Title:
GENETICALLY ENGINEERED STRAIN HAVING HIGH-YIELD OF L-VALINE AND METHOD FOR PRODUCING L-VALINE BY FERMENTATION
Document Type and Number:
WIPO Patent Application WO/2021/077455
Kind Code:
A1
Abstract:
A genetically engineered strain having high-yield of L-valine. Starting from Escherichia coli W3110, the acetolactate synthase gene alsS of Bacillus subtilis is integrated and strongly expressed on a genome thereof; the Escherichia coli ppGpp 3'-pyrophosphate hydrolase mutant R290E/K292D gene spoT is integrated and strongly expressed on the genome thereof; the lactate dehydrogenase gene ldhA, the pyruvate formate lyase I gene pflB, and the genes frdA, frdB, frdC, frdD of four subunits of the fumaric acid reductase on the genome thereof is knocked out; the branched chain amino acid transaminase gene ilvE of Escherichia coli is replaced with the leucine dehydrogenase gene bcd of Bacillus subtilis; and the acetylhydroxylate isomerase reductase gene ilvC of Escherichia coli is replaced with the encoding gene of the mutant L67E/R68F/K75E. Furthermore, the L-valine fermentation method is improved, and the L-valine yield and the sugar acid conversion rate are increased by using a two-stage oxygen dissolution control.
Inventors:
XIE XIXIAN (CN)
LIU XIAOQIAN (CN)
HAO YANAN (CN)
MEN JIAXUAN (CN)
LIU YINING (CN)
LI XUAN (CN)
TIAN DAOGUANG (CN)
WEN CHENHUI (CN)
XIONG BO (CN)
LIU XIAOQIAN (CN)
HAO YANAN (CN)
MEN JIAXUAN (CN)
LIU YINING (CN)
LI XUAN (CN)
TIAN DAOGUANG (CN)
WEN CHENHUI (CN)
XIONG BO (CN)
Application Number:
PCT/CN2019/114288
Publication Date:
April 29, 2021
Filing Date:
October 30, 2019
Export Citation:
Assignee:
UNIV TIANJIN SCIENCE & TECH (CN)
International Classes:
C12N15/70; C12N1/21; C12P13/08; C12R1/19
Domestic Patent References:
| WO2013175428A2 | 2013-11-28 |
Foreign References:
| CN105296410A | 2016-02-03 | |||
| CN108913642A | 2018-11-30 | |||
| CN106520651A | 2017-03-22 |
Other References:
JIN HWAN PARK, KWANG HO LEE, TAE YONG KIM, SANG YUP LEE: "Metabolic engineering of Escherichia coli for the production of L-valine based on transcriptome analysis and in silico gene knockout simulation.", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, NATIONAL ACADEMY OF SCIENCES, US, vol. 104, no. 19, 8 May 2007 (2007-05-08), US, pages 7797 - 7802, XP002711681, ISSN: 0027-8424, DOI: 10.1073/PNAS.0702609104
SOINI JAAKKO; FALSCHLEHNER CHRISTINA; LIEDERT CHRISTINA; BERNHARDT JÖRG; VUORISTO JUSSI; NEUBAUER PETER: "Norvaline is accumulated after a down-shift of oxygen in Escherichia coli W3110", MICROBIAL CELL FACTORIES, vol. 7, no. 1, 21 October 2008 (2008-10-21), pages 30, XP021043553, ISSN: 1475-2859, DOI: 10.1186/1475-2859-7-30
PARK JIN HWAN, JANG YU-SIN, LEE JEONG WOOK, LEE SANG YUP: "Escherichia coli W as a new platform strain for the enhanced production of L-Valine by systems metabolic engineering", BIOTECHNOLOGY AND BIOENGINEERING, WILEY, US, vol. 108, no. 5, 1 May 2011 (2011-05-01), US, pages 1140 - 1147, XP055804146, ISSN: 0006-3592, DOI: 10.1002/bit.23044
LI YLIN ZHUANG C ET AL.: "Metabolic engineering of Escherichia coli using CRISPR-Cas9 meditated genome editing", METABOLIC ENGINEERING, vol. 31, 2015, pages 13 - 21
SOINI JAAKKO; FALSCHLEHNER CHRISTINA; LIEDERT CHRISTINA; BERNHARDT JÖRG; VUORISTO JUSSI; NEUBAUER PETER: "Norvaline is accumulated after a down-shift of oxygen in Escherichia coli W3110", MICROBIAL CELL FACTORIES, vol. 7, no. 1, 21 October 2008 (2008-10-21), pages 30, XP021043553, ISSN: 1475-2859, DOI: 10.1186/1475-2859-7-30
PARK JIN HWAN, JANG YU-SIN, LEE JEONG WOOK, LEE SANG YUP: "Escherichia coli W as a new platform strain for the enhanced production of L-Valine by systems metabolic engineering", BIOTECHNOLOGY AND BIOENGINEERING, WILEY, US, vol. 108, no. 5, 1 May 2011 (2011-05-01), US, pages 1140 - 1147, XP055804146, ISSN: 0006-3592, DOI: 10.1002/bit.23044
LI YLIN ZHUANG C ET AL.: "Metabolic engineering of Escherichia coli using CRISPR-Cas9 meditated genome editing", METABOLIC ENGINEERING, vol. 31, 2015, pages 13 - 21
Attorney, Agent or Firm:
BEIJING RISINGMARK INTELLECTUAL PROPERTY AGENCY (CN)
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