title: A close look at a ketosynthase from a trans-acyltransferase modular polyketide synthase.
abstract: The recently discovered trans-acyltransferase modular polyketide synthases catalyze the biosynthesis of a wide range of bioactive natural products in bacteria. Here we report the structure of the second ketosynthase from the bacillaene trans-acyltransferase polyketide synthase. This 1.95 Å resolution structure provides the highest resolution view available of a modular polyketide synthase ketosynthase and reveals a flanking subdomain that is homologous to an ordered linker in cis-acyltransferase modular polyketide synthases. The structure of the cysteine-to-serine mutant of the ketosynthase acylated by its natural substrate provides high-resolution details of how a native polyketide intermediate is bound and helps explain the basis of ketosynthase substrate specificity. The substrate range of the ketosynthase was further investigated by mass spectrometry.
authors: Department of Molecular Biosciences, The University of Texas at Austin, 1 University Station A5300, Austin, TX 78712, USA.
authors: Darren C
authors: DC
authors: Gay
authors: Department of Molecular Biosciences, The University of Texas at Austin, 1 University Station A5300, Austin, TX 78712, USA.
authors: Glen
authors: G
authors: Gay
authors: Department of Chemistry, The University of Texas at Austin, 1 University Station A5300, Austin, TX 78712, USA.
authors: Abram J
authors: AJ
authors: Axelrod
authors: School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
authors: Matthew
authors: M
authors: Jenner
authors: Kekulé Institute of Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Straße 1, 53121 Bonn, Germany.
authors: Christoph
authors: C
authors: Kohlhaas
authors: Kekulé Institute of Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Straße 1, 53121 Bonn, Germany.
authors: Annette
authors: A
authors: Kampa
authors: School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
authors: Neil J
authors: NJ
authors: Oldham
authors: Kekulé Institute of Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Straße 1, 53121 Bonn, Germany; Institute of Microbiology, Eidgenössische Technische Hochschule (ETH) Zürich, Vladimir-Prelog-Weg 1-5/10, 8093 Zürich, Switzerland.
authors: Jörn
authors: J
authors: Piel
authors: Department of Molecular Biosciences, The University of Texas at Austin, 1 University Station A5300, Austin, TX 78712, USA; Department of Chemistry, The University of Texas at Austin, 1 University Station A5300, Austin, TX 78712, USA. Electronic address: adriankc@utexas.edu.
authors: Adrian T
authors: AT
authors: Keatinge-Clay
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D003545:Cysteine / Q000737:chemistry / Q000235:genetics; D013058:Mass Spectrometry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D048630:Polyketide Synthases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D012694:Serine / Q000737:chemistry / Q000235:genetics; D013379:Substrate Specificity
chemical_list: D012694:Serine; D048630:Polyketide Synthases; D003545:Cysteine