title: Structure and Biosynthesis of Isatropolones, Bioactive Amine-Scavenging Fluorescent Natural Products from Streptomyces Gö66.
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.
authors.affiliation: Merck Stiftungsprofessur für Molekulare Biotechnologie, Fachbereich Biowissenschaften, Goethe-Universität Frankfurt, Max-von-Laue-Strasse 9, 60438, Frankfurt am Main, Germany.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Cai
authors.affiliation: Merck Stiftungsprofessur für Molekulare Biotechnologie, Fachbereich Biowissenschaften, Goethe-Universität Frankfurt, Max-von-Laue-Strasse 9, 60438, Frankfurt am Main, Germany.
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Shi
authors.affiliation: Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Pöhlmann
authors.affiliation: Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen, Germany.
authors.forename: Ole
authors.initials: O
authors.lastname: Revermann
authors.affiliation: Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen, Germany.
authors.forename: Isabel
authors.initials: I
authors.lastname: Bahner
authors.affiliation: Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Australia.
authors.forename: Sacha J
authors.initials: SJ
authors.lastname: Pidot
authors.affiliation: Merck Stiftungsprofessur für Molekulare Biotechnologie, Fachbereich Biowissenschaften, Goethe-Universität Frankfurt, Max-von-Laue-Strasse 9, 60438, Frankfurt am Main, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Wesche
authors.affiliation: Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen, Germany.
authors.forename: Helmut
authors.initials: H
authors.lastname: Lackner
authors.affiliation: Institute of Molecular Biosciences, Goethe-Universität Frankfurt, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Büchel
authors.affiliation: Swiss Tropical and Public Health Institute, Parasite Chemotherapy, Basel, Switzerland.|University of Basel, Switzerland.
authors.forename: Marcel
authors.initials: M
authors.lastname: Kaiser
authors.affiliation: Institut für Organische Chemie und Chemische Biologie, Zentrum für Biomolekulare Magnetische Resonanz, Goethe-Universität Frankfurt, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Richter
authors.affiliation: Institut für Organische Chemie und Chemische Biologie, Zentrum für Biomolekulare Magnetische Resonanz, Goethe-Universität Frankfurt, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Schwalbe
authors.affiliation: Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Australia.
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Stinear
authors.affiliation: Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Zeeck
authors.affiliation: Merck Stiftungsprofessur für Molekulare Biotechnologie, Fachbereich Biowissenschaften, Goethe-Universität Frankfurt, Max-von-Laue-Strasse 9, 60438, Frankfurt am Main, Germany.|Buchmann Institute for Molecular Life Sciences (BMLS), Goethe-Universität Frankfurt, Germany.
authors.forename: Helge B
authors.identifier: 0000-0001-6048-5909
authors.initials: HB
authors.lastname: Bode
mesh_terms: D000588:Amines / Q000378:metabolism; D000818:Animals; D000977:Antiparasitic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001688:Biological Products / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D053898:Biosynthetic Pathways; D002460:Cell Line; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007893:Leishmania donovani / Q000187:drug effects; D007898:Leishmaniasis, Visceral / Q000188:drug therapy / Q000469:parasitology; D005810:Multigene Family; D051381:Rats; D013302:Streptomyces / Q000737:chemistry / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D014334:Tropolone / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000588:Amines; D000977:Antiparasitic Agents; D001688:Biological Products; D005456:Fluorescent Dyes; D014334:Tropolone
keywords: 1,5-diketones; fluorescence; isatropolones; natural products; rubrolones