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Substrate Specificity in Ketosynthase Domains from trans-AT Polyketide Synthases

Authors

  • Matthew Jenner,

    1. School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD (UK)
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  • Sarah Frank,

    1. Kekulé Institute of Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Strasse 1, 53121 Bonn (Germany)
    2. Institute of Microbiology, Eidgenössische Technische Hochschule (ETH) Zurich, Wolfgang-Pauli-Strasse 10, 8083 Zurich (Switzerland)
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  • Annette Kampa,

    1. Kekulé Institute of Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Strasse 1, 53121 Bonn (Germany)
    2. Institute of Microbiology, Eidgenössische Technische Hochschule (ETH) Zurich, Wolfgang-Pauli-Strasse 10, 8083 Zurich (Switzerland)
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  • Christoph Kohlhaas,

    1. Kekulé Institute of Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Strasse 1, 53121 Bonn (Germany)
    2. Institute of Microbiology, Eidgenössische Technische Hochschule (ETH) Zurich, Wolfgang-Pauli-Strasse 10, 8083 Zurich (Switzerland)
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  • Petra Pöplau,

    1. Kekulé Institute of Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Strasse 1, 53121 Bonn (Germany)
    2. Institute of Microbiology, Eidgenössische Technische Hochschule (ETH) Zurich, Wolfgang-Pauli-Strasse 10, 8083 Zurich (Switzerland)
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  • Dr. Geoff S. Briggs,

    1. School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD (UK)
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  • Prof. Dr. Jörn Piel,

    Corresponding author
    1. Kekulé Institute of Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Strasse 1, 53121 Bonn (Germany)
    2. Institute of Microbiology, Eidgenössische Technische Hochschule (ETH) Zurich, Wolfgang-Pauli-Strasse 10, 8083 Zurich (Switzerland)
    • Kekulé Institute of Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Strasse 1, 53121 Bonn (Germany)
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  • Dr. Neil J. Oldham

    Corresponding author
    1. School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD (UK)
    • School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD (UK)
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  • We are grateful for financial support by the Biotechnology and Biological Science Research Council (BBSRC) and the University of Nottingham to N.J.O. and the DFG (SFB 624 and PI 430/8-1) to J.P.

Abstract

original image

Branching out: The substrate specificity profiles for a range of ketosynthase (KS) domains from trans-AT PKSs are reported. Evidence is provided that a sterically demanding amino acid residue adjacent to the active-site Cys residue confers specificity towards non-β-methyl-branched substrates (see scheme).

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