A noncanonical transcriptional regulation in natural product biosynthesis.

ABSTRACT: TenA (transcription enhancement) family proteins are widespread in bacteria, yet their functions in regulating natural product biosynthesis remain largely unexplored. Here, we report that LysR2, a TenA-family protein encoded by the lysolipin I biosynthetic gene cluster, acts as a transcriptional activator. Genetic and biochemical analyses reveal that LysR2 employs a noncanonical mechanism. Lacking a standard DNA-binding domain, it does not bind target promoters directly. Instead, LysR2 activates transcription by specifically binding to the pathway-specific repressor, LysR1. This protein-protein interaction displaces LysR1 from its cognate promoter, thereby derepressing the transcription of the biosynthetic gene cluster. Our work provides the first experimental evidence for a regulatory rol

SUBMITTER: Wang J 

PROVIDER: S-EPMC12817078 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature