Project description:Actinomycete genomes contain a plethora of orphan gene clusters encoding unknown secondary metabolites, and representing a huge unexploited pool of chemical diversity. The explosive increase in genome sequencing and the massive advance of bioinformatic tools have revolutionized the rationale for natural product discovery from actinomycetes. In this context, we applied a genome mining approach to discover a group of unique catecholate-hydroxamate siderophores termed as qinichelins from Streptomyces sp. MBT76. Quantitative proteomics statistically correlated a gene cluster of interest (qch) to its unknown chemotype (qinichelin), after which structural elucidation of isolated qinichelin was assisted by bioinformatics analysis and verified by MS2 and NMR experiments. Strikingly, intertwined functional crosstalk among four separately located gene clusters was implicated in the biosynthesis of qinichelins.
Project description:TenA-family proteins are widespread bacterial regulators with unknown roles in natural product biosynthesis. This study aimed to functionally characterize LysR2, a TenA-family protein in Actinobacteria, and elucidate its mechanism in regulating the production of lysolipin I. We demonstrate that LysR2 represents a novel type of regulator that controls antibiotic biosynthesis not by direct DNA binding, but through protein-protein interactions, specifically by antagonizing the repressor LysR1. This work reveals an unconventional regulatory strategy, expanding the mechanistic understanding of transcriptional networks in natural product formation.
