A VioA Variant Activates Antibiotic Streptogramins in the Heterologous Host Streptomyces sp. OUC20-O

Heterologous expression of the G231L variant of VioA into 16 strains of marine-derived Streptomyces, combined with bioactivity tracking, leads to the activation of seven antibiotic streptogramins (1–7) in Streptomyces sp. OUC20-O. Among these, compound 1, named linstreptogramin, is a new compound with an unusual linear streptogramin skeleton. The planar structure and stereochemistry of compound 1 were established based on extensive MS and NMR spectroscopic analyses, together with ECD calculations. In the antibacterial activity evaluation, compounds 1–4 showed significant growth inhibition against the multidrug-resistant Enterococcus faecium CCARM 5203 with MIC values of 0.2–1.6 µg/mL, which are comparable to the positive control vancomycin.