合成生物学时代基于非模式细菌的工业底盘细胞研究现状与展望

Progress and perspective on development of non-model industrial bacteria as chassis cells for biochemical production in the synthetic biology era

摘要:

工业微生物底盘细胞的开发将为工业生物技术的发展提供优良的细胞工厂，有利于实现环境保护及经济可持续发展。基于合成生物学“设计-构建-测试-学习” (Design-Build-Test-Learn，DBTL) 策略，对底盘细胞进行多维度的理性或半理性改造是实现“建物致知”以及“建物致用”目标的重要手段。文中简述了合成生物学DBTL策略中各步骤相关的重要技术方法；概述了部分重要模式微生物底盘细胞的策略与研究进展；重点比较介绍了工业生物技术领域具有特殊生理功能、利用一碳化合物及高效生产平台化合物的部分非模式细菌；同时也提出了实现优良、安全合成微生物细胞工厂构建与应用的策略。这些方法策略包括依靠合成生物学技术方法，综合模式与非模式微生物优势，开发应用经济、高效的高通量智能装备，建立分子组学与表型组学研究平台，推动多层次系统生物学与表型组学大数据的解析、整合、模拟与可视化，以及建立高质量的数字细胞模型和基因组优化的底盘细胞，推动高效、优良工业细胞工厂的理性设计、构建与应用。

Abstract:

The development and implement of microbial chassis cells can provide excellent cell factories for diverse industrial applications, which help achieve the goal of environmental protection and sustainable bioeconomy. The synthetic biology strategy of Design-Build-Test-Learn (DBTL) plays a crucial role on rational and/or semi-rational construction or modification of chassis cells to achieve the goals of “Building to Understand” and “Building for Applications”. In this review, we briefly comment on the technical development of the DBTL cycle and the research progress of a few model microorganisms. We mainly focuse on non-model bacterial cell factories with potential industrial applications, which possess unique physiological and biochemical characteristics, capabilities of utilizing one-carbon compounds or of producing platform compounds efficiently. We also propose strategies for the efficient and effective construction and application of synthetic microbial cell factories securely in the synthetic biology era, which are to discover and integrate the advantages of model and non-model industrial microorganisms, to develop and deploy intelligent automated equipment for cost-effective high-throughput screening and characterization of chassis cells as well as big-data platforms for storing, retrieving, analyzing, simulating, integrating, and visualizing omics datasets at both molecular and phenotypic levels, so that we can build both high-quality digital cell models and optimized chassis cells to guide the rational design and construction of microbial cell factories for diverse industrial applications.