Abstract

Lincomycin, an antibiotic produced by Streptomyces lincolnensis , is widely used to treat Gram-positive bacterial and anaerobic infections. This study found that LmbU, a positive regulatory factor within the lincomycin biosynthesis gene cluster, can positively regulate the extracellular target gene cluster ectABCD ( ect ), which is involved in the synthesis of ectoine/hydroxyectoine. By knocking out ect , the lincomycin production was increased 2.8-fold. The addition of exogenous L -Asp in both xbl1 and Δ ect strains confirmed that the increased lincomycin production in Δ ect was due to enhanced precursor supply. Furthermore, osmotic stress experiments demonstrated that moderate NaCl concentrations could increase both ect expression and lincomycin production, while higher osmotic pressures resulted in decreased production and biomass. Together, these findings provide new mechanistic insights and offer a theoretical basis for the rational design of high-production industrial strains.