Involvement of SgvP in Carbon-Sulfur Bond Formation during Griseoviridin Biosynthesis

Griseoviridin (GV) is an A-type streptogramin antibiotic displaying antimicrobial activity and acting synergistically with viridogrisein (VG). Bioinformatic analyses reveal SgvP as the sole cytochrome P450 enzyme in the GV/VG gene cluster. To explore the role of SgvP in the GV/VG pathway, we inactivated the sgvP gene. The resulting sgvP mutant generated two new products: GV-1 and GV-2, both lacking the CS bridge. In trans complementation of the sgvP gene into the sgvP mutant strain partially restores GV production. Feeding [1-13C]-labeled cysteine to the wild-type strain led to enrichment of C-7 in the GV scaffold, thus verifying that the CS bond in GV is formed through direct coupling of the free SH group provided by the side chain of cysteine. The above results highlight the significance of SgvP in CS bond formation in griseoviridin biosynthesis.