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Enhanced production of virginiamycin with the maintained optimal ratio of its components by a mutant Streptomyces virginiae IB 25–8 strain

Savushkin, Vyacheslav A., Dzhavakhiya, Vakhtang V., Glagoleva, Elena V., Savelyeva, Veronika V., Voskresenskaya, Evgeniya D., Ovchinnikov, Alexander I., Glagolev, Vladislav I., Novak, Nikita V., Grebeneva, Yana O.
Biocatalysis and agricultural biotechnology 2019 v.17 pp. 408-415
Streptomyces virginiae, biosynthesis, fermentation, genes, mutagenesis, mutants, veterinary drugs, virginiamycin
Virginiamycin, a widely used veterinary antibiotic produced by Streptomyces virginiae, represents a natural mix of two macrocyclic peptidolactones; its main components are the M1 and S1 factors, which act synergistically when present in the optimum ratio of 75:25. Because of a large number of genes involved into the virginiamycin biosynthesis, the development of high-yield strains able to synthesize M1 and S1 at a synergistic ratio with the total productivity exceeding 4 g/L still remains a relevant problem. Using a multi-step random UV mutagenesis with the simultaneous control of the M1:S1 ratio in a final product, a new highly productive and genetically stable S. virginiae strain IB 25–8 was obtained. After the medium improvement combined with the addition of a Diaion™ HP21 resin absorbing up to 98.5% of the total virginiamycin, the productivity of the strain has reached 5.21 ± 0.16 g/L, while the M1:S1 ratio remained to be synergistic (75:25). The effect of various medium components, their concentration, and resin types on the M1:S1 ratio has been shown. The obtained strain is promising for the industrial use due to its high productivity and the optimal M1:S1 ratio. A pre-fermentation addition of the selected DIAION™ HP21 resin to fermentation medium increases the total yield and simplifies the further isolation and purification of virginiamycin.