Journal
BIORESOURCE TECHNOLOGY
Volume 218, Issue -, Pages 999-1007Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biortech.2016.07.066
Keywords
Microorganisms; CRISPRi; Gene repressing; Plant natural products; Low-cost production
Funding
- Natural Science Foundation of Jiangsu Province in China [BK20160718]
- Fundamental Research Funds for the Central Universities in China [KYZ201654]
- Priority Academic Program Development of Jiangsu Higher Education Institutions in China (PAPD)
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Microbial fermentations promise to revolutionize the conventional extraction of (2S)-pinocembrin from natural plant sources. Previously an Escherichia coli fermentation system was developed for one-step (2S)-pinocembrin production. However, this fermentation platform need supplementation of expensive malonyl-CoA precursor malonate and requires morpholinopropane sulfonate to provide buffering capacity. Here, a clustered regularly interspaced short palindromic repeats interference was constructed to efficiently channel carbon flux toward malonyl-CoA. By exploring the effects of different culture pH on microbial fermentation, it was found that high pH values favored upstream pathway catalysis, while low pH values favored downstream pathway catalysis. Based on this theory, a two-stage pH control strategy was proposed. The pH was controlled at 7.0 during 0-10 h, and was shifted to 6.5 after 10 h. Finally, the (2S)-pinocembrin titers increased to 525.8 mg/L. These results were attained in minimal medium without additional precursor supplementation, thus offering opportunities for industrial scale low-cost production of flavonoids. (C) 2016 Elsevier Ltd. All rights reserved.
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