Ma Xiaoyan, Ma Lianjie, Huo Yi-Xin
Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, 5 South Zhongguancun Street, Haidian District, Beijing 100081, People's Republic of China.
Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, 5 South Zhongguancun Street, Haidian District, Beijing 100081, People's Republic of China; Tobacco Research Institute, Chinese Academy of Agricultural Sciences, Qingdao 266101, People's Republic of China.
Trends Biotechnol. 2022 Jun;40(6):735-751. doi: 10.1016/j.tibtech.2021.11.002. Epub 2021 Dec 9.
An ideal microbial cell factory (MCF) should deliver maximal resources to production, which conflicts with the microbe's native growth-oriented resource allocation strategy and can therefore lead to early termination of the high-yield period. Reallocating resources from growth to production has become a critical factor in constructing robust MCFs. Instead of strengthening specific biosynthetic pathways, emerging endeavors are focused on rearranging the gene regulatory network to fundamentally reprogram the resource allocation pattern. Combining this idea with transcriptional regulation within the hierarchical regulatory network, this review discusses recent engineering strategies targeting the transcription machinery, module networks, regulatory edges, and bottom network layer. This global view will help to construct a production-oriented phenotype that fully harnesses the potential of MCFs.
理想的微生物细胞工厂（MCF）应将最大资源用于生产，这与微生物以生长为导向的天然资源分配策略相冲突，因此可能导致高产期提前终止。将资源从生长重新分配到生产已成为构建稳健MCF的关键因素。新兴的努力不是强化特定的生物合成途径，而是专注于重新排列基因调控网络，从根本上重新编程资源分配模式。将这一理念与层次调控网络中的转录调控相结合，本综述讨论了针对转录机制、模块网络、调控边缘和底层网络层的近期工程策略。这种全局观点将有助于构建一种以生产为导向的表型，充分发挥MCF的潜力。
