Structure and Biosynthesis of Isatropolones, Bioactive Amine-Scavenging Fluorescent Natural Products from Streptomyces Gö66

  • Angew Chem Int Ed Engl. 2017 Apr 24;56(18):4945-4949. doi: 10.1002/anie.201701223.
Xiaofeng Cai  1 ,  Yi-Ming Shi  1 ,  Nicole Pöhlmann  2 ,  Ole Revermann  2 ,  Isabel Bahner  2 ,  Sacha J Pidot  3 ,  Frank Wesche  1 ,  Helmut Lackner  2 ,  Claudia Büchel  4 ,  Marcel Kaiser  5  6 ,  Christian Richter  7 ,  Harald Schwalbe  7 ,  Timothy P Stinear  3 ,  Axel Zeeck  2 ,  Helge B Bode  1  8
Affiliations
  • 1. Merck Stiftungsprofessur für Molekulare Biotechnologie, Fachbereich Biowissenschaften, Goethe-Universität Frankfurt, Max-von-Laue-Strasse 9, 60438, Frankfurt am Main, Germany.
  • 2. Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen, Germany.
  • 3. Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Australia.
  • 4. Institute of Molecular Biosciences, Goethe-Universität Frankfurt, Germany.
  • 5. Swiss Tropical and Public Health Institute, Parasite Chemotherapy, Basel, Switzerland.
  • 6. University of Basel, Switzerland.
  • 7. Institut für Organische Chemie und Chemische Biologie, Zentrum für Biomolekulare Magnetische Resonanz, Goethe-Universität Frankfurt, Germany.
  • 8. Buchmann Institute for Molecular Life Sciences (BMLS), Goethe-Universität Frankfurt, Germany.
PMID: 28371116 DOI: 10.1002/anie.201701223
Abstract

The natural products isatropolone A-C (1-3) were reisolated from Streptomyces Gö66, with 1 and 3 showing potent activity against Leishmania donovani. They contain a rare tropolone ring derived from a type II polyketide biosynthesis pathway. Their biosynthesis was elucidated by labeling experiments, analysis of the biosynthesis gene cluster, its partial heterologous expression, and structural characterization of various intermediates. Owing to their 1,5-diketone moiety, they can react with ammonia, amines, lysine, and lysine-containing peptides and proteins, which results in the formation of a covalent bond and subsequent pyridine ring formation. Their fluorescence properties change upon amine binding, enabling the simple visualization of reacted amines including proteins.

Keywords
1,5-diketones; fluorescence; isatropolones; natural products; rubrolones.
Products