Biosynthesis of the Novel Macrolide Antibiotic Anthracimycin

We report the identification of the biosynthetic gene cluster for the unusual antibiotic anthracimycin (atc) from the marine derived producer strain Streptomyces sp. T676 isolated off St. John's Island, Singapore. The 53,253 bps ate locus includes a trans-acyltransferase (trans AT) polyketide synthase (PKS), and heterologous expression in Streptomyces coelicolor resulted in anthracimycin production. Analysis of the atc cluster revealed that anthracimycin is likely generated By four PKS gene products AtcC-AtcF without involvement of post-PKS tailoring enzymes, and a biosynthetic pathway is proposed. The availability of the atc cluster provides a, basis for investigating the biosynthesis of anthracimycin and its subsequent bioengineering to pro-Vide novel analogues with improved pharmacological properties.