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Metab Eng. 2013 May;17:42-50. doi: 10.1016/j.ymben.2013.02.002. Epub 2013 Mar 7.

Engineering central metabolic modules of Escherichia coli for improving β-carotene production.

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Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China.


ATP and NADPH are two important cofactors for production of terpenoids compounds. Here we have constructed and optimized β-carotene synthetic pathway in Escherichia coli, followed by engineering central metabolic modules to increase ATP and NADPH supplies for improving β-carotene production. The whole β-carotene synthetic pathway was divided into five modules. Engineering MEP module resulted in 3.5-fold increase of β-carotene yield, while engineering β-carotene synthesis module resulted in another 3.4-fold increase. The best β-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 β-carotene yield, leading to 64% increase of β-carotene yield over a high producing parental strain. Fed-batch fermentation of the best strain CAR005 was performed, which produced 2.1g/L β-carotene with a yield of 60mg/g DCW.

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