微生物细胞工厂碳流调控进展

doi:10.16085/j.issn.1000-6613.2021-0680

摘要/Abstract

摘要：

随着代谢工程技术的进步，越来越多微生物细胞工厂可用于化学品发酵生产。微生物细胞生产化学品具有生产条件温和、环境友好等优势，是实现化学品绿色可持续生产的重要手段。为了提高微生物细胞工厂的产量、得率和生产强度，传统代谢工程手段主要采用基因过表达或基因敲除方式增大目标代谢路径碳代谢流。然而由于代谢流调控精度不足，易导致细胞生产能力下降。本文主要针对微生物细胞工厂碳流调控中存在的瓶颈问题，从代谢流改造靶点选择、细胞生长与产物合成碳流平衡、副产物路径与产物合成竞争、产物合成效率强化四个角度，系统综述微生物细胞工厂碳代谢流调控的最新进展。并从高精度、仿生学、智能化、多任务、快响应调控工具的设计出发，对未来微生物细胞工厂的发展趋势进行展望。

关键词: 微生物细胞工厂, 系统代谢工程, 合成生物学, 代谢流, 调控策略

Abstract:

With the development of metabolic engineering, many chemicals can be produced by microbial cell factories. Production of chemicals by microbial cell factories has the advantages of mild reaction conditions and environmental friendliness, and is an important way to realize sustainable production. To improve the chemicals titer, yield and productivity in microbial cell factories, traditional metabolic engineering methods mainly depend on gene overexpression or gene knockout methods to increase the metabolic flux towards the target metabolic pathway. However, due to the insufficient accuracy of metabolic flux regulation, it is easy to lead to the decline of cell production capacity. Aiming at solving the bottlenecks during carbon flux regulation in microbial cell factories, this review systematically summarizes the latest progress from four perspectives: target selection of metabolic flux regulation, carbon flux balance between cell growth and chemicals synthesis, competition between by-product pathway and product synthesis, and pathway efficiency enhancement in product synthesis. The future development trend of building microbial cell factory is also prospected from the design of high-accuracy, bionic, intelligent, multi-task and quick-response tools.

Key words: microbial cell factories, systematic metabolic engineering, synthetic biology, metabolic flux, regulatory strategy

中图分类号:

Q815

高聪, 郭亮, 胡贵鹏, 陈修来, 刘立明. 微生物细胞工厂碳流调控进展[J]. 化工进展, 2021, 40(12): 6807-6817.

GAO Cong, GUO Liang, HU Guipeng, CHEN Xiulai, LIU Liming. Advances of metabolic flux regulation in microbial cell factories[J]. Chemical Industry and Engineering Progress, 2021, 40(12): 6807-6817.

图/表 4

图1 如何解决菌体生长与目标产物合成竞争的问题

图2 如何解决副产物路径与目标产物合成竞争的问题

图3 解决目标产物合成路径效率低的问题

图4 未来代谢调控工具发展方向

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