期刊
ACS SYNTHETIC BIOLOGY
卷 11, 期 11, 页码 3772-3784出版社
AMER CHEMICAL SOC
DOI: 10.1021/acssynbio.2c003623772
关键词
marine microorganism; heterologous expression; chassis cell; transcriptome
资金
- National Natural Science Foundation of China [82022067, 22037006, 31870046]
- Key Special Project for Introduced Talents Team of Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou) [GML2019ZD0406]
- Local Innovation and Entrepreneurship Team Project of Guangdong [2019BT02Y262]
- Open Program of Shen Zhen Bay Laboratory [SZBL2021080601006]
- Key Science and Tech- nology project of Hainan Province [ZDKJ202018]
- Rising Star Foundation of the South China Sea Institute of Oceanology [NHXX2019SW0101]
Marine microorganisms produce bioactive secondary metabolites, which are important for discovering novel antibiotics. We have built an efficient marine-derived gene clusters expression platform by engineering Streptomyces atratus. This platform allows for the expression of microbial secondary metabolites, especially those of marine origin.
Marine microorganisms produce a variety of bioactive secondary metabolites, which represent a significant source of novel antibiotics. Heterologous expression is a valuable tool for discovering marine microbial secondary metabolites; however, marine-derived chassis cell is very scarce. Here, we build an efficient plug-and-play marine-derived gene clusters expression platform 1.0 (MGCEP 1.0) by the systematic engineering of the deep-sea-derived Streptomyces atratus SCSIO ZH16. For a proof of concept, four families of microbial bioactive metabolite biosynthetic gene clusters (BGCs), including alkaloids, aminonucleosides, nonribosomal peptides, and polyketides, were efficiently expressed in this platform. Moreover, 19 compounds, including two new angucycline antibiotics, were produced in MGCEP 1.0. Dynamic patterns of global biosynthetic gene expression in MGCEP 1.0 with or without a heterologous gene cluster were revealed at the transcriptome level. The platform MGCEP 1.0 provides new possibilities for expressing microbial secondary metabolites, especially of marine origin.
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