WO2002029032A3 - Whole cell engineering by mutagenizing a substantial portion of a starting genome, combining mutations, and optionally repeating - Google Patents

Whole cell engineering by mutagenizing a substantial portion of a starting genome, combining mutations, and optionally repeating Download PDF

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Publication number
WO2002029032A3
WO2002029032A3 PCT/US2001/031004 US0131004W WO0229032A3 WO 2002029032 A3 WO2002029032 A3 WO 2002029032A3 US 0131004 W US0131004 W US 0131004W WO 0229032 A3 WO0229032 A3 WO 0229032A3
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WO
WIPO (PCT)
Prior art keywords
provides
novel
methods
gene
mutagenizing
Prior art date
Application number
PCT/US2001/031004
Other languages
French (fr)
Other versions
WO2002029032A2 (en
Inventor
Jay M Short
Pengcheng Fu
Martin Latterich
Jing Wei
Michael Levin
Original Assignee
Diversa Corp
Jay M Short
Pengcheng Fu
Martin Latterich
Jing Wei
Michael Levin
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US09/677,584 external-priority patent/US7033781B1/en
Priority claimed from PCT/US2001/019367 external-priority patent/WO2001096551A2/en
Application filed by Diversa Corp, Jay M Short, Pengcheng Fu, Martin Latterich, Jing Wei, Michael Levin filed Critical Diversa Corp
Priority to AU2002211402A priority Critical patent/AU2002211402A1/en
Priority to JP2002532602A priority patent/JP2004536553A/en
Priority to DE01979431T priority patent/DE01979431T1/en
Priority to CA002424178A priority patent/CA2424178A1/en
Priority to IL15515401A priority patent/IL155154A0/en
Priority to EP01979431A priority patent/EP1415160A2/en
Priority to US10/398,271 priority patent/US20050124010A1/en
Publication of WO2002029032A2 publication Critical patent/WO2002029032A2/en
Publication of WO2002029032A3 publication Critical patent/WO2002029032A3/en

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/1034—Isolating an individual clone by screening libraries
    • C12N15/1089—Design, preparation, screening or analysis of libraries using computer algorithms
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/102—Mutagenizing nucleic acids
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/102—Mutagenizing nucleic acids
    • C12N15/1027—Mutagenizing nucleic acids by DNA shuffling, e.g. RSR, STEP, RPR
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/1034—Isolating an individual clone by screening libraries
    • C12N15/1058—Directional evolution of libraries, e.g. evolution of libraries is achieved by mutagenesis and screening or selection of mixed population of organisms
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/82—Vectors or expression systems specially adapted for eukaryotic hosts for plant cells, e.g. plant artificial chromosomes (PACs)
    • C12N15/8241—Phenotypically and genetically modified plants via recombinant DNA technology
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/531—Production of immunochemical test materials
    • G01N33/532—Production of labelled immunochemicals
    • G01N33/534—Production of labelled immunochemicals with radioactive label
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6803—General methods of protein analysis not limited to specific proteins or families of proteins
    • G01N33/6848—Methods of protein analysis involving mass spectrometry
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biotechnology (AREA)
  • Molecular Biology (AREA)
  • General Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Physics & Mathematics (AREA)
  • Immunology (AREA)
  • General Health & Medical Sciences (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Plant Pathology (AREA)
  • Bioinformatics & Computational Biology (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Cell Biology (AREA)
  • Analytical Chemistry (AREA)
  • Pathology (AREA)
  • General Physics & Mathematics (AREA)
  • Medicinal Chemistry (AREA)
  • Food Science & Technology (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Ecology (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

An invention comprising cellular transformation, directed evolution, and screening methods for creating novel transgenic organisms having desirable properties. In one embodiment, this invention provides a method of generating a transgenic organism, such as a microbe or a plant, having a plurality of traits that are differentially activatable. This invention also provides a method of retooling genes and gene pathways by the introduction of regulatory sequences, such as promoters, that are operable in an intended host, this conferring operability to a novel gene pathway when it is introduced into an intended host. For example a novel man-made gene pathway, generated based on microbially-derived progenitor templates, that is operable in a plant cell. This invention also provides a method of generating novel host organisms having increased expression of desirable traits, recombinant genes, and gene products. This invention provides novel methods for determining polypeptide profiles, and protein expression variations, which methods are applicable to all sample types disclosed herein. The present invention provides methods of simultaneously identifying and quantifying individual proteins in complex protein mixtures. Additionally this invention provides methods for cellular and metabolic engineering of new and modified phenotypes by using 'on-line' or 'real-time' metabolic flux analysis.
PCT/US2001/031004 2000-09-30 2001-10-01 Whole cell engineering by mutagenizing a substantial portion of a starting genome, combining mutations, and optionally repeating WO2002029032A2 (en)

