Fermentation Optimization and Transcriptomic Analysis of Vancomycin Production in Amycolatopsis orientalis

Vancomycin is the drug of last resort against Staphylococcus aureus infections, yet its industrial production is constrained by the inherently low yields of wild-type strains. Through systematic optimization of culture medium and fermentation conditions, we increased vancomycin production by Amycolatopsis orientalis ATCC 19795 from 0.60 g/L to 2.28 g/L, a 3.8-fold improvement. Transcriptomic analysis revealed that this optimized process activated central carbon metabolism, precursor biosynthetic pathways, and the rpm ribosomal gene cluster, thereby enhancing both precursor availability and translational efficiency. Furthermore, the downregulation of genes involved in fatty acid and biotin synthesis redirected carbon flux toward central metabolism and the TCA cycle. This synergistic regulatory network drove a substantial increase in vancomycin production and provides a theoretical foundation for the rational metabolic engineering of industrial production strains.