文献类型：期刊文献

英文题名：A Self-Sustained System Spanning the Primary and Secondary Metabolism Stages to Boost the Productivity of Streptomyces

作者：Zhao, Ming[1];Wang, Mingrui[1];Wang, Shuiling[1];Xiong, Liangbin[1,2];Gao, Bei[1];Liu, Min[1];Tao, Xinyi[1];Wang, Feng-Qing[1];Wei, Dongzhi[1]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Newworld Inst Biotechnol, Shanghai 200237, Peoples R China;[2]Shanghai Univ Med & Hlth Sci, Shanghai Key Lab Mol Imaging, Shanghai 201318, Peoples R China

年份：2022

卷号：11

期号：1

起止页码：353

外文期刊名：ACS SYNTHETIC BIOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000736859100001)】；

基金：This work was financially supported by the National Natural Science Foundation of China (no. 21776075), the Chinese Postdoctoral Science Foundation (no. 2020M671021), and the Natural Science Foundation of Shanghai (no. 20ZR1415100).

语种：英文

外文关键词：Streptomyces; sigma(hrdB); PkasO* mutant; metabolic regulation

摘要：Streptomyces species possess strong secondary metabolism, the switches of which from the primary metabolism are complex and thus a challenge to holistically optimize their productivities. To avoid the complex switches and to reduce the limitations of different metabolic stages on the synthesis of metabolites, we designed a Streptomyces self-sustained system (StSS) that contains two functional modules, the primary metabolism module (PM) and the secondary metabolism module (SM). The PM includes endogenous housekeeping sigma factor sigma(hrdB) and sigma(hrdB)-dependent promoters, which are used to express target genes in the primary metabolism phase. SM consists of the expression cassette of sigma(hrdB) under the control of a secondary metabolism promoter, which maintains continuous activity of the sigma(hrdB)-dependent promoters in the secondary metabolism phase. As a proof-of-principle, the StSS was used to boost the production of some non-toxic metabolites, including indigoidine, undecylprodigiosin (UDP), ergothioneine, and avermectin, in Streptomyces. All these metabolites can undergo a continuous production process spanning the primary and secondary metabolism stages instead of being limited to a specific stage. Scale-up of UDP fermentation in a 4 L fermentor indicated that the StSS is a stable and robust system, the titer of which was enhanced to 1.1 g/L, the highest at present. This study demonstrated that the StSS is a simple but powerful strategy to rationally engineer Streptomyces cell factories for the efficient production of non-toxic metabolites via reconstructing the relationships between primary and secondary metabolism.