Abstract

Synthetic biology provides powerful tools and novel strategies for designing and modifying microorganisms to function as cell factories for biomanufacturing, which is a promising approach for realizing chemical production in a green and sustainable manner. Recent advances in genetic component design and genome engineering have enabled significant progresses in the field of synthetic biology chassis that have been developed for enzymes or biochemical production based on synthetic biology strategies, with particular reference to model microorganisms, such as Escherichia coli, Bacillus subtilis, Corynebacterium glutamicum, and Saccharomyces cerevisiae. In this review, strategies for engineering four different functional cellular modules which encompass the total process of biomanufacturing are discussed, including expanding the substrate spectrum for substrate uptake modules, refactoring biosynthetic pathways and dynamic regulation for product synthesis modules, balancing energy and redox modules, and cell membrane and cell wall engineering of product storage and secretion modules. Novel strategies of integrating and coordinating different cellular modules aided by synthetic co-culturing of multiple chassis, artificial intelligence–aided data mining for guiding strain development, and the process for designing automatic chassis development via biofoundry are expected to generate next generations of model microorganism chassis for more efficient biomanufacturing.

Key points

• Engineering of functional cellular modules facilitate next generations of chassis construction.

• Global optimization of biosynthesis can be improved by metabolic models.

• Data-driven and automatic strain development can improve microorganism chassis construction.

中文翻译：

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面向用于生物制造的下一代模型微生物底盘。

摘要

合成生物学为设计和修饰微生物以用作生物制造的细胞工厂提供了强大的工具和新颖的策略，这是一种以绿色和可持续方式实现化学生产的有前途的方法。遗传成分设计和基因组工程的最新进展已使合成生物学底盘领域取得了重大进展，该领域已基于合成生物学策略，特别是针对模型微生物，例如大肠杆菌，枯草芽孢杆菌，谷氨酸棒杆菌和酿酒酵母。在这篇综述中，讨论了工程化四个不同功能性细胞模块的策略，这些模块涵盖了生物制造的整个过程，包括扩大底物吸收模块的底物谱，重构生物合成途径和产品合成模块的动态调节，平衡能量和氧化还原模块以及细胞膜和细胞壁工程的产品存储和分泌模块。有望通过多种底盘的合成共培养，通过人工智能辅助的数据挖掘指导菌株开发以及通过生物铸造设计自动底盘开发过程的新策略，整合和协调不同细胞模块，从而产生下一代模型微生物底盘用于更有效的生物制造。

关键点

•功能性蜂窝模块的工程设计有助于下一代机箱的构建。

•代谢模型可以改善生物合成的整体优化。

•数据驱动和自动菌株开发可以改善微生物底盘的构建。