title: Insights into protein-protein and enzyme-substrate interactions in modular polyketide synthases.
abstract: Numerous natural products of clinical value are biosynthesized by polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs), which are multienzymes comprising modules of catalytic domains. The key players in each module are carrier proteins, which serve as attachment points for the growing substrate chains. Thus, the details of carrier protein-based substrate delivery to each active site are central to understanding chain assembly in these systems. In the enterobactin NRPS, communication between a peptidyl carrier protein (PCP) and the adjacent thioesterase (TE) domain occurs through formation of a compact complex. Using NMR, we show that the corresponding interaction between a PKS acyl carrier protein (ACP) and its downstream TE is fundamentally different: chain transfer occurs in the absence of a protein-protein interface, with contact limited to the substrate acyl terminus.
authors.affiliation: Department of Biochemistry, 80 Tennis Court Road, University of Cambridge, Cambridge CB21GA, UK.
authors.forename: Lucky
authors.initials: L
authors.lastname: Tran
authors.forename: R William
authors.initials: RW
authors.lastname: Broadhurst
authors.forename: Manuela
authors.initials: M
authors.lastname: Tosin
authors.forename: Andrea
authors.initials: A
authors.lastname: Cavalli
authors.forename: Kira J
authors.initials: KJ
authors.lastname: Weissman
mesh_terms: D000213:Acyl Carrier Protein / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D001051:Apoenzymes / Q000737:chemistry / Q000378:metabolism; D003067:Coenzymes / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010204:Pantetheine / Q000031:analogs & derivatives / Q000378:metabolism; D048630:Polyketide Synthases / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013237:Stereoisomerism; D013379:Substrate Specificity; D013869:Thiolester Hydrolases / Q000378:metabolism
chemical_list: D000213:Acyl Carrier Protein; D001051:Apoenzymes; D003067:Coenzymes; D010204:Pantetheine; D048630:Polyketide Synthases; D013869:Thiolester Hydrolases; C003129:4'-phosphopantetheine