Identification by gene deletion analysis of a regulator, VmsR, that controls virginiamycin biosynthesis in Streptomyces virginiae

Virginiae butanolide (VB)-BarA of Streptomyces virginiae is one of the newl y discovered pairs of a butyrolactone autoregulator and a corresponding rec eptor protein of Streptomyces species and regulates the production of the a ntibiotic virginiamycin (VM) in S. virginiae. The gene vmsR was found to be situated 4.7 kbp upstream of the barA gene, which encodes the VB-specific receptor. The vmsR product was predicted to be a regulator of VM biosynthes is based on its high homology to some Streptomyces pathway-specific transcr iptional regulators for the biosynthetic gene clusters of polyketide antibi otics, such as Streptomyces peucetius DnrI (47.5% identity, 84.3% similarit y), which controls daunorubicin biosynthesis. A vmsR deletion mutant was cr eated by homologous recombination. Neither virginiamycin M-1 nor virginiamy cin S was produced in the vmsR mutant, while amounts of VB and BarA similar to those produced in the wild-type strain were detected. Reverse transcrip tion-PCR analyses confirmed that the vmsR deletion had no deleterious effec ts on the transcription of the vmsR-surrounding genes, indicating that VmsR is a positive regulator of VM biosynthesis in S. virginiae.