Evidence for a novel phosphopantetheinyl transferase domain in the polyketide synthase for enediyne biosynthesis.
The polyketide synthase associated with the biosynthesis of enediyne-containing calicheamicin contains a putative phosphopantetheinyl transferase (PPTase) domain. By cloning and expressing the C-terminal region of the polyketide synthase and in vitro phosphopantetheinylation assay, we found that the PPTase domain exhibits preferred substrate specificity towards acyl and peptidyl carrier proteins in fatty acid and non-ribosomal peptide synthesis over its cognate partner. We also found evidence suggesting that the PPTase domain adopts a pseudo-trimeric structure, distinct from the pseudo-dimeric structure of type II PPTases. The results revealed a novel type of PPTase with unique structure and substrate specificity, and suggested that the polyketide synthase probably acquired the PPTase domain from a primary metabolic pathway in evolution.
Murugan
Elavazhagan
E
Division of Chemical Biology and Biotechnology, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.
Liang
Zhao-Xun
ZX
D000213:Acyl Carrier Protein / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D000617:Aminoglycosides / Q000096:biosynthesis* / Q000737:chemistry; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D053281:Enediynes / Q000737:chemistry; D008969:Molecular Sequence Data; D048630:Polyketide Synthases / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D013379:Substrate Specificity; D017855:Transferases (Other Substituted Phosphate Groups) / Q000737:chemistry* / Q000378:metabolism
D000213:Acyl Carrier Protein; D000617:Aminoglycosides; D001426:Bacterial Proteins; D002352:Carrier Proteins; D053281:Enediynes; C489066:calicheamicin enediyne; C082662:phosphopantetheinyl transferase; D048630:Polyketide Synthases; D017855:Transferases (Other Substituted Phosphate Groups)