title: Role of a conserved arginine residue in linkers between the ketosynthase and acyltransferase domains of multimodular polyketide synthases.
abstract: The role of interdomain linkers in modular polyketide synthases is poorly understood. Analysis of the 6-deoxyerythronolide B synthase (DEBS) has yielded a model in which chain elongation is governed by interactions between the acyl carrier protein domain and the ketosynthase domain plus an adjacent linker. Alanine scanning mutagenesis of the conserved residues of this linker in DEBS module 3 led to the identification of the R513A mutant with a markedly reduced rate of chain elongation. Limited proteolysis supported a structural role for this Arg. Our findings highlight the importance of domain-linker interactions in assembly line polyketide biosynthesis.
authors.affiliation: Department of Chemistry, Stanford University, Stanford, California 94305, USA.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yuzawa
authors.forename: Shiven
authors.initials: S
authors.lastname: Kapur
authors.forename: David E
authors.initials: DE
authors.lastname: Cane
authors.forename: Chaitan
authors.initials: C
authors.lastname: Khosla
mesh_terms: D000213:Acyl Carrier Protein / Q000737:chemistry; D000217:Acyltransferases / Q000737:chemistry; D001120:Arginine / Q000737:chemistry / Q000378:metabolism*; D004917:Erythromycin / Q000031:analogs & derivatives / Q000096:biosynthesis; D008958:Models, Molecular; D048630:Polyketide Synthases / Q000737:chemistry* / Q000235:genetics; D017434:Protein Structure, Tertiary; D016930:Saccharopolyspora / Q000201:enzymology / Q000235:genetics
chemical_list: D000213:Acyl Carrier Protein; C034277:6-deoxyerythronolide B; D004917:Erythromycin; D048630:Polyketide Synthases; D001120:Arginine; D000217:Acyltransferases