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

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.