期刊
METABOLIC ENGINEERING
卷 17, 期 -, 页码 42-50出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ymben.2013.02.002
关键词
beta-Carotene; Terpenoids; Cofactor; NADPH; Escherichia coli
资金
- National High Technology Research and Development Program of China [2012AA023104]
- National Basic Research Program of China [2011CBA00806]
- Tianjin Key Technology R&D program of Tianjin Municipal Science and Technology Commission
- Hundred Talent Program of the Chinese Academy of Sciences
ATP and NADPH are two important cofactors for production of terpenoids compounds. Here we have constructed and optimized beta-carotene synthetic pathway in Escherichia coli, followed by engineering central metabolic modules to increase ATP and NADPH supplies for improving beta-carotene production. The whole beta-carotene synthetic pathway was divided into five modules. Engineering MEP module resulted in 3.5-fold increase of beta-carotene yield, while engineering beta-carotene synthesis module resulted in another 3.4-fold increase. The best beta-carotene yield increased 21%, 17% and 39% after modulating single gene of ATP synthesis, pentose phosphate and TCA modules, respectively. Combined engineering of TCA and PPP modules had a synergistic effect on improving beta-carotene yield, leading to 64% increase of beta-carotene yield over a high producing parental strain. Fed-batch fermentation of the best strain CAR005 was performed, which produced 2.1 g/L beta-carotene with a yield of 60 mg/g DCW. (C) 2013 Elsevier Inc. All rights reserved.
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