A non-canonical transcriptional regulation in natural product biosynthesis

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. RNA-Seq analysis was performed to identify differentially expressed genes between a lysR2 knockout mutant and the wild-type strain of the producer organism.