Improvement of Daptomycin Production in Streptomyces roseosporus through the Acquisition of Pleuromutilin Resistance

Abstract EN

Daptomycin, a cyclic lipopeptide antibiotic produced by Streptomyces roseosporus, displays potent activity against a variety of gram-positive pathogens.

There is a demand for generating high-producing strains for industrial production of this valuable antibiotic.

Ribosome engineering is a powerful strategy to enhance the yield of secondary metabolites.

In this study, the effect of a diterpenoid antibiotic pleuromutilin resistance mutation on daptomycin production was assessed.

Spontaneous pleuromutilin-resistant derivatives of S.

roseosporus were isolated.

Sequencing of rplC locus (encoding the ribosomal protein L3) showed a point mutation at nt 455, resulting in the substitution of glycine with valine.

G152V mutants showed increased production of daptomycin by approximately 30% in comparison with the wild-type strain.

Its effect on daptomycin production was due to enhanced gene transcription of the daptomycin biosynthetic genes.

In conclusion, pleuromutilin could be used as a novel ribosome engineering agent to improve the production of desired secondary metabolites.