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Engineering cofacto...
Engineering cofactor supply and recycling to drive phenolic acid biosynthesis in yeast
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- Chen, Ruibing (author)
- Chinese Academy of Sciences
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- Gao, Jiaoqi (author)
- Chinese Academy of Sciences
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- Yu, Wei (author)
- Chinese Academy of Sciences
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- Chen, Xianghui (author)
- Shanghai University
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- Zhai, Xiaoxin (author)
- Chinese Academy of Sciences
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- Chen, Yu, 1990 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Zhang, Lei (author)
- Nantong University,Shanghai University
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- Zhou, Yongjin, 1984 (author)
- Chinese Academy of Sciences
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(creator_code:org_t)
- 2022-04-28
- 2022
- English.
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In: Nature Chemical Biology. - : Springer Science and Business Media LLC. - 1552-4450 .- 1552-4469. ; 18:5, s. 520-529
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Abstract
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- Advances in synthetic biology enable microbial hosts to synthesize valuable natural products in an efficient, cost-competitive and safe manner. However, current engineering endeavors focus mainly on enzyme engineering and pathway optimization, leaving the role of cofactors in microbial production of natural products and cofactor engineering largely ignored. Here we systematically engineered the supply and recycling of three cofactors (FADH2, S-adenosyl-l-methion and NADPH) in the yeast Saccharomyces cerevisiae, for high-level production of the phenolic acids caffeic acid and ferulic acid, the precursors of many pharmaceutical molecules. Tailored engineering strategies were developed for rewiring biosynthesis, compartmentalization and recycling of the cofactors, which enabled the highest production of caffeic acid (5.5 ± 0.2 g l−1) and ferulic acid (3.8 ± 0.3 g l−1) in microbial cell factories. These results demonstrate that cofactors play an essential role in driving natural product biosynthesis and the engineering strategies described here can be easily adopted for regulating the metabolism of other cofactors. [Figure not available: see fulltext.].
Subject headings
- TEKNIK OCH TEKNOLOGIER -- Maskinteknik -- Produktionsteknik, arbetsvetenskap och ergonomi (hsv//swe)
- ENGINEERING AND TECHNOLOGY -- Mechanical Engineering -- Production Engineering, Human Work Science and Ergonomics (hsv//eng)
- TEKNIK OCH TEKNOLOGIER -- Maskinteknik -- Annan maskinteknik (hsv//swe)
- ENGINEERING AND TECHNOLOGY -- Mechanical Engineering -- Other Mechanical Engineering (hsv//eng)
- NATURVETENSKAP -- Biologi -- Mikrobiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Microbiology (hsv//eng)
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- art (subject category)
- ref (subject category)
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- By the author/editor
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Chen, Ruibing
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Gao, Jiaoqi
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Yu, Wei
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Chen, Xianghui
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Zhai, Xiaoxin
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Chen, Yu, 1990
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show more...
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Zhang, Lei
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Zhou, Yongjin, 1 ...
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- About the subject
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- ENGINEERING AND TECHNOLOGY
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ENGINEERING AND ...
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and Mechanical Engin ...
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and Production Engin ...
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- ENGINEERING AND TECHNOLOGY
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ENGINEERING AND ...
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and Mechanical Engin ...
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and Other Mechanical ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Microbiology
- Articles in the publication
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Nature Chemical ...
- By the university
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Chalmers University of Technology