期刊
NATURE CHEMICAL BIOLOGY
卷 16, 期 11, 页码 1261-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41589-020-0637-3
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资金
- National Natural Science Foundation of China [31870069, 31930085, 21676119]
- National Key Research and Development Program of China [2018YFA0900300, 2018YFA0900504]
- Fundamental Research Funds for the Central Universities [JUSRP51713B]
- BBSRC [BB/R01602X/1]
- BBSRC [BB/R01602X/1] Funding Source: UKRI
Dynamic regulation is a promising strategy for fine-tuning metabolic fluxes in microbial cell factories. However, few of these synthetic regulatory systems have been developed for central carbon metabolites. Here we created a set of programmable and bifunctional pyruvate-responsive genetic circuits for dynamic dual control (activation and inhibition) of central metabolism inBacillus subtilis. We used these genetic circuits to design a feedback loop control system that relies on the intracellular concentration of pyruvate to fine-tune the target metabolic modules, leading to the glucaric acid titer increasing from 207 to 527 mg l(-1). The designed logic gate-based circuits were enabled by the characterization of a new antisense transcription mechanism inB. subtilis. In addition, a further increase to 802 mg l(-1)was achieved by blocking the formation of by-products. Here, the constructed pyruvate-responsive genetic circuits are presented as effective tools for the dynamic control of central metabolism of microbial cell factories.
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