Discovery of a family of gamma-aminobutyrate ureas via rational derepression of a silent bacterial gene cluster

作者：Sidda John D; Song Lijiang; Poon Vincent; Al Bassam Mahmoud; Lazos Orestis; Buttner Mark J; Challis Gregory L; Corre Christophe^*

来源：Chemical Science, 2014, 5(1): 86-89.

DOI：10.1039/c3sc52536h

Gaburedins, a family of gamma-aminobutyrate (GABA)-derived ureas, have been discovered by deletion of gbnR, an arpA-like putative transcriptional repressor in Streptomyces venezuelae ATCC 10712. Comparison of metabolite profiles in the wild type and mutant strains revealed six metabolites in the mutant that are lacking from the wild type. The structure of gaburedin A was established by HRMS combined with 1- and 2-D NMR spectroscopy and was confirmed by total synthesis. The other metabolites were confirmed as congeners using HRMS, MS/MS and feeding of putative biosynthetic precursors. Two genes, gbnA and gbnB, are proposed to be involved in gaburedin biosynthesis. Consistent with this hypothesis, deletion of gbnB in the gbnR mutant abolished gaburedin production. This is the first report to disclose the discovery of novel natural products via rational deletion of a putative pathway-specific regulatory gene.

• 出版日期2014