Evidence for a novel phosphopantetheinyl transferase domain in the polyketide synthase for enediyne biosynthesis

• Published in: FEBS letters 2008-04, Vol.582 (7), p.1097-1103
• Main Authors: Murugan, Elavazhagan, Liang, Zhao-Xun
• Format: Article
• Language: English
• Subjects: ACP; ACP domain from the modular PKS DEBS; ACP domain of the iterative PKS in calicheamicin biosynthesis (M. echinospora ssp.); ACP from E. coli fatty acid synthesis pathway; AcpS; Acyl carrier protein; Acyl Carrier Protein - chemistry; Acyl Carrier Protein - metabolism; acyl carrier protein synthase; Amino Acid Sequence; Aminoglycosides - biosynthesis; Aminoglycosides - chemistry; Bacterial Proteins - chemistry; Bacterial Proteins - metabolism; Calicheamicin; carrier protein; Carrier Proteins - chemistry; Carrier Proteins - metabolism; DACP; EACP; Enediyne; Enediynes - chemistry; FAS; fatty acid synthase; GPCP; meACP; Molecular Sequence Data; non-ribosomal peptide synthase; NRPS; PCP; PCP domain of non-ribosomal peptide synthase (GrsA B. brevis); peptidyl carrier protein; Phosphopantetheinyl transferase; PKS; Polyketide synthase; Polyketide Synthases - chemistry; Polyketide Synthases - metabolism; PPTase; Protein Structure, Tertiary; Sequence Alignment; Substrate Specificity; Transferases (Other Substituted Phosphate Groups) - chemistry; Transferases (Other Substituted Phosphate Groups) - metabolism
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2008.02.061

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.