HOMOLOGUES OF PLEOTROPIC REGULATORY GENE adpA IN ACTINOPLANES: ANALYSIS IN SIILICO

Abstract

Actinoplanes teichomyceticus produces glycopeptide antibiotic teicoplanin, a “last line defense” against multidrug resistant cocci. The gene cluster for biosynthesis of teicoplanin (tcp) has been cloned 8 years ago, although regulation of its production is poorly understood because of lack of genetic toolkit to manipulate this strain as well as knowledge of its genome organization. In streptomycetes, regulatory gene adpA encodes a master regulator of secondary and primary metabolism, as well morphogenesis, forming the largest gene “modulon” known to date for bacteria. Here we analyzed the possibility that AdpA-like protein might be involved in regulation of teicoplanin production. We used the described consensus AdpA operator sequences, inferred from analysis of streptomycete genomes, to screen the tcp cluster. Several putative AdpA operators were revealed within tcp cluster, implying that AdpA-like transcriptional factors may indeed operate in Actinoplanes. Using comparative genomic approaches, we revealed several putative adpA homologues in completely sequenced Actinoplanes genomes as well as in draft sequence of A. teichomyceticus genome. Taken together, our data strongly support the idea that adpA-mediated regulation influences the production of antibiotics not only in genus Streptomyces, but also in Actinoplanes.