Genome mining reveals the origin of a bald phenotype and a cryptic nucleocidin gene cluster in Streptomyces asterosporus DSM 41452

Streptomyces asterosporus DSM 41452 is a producer of the polyketide annimycin and the non-ribosomal depsipeptide WS9326A. This strain is also notable for exhibiting a bald phenotype that is devoid of spores and aerial mycelium when grown on solid media. Based on the similarity of the 16S rRNA sequence to Streptomyces calvus, the only known producer of the fluorometabolite nucleocidin, the genome of S. asterosporus DSM 41452 was sequenced and analyzed. Twenty-nine natural product gene clusters were detected in the genome, including a gene cluster predicted to encode the fluorometabolite nucleocidin. Through genome analysis and gene complementation experiments, we demonstrate that the bald phenotype arises from a transposon gene inserted within the promoter sequence for the pleiotropic regulator adpA. Complementation of S. asterosporus DSM 41452 with a functional adpA sequence restored morphological differentiation and promoted the production of nucleocidin.