Biosynthesis of the Novel Macrolide Antibiotic Anthracimycin

2015-11-20T11:34:55Z (GMT) by Silke Alt Barrie Wilkinson
We report the identification of the biosynthetic gene cluster for the unusual antibiotic anthracimycin (<i>atc</i>) from the marine derived producer strain Streptomyces sp. T676 isolated off St. John’s Island, Singapore. The 53 253 bps <i>atc</i> locus includes a <i>trans</i>-acyltransferase (<i>trans</i>-AT) polyketide synthase (PKS), and heterologous expression in Streptomyces coelicolor resulted in anthracimycin production. Analysis of the <i>atc</i> cluster revealed that anthracimycin is likely generated by four PKS gene products AtcC–AtcF without involvement of <i>post</i>-PKS tailoring enzymes, and a biosynthetic pathway is proposed. The availability of the <i>atc</i> cluster provides a basis for investigating the biosynthesis of anthracimycin and its subsequent bioengineering to provide novel analogues with improved pharmacological properties.