Identification and distribution of a downregulatory signaling alkyloxazole in <i><i>Streptomyces</i></i>.

Abstract

<i><i>Streptomyces</i></i> use small molecules to dictate morphological development and secondary metabolism. Most of these signaling compounds are inducers derived from γ-butyrolactone (GBL)-synthesizing enzymes. As such, biosynthetically distinct and downregulatory signaling molecules remain understudied in <i><i>Streptomyces</i></i>. Here, we report the identification of alkyloxaozle (AOX, <b>1</b>), a downregulator of sporulation and antibiotic production in <i><i>Streptomyces</i></i>. <b>1</b>'s structure features an oxazole head flanked by an alkyl tail synthesized by a nonribosomal peptide synthetase (NRPS) that has not been reported in <i><i>Streptomyces</i></i> signaling molecules. Functional studies found that <b>1</b> downregulated sporulation and secondary metabolism in several <i><i>Streptomyces</i></i> strains. Genome mining identified 45 homologous biosynthetic gene clusters (BGCs) only distributed in <i><i>Streptomyces</i></i>, underscoring the importance of AOXs to this productive genus. Altogether, this report presents a downregulatory class of signaling molecules that broadly affect <i><i>Streptomyces</i></i> and highlights their importance to the genus.