| Literature DB >> 31819261 |
Weishan Wang1,2, Shanshan Li3, Zilong Li4, Jingyu Zhang5, Keqiang Fan4, Gaoyi Tan5, Guomin Ai4, Sin Man Lam6, Guanghou Shui6, Zhiheng Yang5, Hongzhong Lu5, Pinjiao Jin3, Yihong Li4, Xiangyin Chen5, Xuekui Xia7, Xueting Liu5,8, H Kathleen Dannelly9, Chen Yang10, Yi Yang5, Siliang Zhang5, Gil Alterovitz11, Wensheng Xiang12, Lixin Zhang13.
Abstract
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 B1a in Streptomyces coelicolor, Streptomyces venezuelae, Streptomyces rimosus and Streptomyces avermitilis. Application of ddTAG increased the titer of avermectin B1a by 50% to 9.31 g l-1 in a 180-m3 industrial-scale fermentation, which is the highest titer ever reported. Our strategy could improve polyketide titers for pharmaceutical production.Entities:
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Year: 2019 PMID： 31819261 DOI： 10.1038/s41587-019-0335-4
Source DB: PubMed Journal: Nat Biotechnol ISSN： 1087-0156 Impact factor: 54.908