S54: Biosynthesis and genetic engineering of goadsporin, a linear thiazolylpeptide produced by Streptomyces sp. TP-A0584

Goadsporin is a promoting compound against to secondary metabolism and morphogenesis of a wide variety of Streptomyces genus. Goadsporin consists of 19 amino acids, which include 8 unusual amino acids, oxazole, thiazole, and dehydroalanine.

  A study of the biosynthetic gene cluster for goadsporin revealed that goadsporin is a ribosomally synthesized peptide. The goadsporin biosynthetic gene cluster contains a structural gene and 9 god genes, which together span 20 kb and are involved in posttranslational modification, immunity, and transcriptional regulation. Goadsporin biosynthesis is initiated by the translation of the mRNA coding for a 49-amino acid polypeptide (GodA). The subsequent cyclization to form oxazole and thiazole rings is probably catalyzed by GodD and GodE, and the dehydration to form dehydroalanine, by GodF and GodG. Finally, its N-terminal 30-amino acid leader sequence is digested, and the N-terminal is acetylated by GodH to afford goadsporin.

  By using the goadsporin biosynthetic system, we constructed over 50 analogs of goadsporin by codon replacement of godA and showed that the posttranslational heterocyclyzation of goadsporin complied with some rules and regulation. We will discuss the mechanism of generating these analogs and the applications of the biosynthetic engineering of thiopeptide analogs.