hydrogenase selected from the group consisting of CAETHG_1576, CAETHG_1578, CAETHG_3569, CAETHG_3570 and CAETHG_3571, (b) glutamate synthase selected from the group consisting of CAETHG_0477, CAETHG_1580, CAETHG_3850 and CAETHG_3851, (c ) citramalate synthase is CAETHG_2751, (d) acetolactate decarboxylase is CAETHG_2932, (e) lactate dehydrogenase is CAETHG_1147, (f) acetate kinase is CAETHG_3359, (g) phosphate transacetylase is CAETHG_3358, or (h) aldehyde dehydrogenase selected from the group consisting of CAETHG_1819, CAETHG_3287 and CAETHG_1830. 4. A method for obtaining a product by cultivating a non-natural bacterium according to claim 1 in the presence of a gaseous substrate that contains CO and/or CO ₂ and may contain H ₂ . 5. The method according to claim 4, characterized in that the product is selected from the group consisting of acetone, isopropanol, 3-hydroxyisovaleryl-CoA, 3-hydroxyisovalerate, isobutylene, isopentenylpyrophosphate, dimethylallylpyrophosphate, isoprene, farnesene, 3-hydroxybutyryl-CoA, crotonyl -CoA, 3-hydroxybutyrate, 3-hydroxybutyrylaldehyde, 1,3-butanediol, 2-hydroxyisobutyryl-CoA, 2hydroxyisobutyrate, butyryl-CoA, butyrate, butanol, caproate, hexanol, octanoate, octanol, 1,3hexanol, 2-buten-1-ol , isovaleryl-CoA, isovalerate or isoamyl alcohol.