Biomaterial Database

Structure of a modular polyketide synthase. 2014

Somnath Dutta, and Jonathan R Whicher, and Douglas A Hansen, and Wendi A Hale, and Joseph A Chemler, and Grady R Congdon, and Alison R H Narayan, and Kristina Håkansson, and David H Sherman, and Janet L Smith, and Georgios Skiniotis

1] Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA [2].

Polyketide natural products constitute a broad class of compounds with diverse structural features and biological activities. Their biosynthetic machinery, represented by type I polyketide synthases (PKSs), has an architecture in which successive modules catalyse two-carbon linear extensions and keto-group processing reactions on intermediates covalently tethered to carrier domains. Here we used electron cryo-microscopy to determine sub-nanometre-resolution three-dimensional reconstructions of a full-length PKS module from the bacterium Streptomyces venezuelae that revealed an unexpectedly different architecture compared to the homologous dimeric mammalian fatty acid synthase. A single reaction chamber provides access to all catalytic sites for the intramodule carrier domain. In contrast, the carrier from the preceding module uses a separate entrance outside the reaction chamber to deliver the upstream polyketide intermediate for subsequent extension and modification. This study reveals for the first time, to our knowledge, the structural basis for both intramodule and intermodule substrate transfer in polyketide synthases, and establishes a new model for molecular dissection of these multifunctional enzyme systems.

UI	MeSH Term	Description	Entries
D008958	Models, Molecular	Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.	Molecular Models,Model, Molecular,Molecular Model
D013302	Streptomyces	A genus of bacteria that form a nonfragmented aerial mycelium. Many species have been identified with some being pathogenic. This genus is responsible for producing a majority of the ANTI-BACTERIAL AGENTS of practical value.
D048630	Polyketide Synthases	Large enzyme complexes composed of a number of component enzymes that are found in STREPTOMYCES which biosynthesize MACROLIDES and other polyketides.	Polyketide Synthase,6-Deoxyerythronolide-B Synthase,Epothilone Polyketide Synthase,Erythromycin Polyketide Synthase,Griseusin Polyketide Synthase,Niddamycin Polyketide Synthase,Polyketide Synthase L1,Polyketide Synthase WA,Rifamycin Polyketide Synthase,Sterigmatocystin Polyketide Synthase,Type I Polyketide Synthase,Type II Polyketide Beta-Ketoacyl Synthase,Urdamycin Polyketide Synthase,WdPKS1 Protein,WhiE Polyketide Synthase,6 Deoxyerythronolide B Synthase,Polyketide Synthase, Epothilone,Polyketide Synthase, Erythromycin,Polyketide Synthase, Griseusin,Polyketide Synthase, Niddamycin,Polyketide Synthase, Rifamycin,Polyketide Synthase, Sterigmatocystin,Polyketide Synthase, Urdamycin,Polyketide Synthase, WhiE,Protein, WdPKS1,Synthase L1, Polyketide,Synthase WA, Polyketide,Synthase, 6-Deoxyerythronolide-B,Synthase, Epothilone Polyketide,Synthase, Erythromycin Polyketide,Synthase, Griseusin Polyketide,Synthase, Niddamycin Polyketide,Synthase, Polyketide,Synthase, Rifamycin Polyketide,Synthase, Sterigmatocystin Polyketide,Synthase, Urdamycin Polyketide,Synthase, WhiE Polyketide,Synthases, Polyketide,Type II Polyketide Beta Ketoacyl Synthase
D055162	Biocatalysis	The facilitation of biochemical reactions with the aid of naturally occurring catalysts such as ENZYMES.
D018942	Macrolides	A group of often glycosylated macrocyclic compounds formed by chain extension of multiple PROPIONATES cyclized into a large (typically 12, 14, or 16)-membered lactone. Macrolides belong to the POLYKETIDES class of natural products, and many members exhibit ANTIBIOTIC properties.	Macrolide
D020134	Catalytic Domain	The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.	Active Site,Catalytic Core,Catalytic Region,Catalytic Site,Catalytic Subunit,Reactive Site,Active Sites,Catalytic Cores,Catalytic Domains,Catalytic Regions,Catalytic Sites,Catalytic Subunits,Core, Catalytic,Cores, Catalytic,Domain, Catalytic,Domains, Catalytic,Reactive Sites,Region, Catalytic,Regions, Catalytic,Site, Active,Site, Catalytic,Site, Reactive,Sites, Active,Sites, Catalytic,Sites, Reactive,Subunit, Catalytic,Subunits, Catalytic
D020285	Cryoelectron Microscopy	Electron microscopy involving rapid freezing of the samples. The imaging of frozen-hydrated molecules and organelles permits the best possible resolution closest to the living state, free of chemical fixatives or stains.	Electron Cryomicroscopy,Cryo-electron Microscopy,Cryo electron Microscopy,Cryo-electron Microscopies,Cryoelectron Microscopies,Cryomicroscopies, Electron,Cryomicroscopy, Electron,Electron Cryomicroscopies,Microscopies, Cryo-electron,Microscopies, Cryoelectron,Microscopy, Cryo-electron,Microscopy, Cryoelectron
D064429	Fatty Acid Synthases	Enzymes that catalyze the synthesis of FATTY ACIDS from acetyl-CoA and malonyl-CoA derivatives.	Fatty Acid Synthase,Fatty Acid Synthetases,Acid Synthase, Fatty,Acid Synthases, Fatty,Synthase, Fatty Acid,Synthetases, Fatty Acid