The biochemical basis for stereochemical control in polyketide biosynthesis.

Journal of the American Chemical Society
Chiara ValenzanoD E Cane

Abstract

One of the most striking features of complex polyketides is the presence of numerous methyl- and hydroxyl-bearing stereogenic centers. To investigate the biochemical basis for the control of polyketide stereochemistry and to establish the timing and mechanism of the epimerization at methyl-bearing centers, a series of incubations was carried out using reconstituted components from a variety of modular polyketide synthases. In all cases the stereochemistry of the product was directly correlated with the intrinsic stereospecificity of the ketoreductase domain, independent of the particular chain elongation domains that were used, thereby establishing that methyl group epimerization, when it does occur, takes place after ketosynthase-catalyzed chain elongation. The finding that there were only minor differences in the rates of product formation observed for parallel incubations using an epimerizing ketoreductase domain and the nonepimerizing ketoreductase domain supports the proposal that the epimerization is catalyzed by the ketoreductase domain itself.

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Citations

Jan 27, 2011·Biotechnology Letters·Naseem KhanPatrick Caffrey
Oct 12, 2010·Journal of the American Chemical Society·Chiara R ValenzanoDavid E Cane
May 11, 2013·Journal of the American Chemical Society·Young-Ok YouDavid E Cane
Sep 4, 2012·The Journal of Organic Chemistry·Yit-Heng Chooi, Yi Tang
Mar 1, 2012·Proceedings of the National Academy of Sciences of the United States of America·Shiven KapurChaitan Khosla
Jun 5, 2010·The Journal of Biological Chemistry·David E Cane
May 7, 2010·Nucleic Acids Research·Swadha AnandDebasisa Mohanty
May 29, 2012·Nature Chemical Biology·Jianting ZhengAdrian T Keatinge-Clay
May 17, 2011·Journal of Molecular Biology·Jianting Zheng, Adrian T Keatinge-Clay
Dec 20, 2012·Critical Reviews in Biochemistry and Molecular Biology·Wei XuYi Tang
Jan 1, 2012·Computational and Structural Biotechnology Journal·Patrick Caffrey
Jul 28, 2016·The Journal of Antibiotics·David E Cane
Feb 6, 2017·Journal of the American Chemical Society·Xinqiang XieDavid E Cane
Apr 11, 2017·Chemical Reviews·Adrian T Keatinge-Clay
Apr 22, 2017·Journal of the American Chemical Society·Xinqiang XieDavid E Cane
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Nov 26, 2019·Israel Journal of Chemistry·Chaitan Khosla
Mar 19, 2013·Chembiochem : a European Journal of Chemical Biology·Yi ZouShuangjun Lin
Nov 8, 2013·Chemical Communications : Chem Comm·Amanda Jane HughesAdrian T Keatinge-Clay
Jan 11, 2018·Synthetic and Systems Biotechnology·Jesus F BarajasJay D Keasling
Nov 14, 2020·Chembiochem : a European Journal of Chemical Biology·Erin E DrufvaConstance B Bailey

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