文献类型：期刊文献

英文题名：Harnessing the intracellular triacylglycerols for titer improvement of polyketides in Streptomyces

作者：Wang, Weishan[1,2];Li, Shanshan[3];Li, Zilong[1];Zhang, Jingyu[2];Fan, Keqiang[1];Tan, Gaoyi[2];Ai, Guomin[1];Lam, Sin Man[4];Shui, Guanghou[4];Yang, Zhiheng[2];Lu, Hongzhong[2];Jin, Pinjiao[3];Li, Yihong[1];Chen, Xiangyin[2];Xia, Xuekui[5];Liu, Xueting[2,6];Dannelly, H. Kathleen[7];Yang, Chen[8];Yang, Yi[2];Zhang, Siliang[2];Alterovitz, Gil[9];Xiang, Wensheng[3];Zhang, Lixin[2]

机构：[1]Chinese Acad Sci, Inst Microbiol, State Key Lab Microbial Resources, Beijing, Peoples R China;[2]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai, Peoples R China;[3]Chinese Acad Agr Sci, Inst Plant Protect, State Key Lab Biol Plant Dis & Insect Pests, Beijing, Peoples R China;[4]Chinese Acad Sci, Inst Genet & Dev Biol, State Key Lab Mol Dev Biol, Beijing, Peoples R China;[5]Qilu Univ Technol, Shandong Acad Sci, Key Biosensor Lab Shandong Prov, Inst Biol, Jinan, Peoples R China;[6]Qingdao Natl Lab Marine Sci & Technol, Lab Marine Biol & Biotechnol, Qingdao, Peoples R China;[7]Indiana State Univ, Terre Haute, IN 47809 USA;[8]Chinese Acad Sci, Shanghai Inst Plant Physiol & Ecol, CAS Ctr Excellence Mol Plant Sci, CAS Key Lab Synthet Biol, Shanghai, Peoples R China;[9]Boston Childrens Hosp, Boston, MA USA

年份：2020

卷号：38

期号：1

起止页码：76

外文期刊名：NATURE BIOTECHNOLOGY

收录：;EI(收录号：20195107877987);WOS:【SCI-EXPANDED(收录号:WOS:000510337700016)】；

语种：英文

外文关键词：Ketones - Metabolism - Biochemistry - Bacteria - Metabolites - Glycerol

摘要：Polyketide yields in Streptomyces are boosted by routing stored intracellular triacylglycerol into pathways that make industrially relevant products. Pharmaceutically important polyketides such as avermectin are mainly produced as secondary metabolites during the stationary phase of growth of Streptomyces species in fermenters. The source of intracellular metabolites that are funneled into polyketide biosynthesis has proven elusive. We applied multi-omics to reveal that intracellular triacylglycerols (TAGs), which accumulates in primary metabolism, are degraded during stationary phase. This process could channel carbon flux from both intracellular TAGs and extracellular substrates into polyketide biosynthesis. We devised a strategy named 'dynamic degradation of TAG' (ddTAG) to mobilize the TAG pool and increase polyketide biosynthesis. Using ddTAG we increased the titers of actinorhodin, jadomycin B, oxytetracycline and avermectin B-1a in Streptomyces coelicolor, Streptomyces venezuelae, Streptomyces rimosus and Streptomyces avermitilis. Application of ddTAG increased the titer of avermectin B-1a by 50% to 9.31 g l(-1) in a 180-m(3) industrial-scale fermentation, which is the highest titer ever reported. Our strategy could improve polyketide titers for pharmaceutical production.