Effects of Mannitol on the Growth, Metabolism, and Butenyl-Spinosyn Biosynthesis of <i>Saccharopolyspora pogona</i>

The metabolic pathways of high-yielding strains developed through physical and chemical mutagenesis can be modified, particularly those involved in carbon metabolism. The distribution of nutrients in the fermentation medium is likely to be a key bottleneck in further improving yields. In this study, we screened different carbon sources for the high-yield Saccharopolyspora pogona ASAGF19 strain and investigated the underlying mechanisms. The results demonstrated that mannitol was the optimal carbon source, increasing biomass and butenyl-spinosyn production by 1.58- and 1.88-fold, respectively, compared to glucose. The specific growth rate and carbon source utilization efficiency in the mannitol group were 7.37- and 1.68-fold higher than in the glucose group at 96 h of fermentation. Additionally, at 72 h, the synthesis rate of butenyl-spinosyn and the carbon yield in the mannitol group increased by 2.02- and 1.89-fold, respectively. Mannitol also enhanced the transcription of genes involved in the biosynthesis of butenyl-spinosyn, elevated NADPH levels during the early stage of fermentation, and maintained cellular redox homeostasis. Its supplementation in the fermentation medium also promoted butenyl-spinosyn biosynthesis. The increased nicotinamide adenine dinucleotide phosphate supply in the early stage, along with maintained intracellular redox balance, likely contributed to the highly efficient biosynthesis of butenyl-spinosyn in S. pogona ASAGF19. This study is the first to investigate the mechanism by which mannitol enhances butenyl-spinosyn production.