The biosynthesis of the polyether antibiotic nanchangmycin is controlled by two pathway-specific transcriptional activators

The nanchangmycin (NAN) produced by NS3226 is a polyether antibiotic resembling monensin in their gene clusters and the chemical structures. They can inhibit gram-positive bacteria and be a growth promoter for ruminants. Within the nanchangmycin gene cluster (), we identified that two SARP-family regulatory genes, and , were both required to activate the transcription of all polyketide genes. Overexpression of NanR1 and NanR2 in wild-type increase NAN yields by at least three folds. Bioinformatic analysis of the immediate upstream DNA sequence of each gene and quantitative real-time RT-PCR analysis of the operons identified five putative SARP binding sites. Moreover, deletion of an AraC-family repressor gene increased expression of NanR1 and R2 and led to a threefold increase in NAN production.