Priority Applications (7)

Application Number Priority Date Filing Date Title
AU2002211402A AU2002211402A1 (en) 2000-09-30 2001-10-01 Whole cell engineering by mutagenizing a substantial portion of a starting genome, combining mutations, and optionally repeating
JP2002532602A JP2004536553A (en) 2000-09-30 2001-10-01 Whole-cell engineering by essentially partial mutation of the primordial genome, combination of mutations, and arbitrary repetition
DE01979431T DE01979431T1 (en) 2000-09-30 2001-10-01 CONSTRUCTION OF WHOLE CELLS THROUGH MUTAGENESE OF A SIGNIFICANT PART OF AN INITIAL GENE, COMBINATION OF MUTATIONS AND, IF REQUIRED, REPEAT
CA002424178A CA2424178A1 (en) 2000-09-30 2001-10-01 Whole cell engineering by mutagenizing a substantial portion of a starting genome, combining mutations, and optionally repeating
IL15515401A IL155154A0 (en) 2000-09-30 2001-10-01 Whole cell engineering by mutagenizing a substantial portion of a starting genome, combining mutations, and optionally repeating
EP01979431A EP1415160A2 (en) 2000-09-30 2001-10-01 Whole cell engineering by mutagenizing a substantial portion of a starting genome, combining mutations, and optionally repeating
US10/398,271 US20050124010A1 (en) 2000-09-30 2001-10-01 Whole cell engineering by mutagenizing a substantial portion of a starting genome combining mutations and optionally repeating

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US09/677,584 2000-09-30
US09/677,584 US7033781B1 (en) 1999-09-29 2000-09-30 Whole cell engineering by mutagenizing a substantial portion of a starting genome, combining mutations, and optionally repeating
US27970201P 2001-03-28 2001-03-28
US60/279,702 2001-03-28
US11936701A 2001-06-14 2001-06-14
PCT/US2001/019367 WO2001096551A2 (en) 2000-06-14 2001-06-14 Whole cell engineering by mutagenizing a substantial portion of a starting genome, combining mutations, and optionally repeating
USPCT/US01/19367 2001-06-14

Publications (2)

Publication Number Publication Date
WO2002029032A2 WO2002029032A2 (en) 2002-04-11
WO2002029032A3 true WO2002029032A3 (en) 2004-03-04

Family

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Application Number Title Priority Date Filing Date
PCT/US2001/031004 WO2002029032A2 (en) 2000-09-30 2001-10-01 Whole cell engineering by mutagenizing a substantial portion of a starting genome, combining mutations, and optionally repeating

