posted on 2022-03-04, 19:06authored byJie 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.