β-carboline chemical signals induce reveromycin production through a LuxR family regulator in Streptomyces sp. SN-593

Abstract

Actinomycetes bacteria produce diverse bioactive molecules that are useful as drug seeds. To improve their yield, researchers often optimize the fermentation medium. However, exactly how the extracellular chemicals present in the medium activate secondary metabolite gene clusters remains unresolved. BR-1, a β-carboline compound, was recently identified as a chemical signal that enhanced reveromycin A production in Streptomyces sp. SN-593. Here we show that BR-1 specifically bound to the transcriptional regulator protein RevU in the reveromycin A biosynthetic gene cluster, and enhanced RevU binding to its promoter. RevU belongs to the LuxR family regulator that is widely found in bacteria. Interestingly, BR-1 and its derivatives also enhanced the production of secondary metabolites in other Streptomyces species. Although LuxR-N-acyl homoserine lactone systems have been characterized in Gram-negative bacteria, we revealed LuxR-β-carboline system in Streptomyces sp. SN-593 for the production of secondary metabolites. This study might aid in understanding hidden chemical communication by β-carbolines.