Hyperproduction of 3-hydroxypropionate by Halomonas bluephagenesis

被引:67
|
作者
Jiang, Xiao-Ran [1 ,2 ]
Yan, Xu [2 ,3 ]
Yu, Lin-Ping [2 ]
Liu, Xin-Yi [2 ,3 ]
Chen, Guo-Qiang [2 ,3 ,4 ]
机构
[1] Army Med Univ, Dept Microbiol, Chongqing, Peoples R China
[2] Tsinghua Univ, Sch Life Sci, Beijing, Peoples R China
[3] Tsinghua Univ, Ctr Synthet & Syst Biol, Sch Life Sci, Beijing, Peoples R China
[4] Tsinghua Univ, Dept Chem Engn, MOE Key Lab Ind Biocatalysis, Beijing, Peoples R China
基金
中国国家自然科学基金; 欧盟地平线“2020”; 中国博士后科学基金;
关键词
LOW-COST PRODUCTION; ACID PRODUCTION; ESCHERICHIA-COLI; GLYCEROL; BIOSYNTHESIS; TD01; POLY(3-HYDROXYPROPIONATE-CO-4-HYDROXYBUTYRATE); 1,3-PROPANEDIOL; DEHYDRATASE; METABOLISM;
D O I
10.1038/s41467-021-21632-3
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
3-Hydroxypropionic acid (3HP), an important three carbon (C3) chemical, is designated as one of the top platform chemicals with an urgent need for improved industrial production. Halomonas bluephagenesis shows the potential as a chassis for competitive bioproduction of various chemicals due to its ability to grow under an open, unsterile and continuous process. Here, we report the strategy for producing 3HP and its copolymer poly(3-hydroxybutyrate-co-3-hydroxypropionate) (P3HB3HP) by the development of H. bluephagenesis. The transcriptome analysis reveals its 3HP degradation and synthesis pathways involving endogenous synthetic enzymes from 1,3-propanediol. Combing the optimized expression of aldehyde dehydrogenase (AldD(Hb)), an engineered H. bluephagenesis strain of whose 3HP degradation pathway is deleted and that overexpresses alcohol dehydrogenases (AdhP) on its genome under a balanced redox state, is constructed with an enhanced 1.3-propanediol-dependent 3HP biosynthetic pathway to produce 154gL(-1) of 3HP with a yield and productivity of 0.93gg(-1) 1,3-propanediol and 2.4gL(-1) h(-1), respectively. Moreover, the strain could also accumulate 60% poly(3-hydroxybutyrate-co-32-45% 3-hydroxypropionate) in the dry cell mass, demonstrating to be a suitable chassis for hyperproduction of 3HP and P3HB3HP. 3-Hydroxypropionic acid (3HP) is an important platform chemical. Here, the authors engineer Halomonas bluephagenesis by deleting newly identified degradation pathway and balancing redox state to achieve high level production of 3HP and its copolymer under open and unsterile conditions.
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页数:13
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