DSpace at VNU: Deciphering On-Off signalling network of Streptomyces secondary metabolism

Deciphering On-Off signalling network of Streptomyces secondary metabolism Takuya Nihira* International Center for Biotechnology, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan ABSTRACT Virginiamycin M (VM) of Streptomyces virginiae is a hybrid peptide-polyketide antibiotic with peptide antibiotic virginiamycin S (VS) as its synergistic counterpart VM and VS belong to the Streptogramin family, which is characterized by strong synergistic antibacterial activity, and their water-soluble derivatives are a new therapeutic option for combating vancomycin-resistant Gram-positive bacteria The production of virginiamycin is under the tight control of microbial hormone, called Virginiae Butanolide (VB) of the -butyrolactone autoregulator group, and the VB-specific receptor protein (BarA) The VM biosynthetic gene cluster was isolated from S virginiae in the 77-kb region including about 10-kb of the regulatory island for virginiamycin production Sequence analysis revealed that the region consists of 41 complete open reading frames (ORFs), encoding hybrid nonribosomal peptide synthetase (NRPS)-polyketide synthase (PKS), typical NRPS, enzymes synthesizing precursors for VM or VS, transporters for resistance, regulatory proteins, and auxiliary enzymes The involvement of the cloned gene cluster in VM biosynthesis was confirmed by gene disruption of virA encoding a hybrid PKSNRPS megasynthetase, which resulted in complete loss of VM production without any effect on VS production Present status on the regulation of the VM/VS biosynthesis, initiated by the binding of VB to VB-specific receptor, will be described and discussed * Corresponding author Tel.: 81-6-6879-7452 E-mail: nihira@icb.osaka-u.ac.jp