title: Skipping in a hybrid polyketide synthase. Evidence for ACP-to-ACP chain transfer.
abstract: A tetraketide synthase containing a loading module (LM), the extension modules erythromycin module 1, rapamycin module 2, and erythromycin module 2 (LM-Ery1-Rap2-Ery2-TE), when expressed in Saccharopolyspora erythraea strain JC2, produced as previously reported a mixture of tetraketide lactones (minor products) and triketide lactones (major products). Several alternative plausible mechanisms by which this "skipping" phenomenon might occur may be proposed. Site-directed mutagenesis of the ketosynthase (KS) and acylcarrier protein (ACP) domains in the interpolated module has shown that skipping within the hybrid PKS involves passage of the growing polyketide through the interpolated module, by direct ACP-to-ACP transfer of the polyketide chain.
authors.affiliation: Cambridge Centre for Molecular Recognition and Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, CB2 1GA, Cambridge, United Kingdom.
authors.forename: Iain
authors.initials: I
authors.lastname: Thomas
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Martin
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Wilkinson
authors.forename: James
authors.initials: J
authors.lastname: Staunton
authors.forename: Peter F
authors.initials: PF
authors.lastname: Leadlay
mesh_terms: D000213:Acyl Carrier Protein / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D018942:Macrolides / Q000138:chemical synthesis / Q000378:metabolism; D008958:Models, Molecular; D009097:Multienzyme Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D010441:Peptide Chain Elongation, Translational / Q000235:genetics; D015202:Protein Engineering / Q000379:methods*; D017434:Protein Structure, Tertiary; D016930:Saccharopolyspora / Q000235:genetics / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000737:chemistry
chemical_list: D000213:Acyl Carrier Protein; D018942:Macrolides; D009097:Multienzyme Complexes; D013438:Sulfhydryl Compounds