title: Architecture of the polyketide synthase module: surprises from electron cryo-microscopy.
abstract: Modular polyketide synthases (PKS) produce a vast array of bioactive molecules that are the basis of many highly valued pharmaceuticals. The biosynthesis of these compounds is based on ordered assembly lines of multi-domain modules, each extending and modifying a specific chain-elongation intermediate before transfer to the next module for further processing. The first 3D structures of a full polyketide synthase module in different functional states were obtained recently by electron cryo-microscopy. The unexpected module architecture revealed a striking evolutionary divergence of the polyketide synthase compared to its metazoan fatty acid synthase homolog, as well as remarkable conformational rearrangements dependent on its biochemical state during the full catalytic cycle. The design and dynamics of the module are highly optimized for both catalysis and fidelity in the construction of complex, biologically active natural products.
authors: Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: JanetSmith@umich.edu.
authors: Janet L
authors: JL
authors: Smith
authors: Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
authors: Georgios
authors: G
authors: Skiniotis
authors: Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Medicinal Chemistry, University of Michigan, Ann Arbor, MI 48109, USA; Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA; Department of Microbiology & Immunology, University of Michigan, Ann Arbor, MI 48109, USA.
authors: David H
authors: DH
authors: Sherman
mesh_terms: D000213:Acyl Carrier Protein / Q000378:metabolism; D000818:Animals; D020285:Cryoelectron Microscopy / Q000379:methods*; D019143:Evolution, Molecular; D006801:Humans; D048630:Polyketide Synthases / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary
chemical_list: D000213:Acyl Carrier Protein; D048630:Polyketide Synthases