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Understanding the metabolism of Saccharopolyspora pogona on a global scale is essential for manipulating its metabolic capabilities to improve butenyl-spinosyn biosynthesis. Here, we combined multiomics analysis to parse S. pogona genomic information, construct a metabolic network, and mine important functional genes that affect the butenyl-spinosyn biosynthesis. This research not only elucidated the relationship between butenyl-spinosyn biosynthesis and the primary metabolic pathway but also showed that the low expression level and continuous downregulation of the bus cluster and the competitive utilization of acetyl-CoA were the main reasons for reduced butenyl-spinosyn production. Our framework identified 148 genes related to butenyl-spinosyn biosynthesis that were significantly differentially expressed, confirming that butenyl-spinosyn polyketide synthase (PKS) and succinic semialdehyde dehydrogenase (GabD) play an important role in regulating butenyl-spinosyn biosynthesis. Combined modification of these genes increased overall butenyl-spinosyn production by 6.38-fold to 154.1 ± 10.98 mg/L. Our results provide an important strategy for further promoting the butenyl-spinosyn titer.

Citation

Jie Rang, Li Cao, Ling Shuai, Yang Liu, Zirong Zhu, Ziyuan Xia, Duo Jin, Yunjun Sun, Ziquan Yu, Shengbiao Hu, Qingji Xie, Liqiu Xia. Promoting Butenyl-spinosyn Production Based on Omics Research and Metabolic Network Construction in Saccharopolyspora pogona. Journal of agricultural and food chemistry. 2022 Mar 23;70(11):3557-3567

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PMID: 35245059

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