Impact of the GouM transporter on secondary metabolism activation and production yield in Streptomyces noursei strain CK‐15

Abstract

Streptomyces noursei produces various bioactive secondary metabolites with agricultural significance; however, the regulatory mechanisms governing their production and secretion remain largely unexplored. To address this, we systematically characterized the secondary metabolic potential of S . noursei CK‐15 and investigated the role of the transporter gene gouM in regulating gougerotin efflux and global cluster interactions. PacBio sequencing revealed a 9.34 Mb linear genome containing 36 biosynthetic gene clusters. Through genetic manipulation and transcriptomic analysis, we demonstrated that overexpression of the cluster‐situated transporter gouM significantly enhanced gougerotin secretion, boosting the total yield to 1.97 g/L, which represents a 114% increase over the wild‐type strain. Conversely, gouM deletion disrupted central carbon metabolism and resulted in reduced gougerotin production. Notably, transcriptomic profiling revealed extensive cross‐regulation among BGCs: targeted engineering of the gougerotin cluster not only altered its own transcription but also differentially modulated known clusters and successfully activated multiple silent or cryptic pathways, including those involved in siderophore, streptothricin, and bosamycin biosynthesis. These findings establish a direct link between transporter gene activity and both metabolite efflux and silent‐cluster awakening, providing a novel engineering strategy for titer improvement and natural product discovery in Streptomyces species.