谷氨酸棒杆菌耐受胁迫机制及工业鲁棒性合成生物学研究进展

Advances in stress tolerance mechanisms and synthetic biology for the industrial robustness of Corynebacterium glutamicum

摘要:

谷氨酸棒杆菌Corynebacterium glutamicum作为一般被认为具有生物安全性的一种模式工业微生物，不仅在发酵工业中成功用于大规模生产氨基酸，而且具有合成多种新型化学品的潜力。谷氨酸棒杆菌菌株在生产化合物时，经常会受到各种逆境条件的胁迫，从而降低细胞活力和生产性能。合成生物学的发展为提高谷氨酸棒杆菌的鲁棒性提供了新的技术手段。本文总结了谷氨酸棒杆菌应对发酵过程中各种胁迫的耐受机制。同时，重点介绍提高谷氨酸棒杆菌底盘细胞鲁棒性和耐受性的合成生物学新策略，包括挖掘新的抗逆元件、改造转录调控因子、利用适应性进化策略挖掘抗逆功能模块等。最后，从生物传感器、转录调控因子的筛选和设计、多种调控元件利用等方面对提高谷氨酸棒杆菌底盘细胞鲁棒性进行了展望。

Abstract:

As a model industrial host and microorganism with the generally regarded as safe (GRAS) status, Corynebacterium glutamicum not only produces amino acids on a large scale in the fermentation industry, but also has the potential to produce various new products. C. glutamicum usually encounters various stresses in the process of producing compounds, which severely affect cell viability and production performance. The development of synthetic biology provides new technical means for improving the robustness of C. glutamicum. In this review, we discuss the tolerance mechanisms of C. glutamicum to various stresses in the fermentation process. At the same time, we highlight new synthetic biology strategies for boosting C. glutamicum robustness, including discovering new stress-resistant elements, modifying transcription factors, and using adaptive evolution strategies to mine stress-resistant functional modules. Finally, prospects of improving the robustness of engineered C. glutamicum strains ware provided, with an emphasis on biosensor, screening and design of transcription factors, and utilizing the multiple regulatory elements.