Engineering an Overflow-Responsive Regulation System for Balancing Cellular Redox and Optimizing Microbial Production

IF 3.5 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology and Bioengineering Pub Date : 2025-03-21 DOI:10.1002/bit.28976

Jianli Zhang, Jian Wang, Tian Jiang, Xinyu Gong, Qi Gan, Yuxi Teng, Yusong Zou, Ainoor Anwar Dawadi, Yajun Yan

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引用次数: 0

Abstract

Escherichia coli accumulates acetate as a byproduct in fast growth aerobic conditions when using glucose as carbon source. This phenomenon, known as overflow metabolism, has negative impacts on cell growth and protein expression, also causes carbon loss during biosynthesis in most microbial production scenarios. In this study, we regarded the “waste” metabolite as a useful metabolism indicator, constructed an overflow biosensor to monitor the change of acetate concentration and converted the signal into various regulation outputs. Phloroglucinol is a phenolic compound with several derivatives that exhibit various pharmacological activities. By applying the bifunctional dynamic regulation system on the phloroglucinol production, we released the cellular redox pressure in real-time and reduced the waste of carbon flux on overflow metabolism. Finally, carbon flux was redirected more favorably towards the desired product, resulting in a boosted phloroglucinol titer of 1.30 g/L, increased by 2.04-fold. Overall, this study explored the use of a central byproduct-responsive biosensor system on improving cellular metabolic status, providing a general approach for enhancing bioproduction.

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设计一种溢出反应调节系统，以平衡细胞氧化还原作用并优化微生物生产

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来源期刊

Biotechnology and Bioengineering 工程技术-生物工程与应用微生物

CiteScore

7.90

自引率

5.30%

发文量

280

审稿时长

2.1 months

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