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 atc 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 provide novel analogues with improved pharmacological properties.
Department of Molecular Microbiology, John Innes Centre , Norwich Research Park, Norwich, Norfolk NR4 7UH, United Kingdom.
Silke
S
Alt
Department of Molecular Microbiology, John Innes Centre , Norwich Research Park, Norwich, Norfolk NR4 7UH, United Kingdom.
Barrie
B
Wilkinson
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D015394:Molecular Structure; D005810:Multigene Family / Q000235:genetics; D061065:Polyketides / Q000737:chemistry / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D016415:Sequence Alignment; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism
D000900:Anti-Bacterial Agents; D061065:Polyketides; D029701:Saccharomyces cerevisiae Proteins; C583934:anthracimycin