Up-regulated spinosad pathway coupling with the increased concentration of acetyl-CoA and malonyl-CoA contributed to the increase of spinosad in the presence of exogenous fatty acid

Abstract

Polyketides are important compounds with a staggering range of biological and medicinal activities. Previous studies have demonstrated that the addition of fatty acids can increase polyketides production. However, a detailed metabolic explanation of this phenomenon has not been established. The aim of this study was to explain the positive effect of exogenous fatty acids on polyketides production. Spinosyns are polyketide-derived macrolides. In our study, spinosyns were used, as an example, to study the positive effect of exogenous fatty acids on their production. In the presence of exogenous fatty acids, gene expression assays indicated that the transcription of de novo fatty acid biosynthesis was significantly decreased and the transcriptions of β-oxidation and spinosad biosynthesis were up-regulated. The decreased de novo fatty acid synthesis transcription and the increased β-oxidation transcription resulted in the increase of acetyl-CoA and malonyl-CoA. It is the up-regulated spinosad pathway coupling with the enhanced concentration of acetyl-CoA and malonyl-CoA that contributed to the increase of spinosad. Taken together, a metabolic link among de novo fatty acid synthesis, β-oxidation, and spinosad biosynthesis at the presence of exogenous fatty acids was established. The results presented here enable researchers to better understand why added fatty acids can increase polyketides production.