The Stereochemistry of Complex Polyketide Biosynthesis by Modular Polyketide Synthases
department or school: Science, Faculty of
department or school: Non UBC
department or school: Chemistry, Department of
data provider: DSpace
identifier citation: Molecules 16 (7): 6092-6115 (2011)
creator: Kwan, David H.
creator: Schulz, Frank
issued: 2019-04-04T15:56:54Z
issued: 2011-07-20
description: Polyketides are a diverse class of medically important natural products whose biosynthesis is catalysed by polyketide synthases (PKSs), in a fashion highly analogous to fatty acid biosynthesis. In modular PKSs, the polyketide chain is assembled by the successive condensation of activated carboxylic acid-derived units, where chain extension occurs with the intermediates remaining covalently bound to the enzyme, with the growing polyketide tethered to an acyl carrier domain (ACP). Carboxylated acyl-CoA precursors serve as activated donors that are selected by the acyltransferase domain (AT) providing extender units that are added to the growing chain by condensation catalysed by the ketosynthase domain (KS). The action of ketoreductase (KR), dehydratase (DH), and enoylreductase (ER) activities can result in unreduced, partially reduced, or fully reduced centres within the polyketide chain depending on which of these enzymes are present and active. The PKS-catalysed assembly process generates stereochemical diversity, because carbon–carbon double bonds may have either cis- or trans- geometry, and because of the chirality of centres bearing hydroxyl groups (where they are retained) and branching methyl groups (the latter arising from use of propionate extender units). This review shall cover the studies that have determined the stereochemistry in many of the reactions involved in polyketide biosynthesis by modular PKSs.
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/69456
note: Molecules 2011, 16, 6092-6115; doi:10.3390/molecules16076092 molecules ISSN 1420-3049 www.mdpi.com/journal/molecules Review The Stereochemistry of Complex Polyketide Biosynthesis by Modular Polyketide Synthases David H. Kwan 1,* and Frank Schulz 2,3,* 1 Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver B.C., V6T 1Z1, Canada 2 Fakultät für Chemie, Chemische Biologie, Technische Universität Dortmund, Otto-Hahn-Straße 6, 44221 Dortmund, Germany 3 Max-Planck-Institut für Molekulare Physiologie, Abteilung für Chemische Biologie, Otto-Hahn- Straße 11, 44227 Dortmund, Germany * Authors to whom correspondence should be addressed; E-Mails: dkwan@chem.ubc.ca (D.H.K.); frank3.schulz@tu-dortmund.de (F.S.); Tel.: +1-604-822-9300 (D.H.K.); +49-231-133-2429 (F.S.); Fax: +1-604-822-9126 (D.H.K.); +49-231-133-2498 (F.S.). Received: 8 June 2011; in revised form: 6 July 2011 / Accepted: 18 July 2011 / Published: 20 July 2011 Abstract: Polyketides are a diverse class of medically important natural products whose biosynthesis is catalysed by polyketide synthases (PKSs), in a fashion highly analogous to fatty acid biosynthesis. In modular PKSs, the polyketide chain is assembled by the successive condensation of activated carboxylic acid-derived units, where chain extension occurs with the intermediates remaining covalently bound to the enzyme, with the growing polyketide tethered to an acyl carrier domain (ACP). Carboxylated acyl-CoA precursors serve as activated donors that are selected by the acyltransferase domain (AT) providing extender units that are added to the growing chain by condensation catalysed by the ketosynthase domain (KS). The action of ketoreductase (KR), dehydratase (DH), and enoylreductase (ER) activities can result in unreduced, partially reduced, or fully reduced centres within the polyketide chain depending on which of these enzymes are present and active. The PKS-catalysed assembly process generates stereochemical diversity, becaus…
has type: Article
is shown at: 10.14288/1.0377811
language: eng
peer review status: Reviewed
provider: Vancouver : University of British Columbia Library
publisher: Multidisciplinary Digital Publishing Institute
publisher DOI: 10.3390/molecules16076092
rights: CC BY 3.0
rights URI: https://creativecommons.org/licenses/by-nc-sa/3.0/
scholar level: Faculty
subject: Polyketides
subject: Polyketide synthase
subject: Stereochemistry
subject: Ketosynthase
subject: Acyltransferase
subject: Ketoreductase
subject: Dehydratase
subject: Enoylreductase
type: Text
identifier URI: http://hdl.handle.net/2429/69456