枯草芽孢杆菌底盘细胞的设计、构建与应用

doi:10.12211/2096-8280.2020-030

摘要/Abstract

摘要：

作为一种重要的模式工业微生物和食品安全微生物，枯草芽孢杆菌在工业酶和功能营养品的生产方面具有广泛应用。近年来，随着对枯草芽孢杆菌遗传调控机制的不断揭示，多种研究策略和技术，包括基因编辑系统、基因回路、空间支架、无细胞表达系统等，被用于设计和构建枯草芽孢杆菌底盘细胞高效合成各种生物化学品。本文首先对基于基因编辑和基于内源性调控系统的枯草芽孢杆菌底盘细胞设计与构建的策略进行了系统的概述。然后，以高产N-乙酰氨基葡萄糖、七烯甲萘醌、核黄素、透明质酸和β-环糊精糖基转移酶为例介绍了枯草芽孢杆菌底盘细胞工厂的应用。最后，从基因编辑效率提升、基因回路响应信号拓展和基因组设计与重构三方面对枯草芽孢杆菌底盘细胞的设计、构建与应用进行了展望。

关键词: 枯草芽孢杆菌, 底盘细胞, 基因组简化, 基因回路, 基因编辑

Abstract:

As a model industrial host and an important generally recognized as safe microorganism, Bacillus subtilis has been used for a wide range of applications such as the industrial production of enzymes and nutraceuticals. In recent years, with the elucidation of the genetic regulation mechanism of B. subtilis, various research strategies and technologies have been designed and developed with this chassis, including gene editing, gene circuits, spatial biomolecular scaffold and cell-free expression systems. In this review, we start with systematic summaries on the construction of B. subtilis chassis based on gene editing systems and endogenous regulatory mechanisms. Then applications of B. subtilis cell factories are discussed for producing N-acetylglucosamine, menaquinone-7, riboflavin, hyaluronic acid and β-cyclodextrin glycosyltransferase. Finally, prospects for the design, construction and applications of engineered B. subtilis strains are commented, with an emphasis on improving genome editing efficiency, expanding responsive metabolite spectrum for genetic circuits, and rewiring the whole genome.

Key words: Bacillus subtilis, chassis cell, reduced genome, gene circuit, gene editing

中图分类号:

Q819

林璐, 吕雪芹, 刘延峰, 堵国成, 陈坚, 刘龙. 枯草芽孢杆菌底盘细胞的设计、构建与应用[J]. 合成生物学, 2020, 1(2): 247-265.

Lu LIN, Xueqin LV, Yanfeng LIU, Guocheng DU, Jian CHEN, Long LIU. Advances in design, construction and applications of Bacillus subtilis chassis cells[J]. Synthetic Biology Journal, 2020, 1(2): 247-265.

图/表 20

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