Distribution of lactone-signaling system for expression of secondary metabolite biosynthetic gene clusters in <i>Streptomyces</i> species

Many Streptomyces species have a signaling-molecule/receptor system for induction of secondary metabolite biosynthetic gene clusters (BGCs). Signaling molecules hitherto discovered and studied contain five-membered heterocycles, and are classified into three groups, including γ-butyrolactones, γ-butenolides, and furans. These molecules except for avenolide-type are biosynthesized by enzymes harboring an AfsA tandem repeat domain. These enzymes (AfsA homologs) catalyze a transfer of β-ketoacyl moiety to the hydroxyl group of dihydroxyacetone phosphate. Alignment of 59 afsA homolog genes showed that 86% (51/59) of them located adjacent to their possible signaling-molecule receptor genes, which reminds us to readily predict their signaling-molecule/receptor system for expression of BGCs. Apparent exception is the case of afsA-arpA system in Streptomyces griseus, whose distance was around 3.91 Mb. Understanding of the signaling-molecule/receptor system may lead to a practical genome mining strategy to awaken silent BGCs through derepression of transcription using the cognate ligands, signaling molecules.