Engineered Coenzyme A Biosynthesis and Butyrate Transporter Drives High‐Efficient Butyrate Synthesis in Escherichia coli

IF 3.6 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology and Bioengineering Pub Date : 2025-07-11 DOI:10.1002/bit.70018

Jinhui Li, Yi Xing, Xin Wang, Tong Zhu, Feiyu Fan, Hongtao Xu, Peipei Han, Jun Cai, Xinna Zhu, Xueli Zhang

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引用次数: 0

Abstract

Butyric acid is a four‐carbon fatty acid with a range of applications in chemical, food and pharmaceutical industries. In this study, a heterologous butyrate biosynthetic pathway was engineered in Escherichia coli, which was afflicted by low titer and low yield. To address these issues, two key strategies for metabolic engineering of E. coli were implemented by enhancing coenzyme A (CoA) biosynthesis and optimizing butyrate transport. First, the CoA biosynthesis pathway was engineered through alleviating CoA‐mediated inhibition, and enhancing the supply of pantothenate and cysteine precursors. Second, a TolC‐associated MdtEF efflux pumps was identified and optimized to mitigate butyrate reuptake. The combined implementation in strain JH016 led to 11.1‐fold and 86% increase of butyrate titer and yield, resulting in production of 21.12 g/L butyrate with a yield of 0.95 mol/mol. Our results suggested that CoA engineering and butyrate transporter optimization had a synergistic effect on butyrate production. Furthermore, these strategies could be broadly utilized for the production of various other useful chemicals in the fields of metabolic engineering and synthetic biology.

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工程辅酶A生物合成和丁酸转运蛋白驱动大肠杆菌高效合成丁酸盐

丁酸是一种四碳脂肪酸，在化工、食品和制药工业中有着广泛的应用。本研究在大肠杆菌中构建了一种低效价、低产率的异源丁酸酯生物合成途径。为了解决这些问题，本研究通过加强辅酶A （CoA）的生物合成和优化丁酸盐的转运来实现大肠杆菌代谢工程的两个关键策略。首先，通过减轻CoA介导的抑制，增强泛酸和半胱氨酸前体的供应，设计了CoA生物合成途径。其次，确定并优化了与TolC相关的MdtEF外排泵，以减轻丁酸再摄取。在菌株JH016上联合实施，丁酸滴度和产率分别提高了11.1倍和86%，产率为21.12 g/L，产率为0.95 mol/mol。结果表明，CoA工程和丁酸转运体优化对丁酸酯的合成具有协同效应。此外，这些策略可广泛用于代谢工程和合成生物学领域的各种其他有用化学品的生产。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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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