American Chemical Society
jf2c00285_si_002.xlsx (12.84 MB)

Promoting Butenyl-spinosyn Production Based on Omics Research and Metabolic Network Construction in Saccharopolyspora pogona

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posted on 2022-03-04, 19:06 authored by Jie Rang, Li Cao, Ling Shuai, Yang Liu, Zirong Zhu, Ziyuan Xia, Duo Jin, Yunjun Sun, Ziquan Yu, Shengbiao Hu, Qingji Xie, Liqiu Xia
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.