Deciphering On-Off signalling network of Streptomyces secondary metabolism

• Main Author: Takuya, Nihira
• Format: Working Paper
• Language: English
• Published: 2011
• Subjects: ACM; Streptomyces; Enzymes synthesizing
• Online Access: http://repository.vnu.edu.vn/handle/123456789/9743
• Institution: Vietnam National University, Hanoi

Virginiamycin M (VM) of Streptomyces virginiae is a hybrid peptide-polyketide antibiotic with peptide antibiotic virginiamycin S (VS) as its synergistic counterpart. VM and VSbelong tothe Streptogramin family, which is character ized 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 controlof 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. virginiaein the 77-kb region including about 10-kb of the regulatory is land forvirginiamycin 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 virAencoding a hybrid PKS-NRPS 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.