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.

Therapeutic effects of lincomycin and level of drug degradation in broiler tissues after treatment

“…Lincomycin exhibits good bactericidal activity against Gram-positive bacteria by inhibiting protein synthesis [ 31 ]. Lincomycin is often combined with other antimicrobials, such as kitasamycin [ 32 ], spectinomycin [ 4 , 32 , 33 ], diclazuril [ 14 ], and bacitracin [ 15 ], to enhance its effectiveness.…”

Coupled strategy based on regulator manipulation and medium optimization empowers the biosynthetic overproduction of lincomycin

“…Fermentation broth (10 mL) was used as the sample, which was removed using centrifugation (4000× g , 10 min), and the packed mycelium volume (PMV) was considered the percentage of the precipitate volume in 10 mL of fermentation broth [ 24 ]. The Fehling method was used to measure reducing sugar concentrations [ 23 ], and the supernatants of the samples were analyzed for nitrogen levels via formaldehyde titration [ 10 ].…”

“…Lincomycin A (Lin-A), comprising an α-methylthiolincosamide and N-methylated 4-propyl- l -proline, is a major fermentation product of the actinomycete Streptomyces lincolnensis [ 22 ]. Owing to the global market of hundreds of tons per year, improving the yield of lincomycin is of significance [ 23 ]. Random mutagenesis and fermentation optimization have been frequently used to increase lincomycin production [ 24 , 25 ], and considerable efforts have been recently devoted to understand lincomycin biosynthesis and its regulation [ 22 , [26] , [27] , [28] , [29] ].…”

Pharmacological Studies on Lincomycin in Broilers with Necrotic Enteritis (Cl. Perfringens)

“…Its range of action against Gram-positive bacteria and most anaerobes depends on the medication's concentration at the disease site and the response of the contaminated living being. [8].…”