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US20030044864A1 (en) * 2001-07-20 2003-03-06 Diversa Corporation Cellular engineering, protein expression profiling, differential labeling of peptides, and novel reagents therefor
US7960148B2 (en) 2003-07-02 2011-06-14 Verenium Corporation Glucanases, nucleic acids encoding them and methods for making and using them
CA2535526C (en) 2003-08-11 2015-09-29 Diversa Corporation Laccases, nucleic acids encoding them and methods for making and using them
US20080070291A1 (en) 2004-06-16 2008-03-20 David Lam Compositions and Methods for Enzymatic Decolorization of Chlorophyll
CN103173282A (en) 2004-06-16 2013-06-26 帝斯曼知识产权资产管理有限公司 Compositions and methods for enzymatic decolorization of chlorophyll
US20090038023A1 (en) 2005-03-10 2009-02-05 Verenium Corporation Lyase Enzymes, Nucleic Acids Encoding Them and Methods For Making and Using Them
JP5343212B2 (en) 2005-03-15 2013-11-13 ヴェレニウム コーポレイション Cellulases, nucleic acids encoding them, and methods of making and using them
WO2007005053A1 (en) * 2005-06-30 2007-01-11 Codon Devices, Inc. Hierarchical assembly methods for genome engineering
MY160710A (en) 2006-02-10 2017-03-15 Verenium Corp Cellulolytic enzymes, nucleic acids encoding them and methods for making and using them
CA2638801C (en) 2006-02-14 2016-12-13 Verenium Corporation Xylanases, nucleic acids encoding them and methods for making and using them
CN101437954B (en) 2006-03-07 2015-09-09 嘉吉公司 The nucleic acid of zymohexase and coding zymohexase and their preparation and application
KR101622894B1 (en) 2006-03-07 2016-05-19 바스프 엔자임스 엘엘씨 Aldolases, nucleic acids encoding them and methods for making and using them
CA2649698A1 (en) * 2006-04-17 2007-10-25 Morphotek, Inc. Whole genome evolution technology applied to improve protein and antibody yields by cells
CN101528766A (en) 2006-08-04 2009-09-09 维莱尼姆公司 Glucanases, nucleic acids encoding them and methods for making and using them
NZ598285A (en) 2007-01-30 2013-10-25 Syngenta Participations Ag Enzymes for the treatment of lignocellulosics, nucleic acids encoding them and methods for making and using them
NZ601191A (en) 2007-10-03 2014-01-31 Verenium Corp Xylanases, nucleic acids encoding them and methods for making and using them
CN104651381A (en) 2008-01-03 2015-05-27 巴斯夫酶有限责任公司 Transferases and oxidoreductases, nucleic acids encoding them and methods for making and using them
US11208649B2 (en) 2015-12-07 2021-12-28 Zymergen Inc. HTP genomic engineering platform
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US9988624B2 (en) 2015-12-07 2018-06-05 Zymergen Inc. Microbial strain improvement by a HTP genomic engineering platform
CA3027882A1 (en) * 2016-06-15 2017-12-21 President And Fellows Of Harvard College Methods for rule-based genome design
KR102345898B1 (en) 2016-06-30 2022-01-03 지머젠 인코포레이티드 Methods for generating glucose permeabilization enzyme libraries and uses thereof
WO2018005655A2 (en) 2016-06-30 2018-01-04 Zymergen Inc. Methods for generating a bacterial hemoglobin library and uses thereof
EP3635110A2 (en) * 2017-06-06 2020-04-15 Zymergen, Inc. A high-throughput (htp) genomic engineering platform for improving saccharopolyspora spinosa
WO2018226880A1 (en) * 2017-06-06 2018-12-13 Zymergen Inc. A htp genomic engineering platform for improving escherichia coli
CN110869502A (en) * 2017-06-06 2020-03-06 齐默尔根公司 High throughput transposon mutagenesis
KR20200015916A (en) * 2017-06-06 2020-02-13 지머젠 인코포레이티드 Prioritization of genetic modifications to increase throughput of phenotypic optimization
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WO2020184080A1 (en) * 2019-03-13 2020-09-17 パナソニックＩｐマネジメント株式会社 Information providing method, information providing system, fragrance imparting device, fragrance detection device, and information management device
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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000011208A1 (en) * 1998-08-25 2000-03-02 University Of Washington Rapid quantitative analysis of proteins or protein function in complex mixtures

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000011208A1 (en) * 1998-08-25 2000-03-02 University Of Washington Rapid quantitative analysis of proteins or protein function in complex mixtures

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
GYGI S P ET AL: "QUANTITATIVE ANALYSIS OF COMPLEX PROTEIN MIXTURES USING ISOTOPE-CODED AFFINITY TAGS", NATURE BIOTECHNOLOGY, NATURE PUBLISHING, US, vol. 17, no. 10, October 1999 (1999-10-01), pages 994 - 999, XP001010578, ISSN: 1087-0156 *
JI J ET AL: "Strategy for qualitative and quantitative analysis in proteomics based on signature peptides", JOURNAL OF CHROMATOGRAPHY. BIOMEDICAL APPLICATIONS, ELSEVIER, AMSTERDAM, NL, vol. 745, no. 1, 4 August 2000 (2000-08-04), pages 197 - 210, XP004215299, ISSN: 0378-4347 *
ODA Y ET AL: "ACCURATE QUANTITATION OF PROTEIN EXPRESSION AND SITE-SPECIFIC PHOSPHORYLATION", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA, NATIONAL ACADEMY OF SCIENCE. WASHINGTON, US, vol. 96, no. 12, June 1999 (1999-06-01), pages 6591 - 6596, XP001080471, ISSN: 0027-8424 *
SHEVCHENKO A ET AL: "Rapid 'de Novo' Peptide Sequencing by a Combination of Nanoelectrospray, Isotopic Labeling and a Quadrupole/Time-of-Flight Mass Spectrometer", RAPID COMMUNICATIONS IN MASS SPECTROMETRY, HEYDEN, LONDON, GB, vol. 11, 1997, pages 1015 - 1024, XP002101143, ISSN: 0951-4198 *

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