Simultaneous improvement of lincomycin A production and reduction of lincomycin B levels in Streptomyces lincolnensis using a combined medium optimization approach

Abstract

Purpose: The current study aimed to optimize the culture and production parameters of industrial production of lincomycin A by Streptomyces lincolnensis using a statistical approach that could also reduce unwanted by-products. Methods: The Plackett-Burman design, steepest ascent method, and response surface design were used to evaluate different factors that affect lincomycin A production. Results: Using an optimized S. lincolnensis fermentation medium, lincomycin A production was increased up to 4600 mg/L in shaking flasks, which indicated a 28.3% improvement over previous production in an un-optimized medium (3585 mg/L). Additionally, the concentration of lincomycin B by-product was reduced to 0.8%, which was 82.2% lower than that in the un-optimized medium. Further, quantitative real-time PCR analysis revealed the optimized medium improved lincomycin A production by stimulating key genes in the lincomycin A biosynthesis pathway, as well as an osmotic stress gene. Conclusions: Based on the results, the sequential optimization strategy in this study provides powerful means for the enhancement of lincomycin A with less by-product. We found that osmotic stress reduced the concentration of lincomycin B, which could also help reduce fermentation by-product yields in other actinobacteria.