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Method for efficiently producing 3-hydroxypropionic acid(3HP) and derivatives thereof based on halophilic bacteria

A technology of hydroxypropionic acid and hydroxypropionate, which is applied in the field of microbial metabolic engineering and fermentation engineering, and can solve the problems of decreased cell viability and increased 3HP production

Active Publication Date: 2020-09-25
TSINGHUA UNIV
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Problems solved by technology

3HP is cytotoxic at high concentrations, which will lead to decreased cell viability and limit the continued increase of 3HP production in the later stages of fermentation (Chun, A.Y., et al., Elucidation of toxicity of organic acids inhibiting growth of Escherichia coli W. Biotechnology and bioprocessing engineering, 2014.19( 5): p.858-865.)

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  • Method for efficiently producing 3-hydroxypropionic acid(3HP) and derivatives thereof based on halophilic bacteria
  • Method for efficiently producing 3-hydroxypropionic acid(3HP) and derivatives thereof based on halophilic bacteria
  • Method for efficiently producing 3-hydroxypropionic acid(3HP) and derivatives thereof based on halophilic bacteria

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[0024] Polyhydroxyalkanoates (Polyhydroxyalkanoates, PHA) are a class of biodegradable bio-based plastics, among which poly 3-hydroxypropionate (P3HP) has the best mechanical properties in PHA, and its monomer 3-hydroxypropyl Acid (3-hydroxypropionic acid, 3HP) is also an important platform compound, one of the 12 most valuable platform compounds listed by the US Department of Energy. However, there is no report that natural microorganisms can synthesize P3HP. Most of its biosynthesis is to construct heterologously expressed metabolic pathways in general-purpose chassis strains such as E. coli. However, E. coli has the disadvantage of being easily contaminated in the industrial production process. And the halomonas (particularly Halomonas bluephagenesisTD) that the present invention utilizes can carry out continuous open fermentation, does not need to sterilize in the whole fermentation process, and is not easy to infect bacteria and other characteristics, combined with the nor...

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Abstract

A 3-hydroxypropionic acid(3HP) degradation way of halophilic bacteria is analyzed for the first time by a transcriptomics method, the inventor finds that the 3-hydroxypropionic acid can degrade genesdddA and dddC, and recombination halophilic bacteria TD delta dddA which cannot degrade 3HP is obtained. Based on this, an alcohol dehydrogenase gene AdhP and an aldehyde dehydrogenase gene AldDTD, which are from the halophilic bacteria endogenous and responsible for production and metabolism of the 3HP are further utilized, and a synthetizing biology means is taken for adjusting and controlling the expression level of the metabolic way. Through screening, the recombination halophilic bacteria high in yield of the 3HP is obtained, and the yield and the productivity are respectively 0.93g / g ofthe 1,3-propylene glycol(PDO) and 2.4g / L / h, which are the highest 3HP yield and productivity reported so far.

Description

technical field [0001] The invention relates to the fields of microbial metabolism engineering and fermentation engineering. More specifically, the present invention analyzes and deletes the degradation pathway of 3-hydroxypropionic acid by constructing the synthesis pathway of 3-hydroxypropionic acid (3HP) and its derivatives in halophilic bacteria, enhances the metabolic flow of the target product, and regulates the Redox balance, so as to realize the purpose of producing 3-hydroxypropionic acid and its derivatives (polymers) by anti-staining halophilic bacteria. Background technique [0002] 3-hydroxypropionic acid (3-hydroxypropionic acid, 3HP) is an important platform compound, which ranks among the 12 most valuable platform compounds listed by the U.S. Department of Energy (Wang, Y., et al., Biosynthesis of platform chemical 3-hydroxypropionic acid (3HP) directly from CO 2 incyanobacterium Synechocystis sp. PCC 6803. Metabolic engineering, 2016.34: p.60-70.). 3-Hyd...

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N1/21C12N15/74C12N15/90C12N15/53C12N15/52C12N15/54C12P7/42C12P7/62C12R1/01
CPCC12N15/52C12N9/0006C12N9/0008C12N9/93C12N9/1029C12N15/74C12N15/902C12P7/42C12P7/625C12Y101/99001C12Y102/01027C12Y101/01202C12Y102/01003C12Y102/01004C12Y102/01005C12Y101/01001C12Y602/01C12Y203/01194
Inventor 陈国强蒋笑然闫煦
Owner TSINGHUA UNIV
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