Manipulation of metabolic pathways controlled by signaling molecules, inducers of antibiotic production, for genome mining in Streptomyces spp

Abstract

Streptomyces is well characterized by an ability to produce a wide variety of secondary metabolites including antibiotics, whose expression is strictly controlled by small diffusible signaling molecules at nano-molar concentrations. The signaling molecules identified to date are classified into three skeletons; γ-butyrolactones, furans, and γ-butenolides. Accumulated data suggest the structural diversity of the signaling molecules in Streptomyces species and their potential in activating cryptic secondary metabolite biosynthetic pathways. Several genome mining approaches to activate silent biosynthetic gene clusters have been reported for natural product discovery. This review updates recent examples on genetic manipulation including blockage of metabolic pathways together with inactivation of transcriptional repressor genes.

Keywords: Biosynthesis; Regulatory cascade; Secondary metabolites; Signaling molecule; Streptomyces.