4 research outputs found
Identification by Gene Deletion Analysis of a Regulator, VmsR, That Controls Virginiamycin Biosynthesis in Streptomyces virginiae
Cluster organization of the genes of Streptomyces pristinaespiralis involved in pristinamycin biosynthesis and resistance elucidated by pulsed-field gel electrophoresis
Molecular Insights into the Biosynthesis of Guadinomine: A Type III Secretion System Inhibitor
Guadinomines are a recently discovered family of anti-infective compounds produced by Streptomyces sp. K01-0509 with a novel mode of action. With an IC(50) of 14 nM, guadinomine B is the most potent known inhibitor of the Type III Secretion System (TTSS) of Gram-negative bacteria. TTSS activity is required for the virulence of many pathogenic Gram-negative bacteria including Escherichia coli, Salmonella spp., Yersinia spp., Chlamydia spp., Vibrio spp., and Pseudomonas spp. The guadinomine (gdn) biosynthetic gene cluster has been cloned and sequenced, and includes 26 open reading frames spanning 51.2 kb. It encodes a chimeric multimodular polyketide synthase – nonribosomal peptide synthetase, along with enzymes responsible for the biosynthesis of the unusual aminomalonyl-ACP extender unit and the signature carbamoylated cyclic guanidine. Its identity was established by targeted disruption of the gene cluster, as well as by heterologous expression and analysis of key enzymes in the biosynthetic pathway. Identifying the guadinomine gene cluster provides critical insight into the biosynthesis of these scarce but potentially important natural products