Phlorisovalerophenone synthase, a novel polyketide synthase from hop (Humulus lupulus L.) cones

Authors

  • Norma B. Paniego,

    1. Division of Pharmacognosy, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, PO Box 9502, 2300 RA Leiden, the Netherlands;
    2. Instituto de Biotecnología. Centro de Investigaciones Veterinarias y Agrarias. INTA Castelar. Las Cabañas y los Reseros, Villa Udaondo, Pcia Buenos Aires, Argentina
    Search for more papers by this author
  • Karin W. M. Zuurbier,

    1. Division of Pharmacognosy, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, PO Box 9502, 2300 RA Leiden, the Netherlands;
    Search for more papers by this author
  • Suen-Ying Fung,

    1. Division of Pharmacognosy, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, PO Box 9502, 2300 RA Leiden, the Netherlands;
    Search for more papers by this author
    • Robert van der Heijden,

      1. Division of Pharmacognosy, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, PO Box 9502, 2300 RA Leiden, the Netherlands;
      Search for more papers by this author
    • Johannes J. C. Scheffer,

      1. Division of Pharmacognosy, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, PO Box 9502, 2300 RA Leiden, the Netherlands;
      Search for more papers by this author
    • Robert Verpoorte

      1. Division of Pharmacognosy, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, PO Box 9502, 2300 RA Leiden, the Netherlands;
      Search for more papers by this author

    R. Verpoorte, Division of Pharmacognosy, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, PO Box 9502, 2300 RA Leiden, the Netherlands. Fax: + 31 71 527 45 11, Tel: + 31 71 527 45 10, E-mail: verpoort@lacdr.leidenuniv.nl

    Abstract

    Phlorisovalerophenone synthase (VPS), a novel aromatic polyketide synthase, was purified to homogeneity from 4.2 mg protein extract obtained from hop (Humulus lupulus L.) cone glandular hairs. The enzyme uses isovaleryl-CoA or isobutyryl-CoA and three molecules of malonyl-CoA to form phlorisovalerophenone or phlorisobutyrophenone, intermediates in the biosynthesis of the hop bitter acids (α- and β-acids). VPS is an homodimeric enzyme, with subunits of 45 kDa. The pI of the enzyme was 6.1. Km values of 4 µm for isovaleryl-CoA, 10 µm for isobutyryl-CoA and 33 µm for malonyl-CoA, were found. The amino-acid sequences of two peptides, obtained by digestion of VPS, showed that the enzyme is highly homologous to plant chalcone synthases. The functional and structural relationship between VPS and other aromatic polyketide synthases is discussed.

    Ancillary