The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800, Kongens Lyngby, Denmark.
Biotechnol J. 2019 Sep;14(9):e1800439. doi: 10.1002/biot.201800439. Epub 2019 Jun 12.
The bio-based production of added-value compounds (with applications as pharmaceuticals, biofuels, food ingredients, and building blocks) using bacterial platforms is a well-established industrial activity. The design and construction of microbial cell factories (MCFs) with robust and stable industrially relevant phenotypes, however, remains one of the biggest challenges of contemporary biotechnology. In this review, traditional and cutting-edge approaches for optimizing the performance of MCFs for industrial bioprocesses, rooted on the engineering principle of natural evolution (i.e., genetic variation and selection), are discussed. State-of-the-art techniques to manipulate and increase genetic variation in bacterial populations and to construct combinatorial libraries of strains, both globally (i.e., genome level) and locally (i.e., individual genes or pathways, and entire sections and gene clusters of the bacterial genome) are presented. Cutting-edge screening and selection technologies applied to isolate MCFs displaying enhanced phenotypes are likewise discussed. The review article is closed by presenting future trends in the design and construction of a new generation of MCFs that will contribute to the long-sought-after transformation from a petrochemical industry to a veritable sustainable bio-based industry.
利用细菌平台生产附加值化合物（应用于制药、生物燃料、食品成分和建筑模块）的生物生产是一项成熟的工业活动。然而，设计和构建具有稳健和稳定的工业相关表型的微生物细胞工厂（MCF）仍然是当代生物技术面临的最大挑战之一。在这篇综述中，讨论了基于自然进化工程原理（即遗传变异和选择）优化 MCF 用于工业生物过程性能的传统和前沿方法。介绍了用于在细菌种群中操纵和增加遗传变异以及构建菌株组合文库的最先进技术，包括全局（即基因组水平）和局部（即单个基因或途径以及细菌基因组的整个部分和基因簇）。同样讨论了应用于分离显示增强表型的 MCF 的前沿筛选和选择技术。本文通过介绍新一代 MCF 的设计和构建的未来趋势，为从石化工业向真正可持续的生物基工业的长期追求转变做出了贡献。
