Abstract: The production of bulk chemicals and natural products from renewable feedstocks by microbial cell factories is promising and sustainable. Tailoring natural or synthetic pathways in microbial hosts provide a foundation for constructing microbial cell factories. However, tailoring natural or synthetic pathways in microbial hosts always cause metabolic disturbance, which would reduce the suitability as well as the performance of microbial cell factories. The performance of microbial cell factories could be enhanced by reinforcing suitability between different metabolic pathways or by improving suitability between metabolic pathways and microbial cells. In this review, we discussed recent studies about reinforcing and balancing the metabolic flux of synthetic pathway, limiting cross-talk between the engineered pathways and the cellular milieu, and improving the suitability of metabolic pathway and microbial cell, which provided an opportunity to enhance the performance of microbial cell factories. Furthermore, future research directions to develop multidimensional regulation strategy for reprogramming the suitability of metabolic pathways at the cellular level and enhancing the suitability of microbial cells to metabolite.

Key words: microbial cell factories, suitability, systems metabolic engineering, synthetic biology, regulatory strategy

摘要： 微生物细胞工厂以可再生资源为原料，实现了大宗化学品和天然产物的可持续生产，并有望替代石油化工炼制和动植物提取。剪接天然或人工代谢路径是构建微生物细胞工厂的基础。然而，剪接代谢路径造成的代谢流扰动，导致微生物细胞工厂的适配性差，降低了微生物细胞工厂的生产性能。提高人工代谢路径之间的适配性，以及人工代谢路径与底盘微生物细胞之间的适配性，将是改善微生物细胞工厂生产性能的关键。本文从强化与平衡人工代谢路径的代谢通量，解除人工代谢路径与底盘细胞内源代谢路径的交互作用，以及强化人工代谢路径与底盘细胞整体代谢网络的适配性层面，对提高微生物细胞工厂适配性的研究现状进行介绍。开发高效的多重适配性调控策略，在细胞水平重置代谢路径的适配性与提高微生物细胞对代谢产物的适配性，将是未来的研究重点。

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