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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

Author:
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.
Source:
Biocatalysis and agricultural biotechnology 2019 v.17 pp. 408-415
ISSN:
1878-8181
Subject:
Streptomyces virginiae, biosynthesis, fermentation, genes, mutagenesis, mutants, veterinary drugs, virginiamycin
Abstract:
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.
Agid:
6266784