Article (Scientific journals)
Antitumor astins originate from the fungal endophyte Cyanodermella asteris living within the medicinal plant Aster tataricus
Schafhauser, T.; Jahn, L.; Kirchner, N. et al.
2019In Proceedings of the National Academy of Sciences of the United States of America, 116 (52), p. 26909-26917
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Keywords :
Astin; Cross-species biosynthesis; Medicinal plant; Natural product; NRPS; Article; Aster tataricus; Cyanodermella asteris; Lecanoromycetes
Abstract :
[en] Medicinal plants are a prolific source of natural products with remarkable chemical and biological properties, many of which have considerable remedial benefits. Numerous medicinal plants are suffering from wildcrafting, and thus biotechnological production processes of their natural products are urgently needed. The plant Aster tataricus is widely used in traditional Chinese medicine and contains unique active ingredients named astins. These are macrocyclic peptides showing promising antitumor activities and usually containing the highly unusual moiety 3,4-dichloroproline. The biosynthetic origins of astins are unknown despite being studied for decades. Here we show that astins are produced by the recently discovered fungal endophyte Cyanodermella asteris. We were able to produce astins in reasonable and reproducible amounts using axenic cultures of the endophyte. We identified the biosynthetic gene cluster responsible for astin biosynthesis in the genome of C. asteris and propose a production pathway that is based on a nonribosomal peptide synthetase. Striking differences in the production profiles of endophyte and host plant imply a symbiotic cross-species biosynthesis pathway for astin C derivatives, in which plant enzymes or plant signals are required to trigger the synthesis of plant-exclusive variants such as astin A. Our findings lay the foundation for the sustainable biotechnological production of astins independent from aster plants. © 2019 National Academy of Sciences. All rights reserved.
Disciplines :
Microbiology
Author, co-author :
Schafhauser, T.;  Microbiology and Biotechnology, Interfaculty Institute of Microbiology and Infection Medicine, Eberhard Karls University Tübingen, Tübingen, 72076, Germany, Institute of Botany, Technische Universität Dresden, Dresden, 01217, Germany, General Biochemistry, Technische Universität Dresden, Dresden, 01062, Germany
Jahn, L.;  Institute of Botany, Technische Universität Dresden, Dresden, 01217, Germany
Kirchner, N.;  Pharmaceutical Institute, Department of Pharmaceutical Biology, Eberhard Karls University Tübingen, Tübingen, 72076, Germany
Kulik, A.;  Microbiology and Biotechnology, Interfaculty Institute of Microbiology and Infection Medicine, Eberhard Karls University Tübingen, Tübingen, 72076, Germany
Flor, L.;  General Biochemistry, Technische Universität Dresden, Dresden, 01062, Germany
Lang, A.;  General Biochemistry, Technische Universität Dresden, Dresden, 01062, Germany
Caradec, T.;  Institut Charles Viollette, Equipe d'Accueil 7394, University of Lille, Lille, 59000, France
Fewer, D. P.;  Department of Microbiology, University of Helsinki, Helsinki, 00014, Finland
Sivonen, K.;  Department of Microbiology, University of Helsinki, Helsinki, 00014, Finland
Van Berkel, W. J. H.;  Laboratory of Biochemistry, Wageningen University and Research, Wageningen, 6708 WE, Netherlands
Jacques, Philippe ;  Université de Liège - ULiège > Département GxABT > Microbial, food and biobased technologies
Weber, T.;  Microbiology and Biotechnology, Interfaculty Institute of Microbiology and Infection Medicine, Eberhard Karls University Tübingen, Tübingen, 72076, Germany, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kgs. Lyngby, 2800, Denmark
Gross, H.;  Pharmaceutical Institute, Department of Pharmaceutical Biology, Eberhard Karls University Tübingen, Tübingen, 72076, Germany
Van Pée, K.-H.;  General Biochemistry, Technische Universität Dresden, Dresden, 01062, Germany
Wohlleben, W.;  Microbiology and Biotechnology, Interfaculty Institute of Microbiology and Infection Medicine, Eberhard Karls University Tübingen, Tübingen, 72076, Germany
Ludwig-Müller, J.;  Institute of Botany, Technische Universität Dresden, Dresden, 01217, Germany
More authors (6 more) Less
Language :
English
Title :
Antitumor astins originate from the fungal endophyte Cyanodermella asteris living within the medicinal plant Aster tataricus
Publication date :
2019
Journal title :
Proceedings of the National Academy of Sciences of the United States of America
ISSN :
0027-8424
eISSN :
1091-6490
Publisher :
National Academy of Sciences
Volume :
116
Issue :
52
Pages :
26909-26917
Peer reviewed :
Peer Reviewed verified by ORBi
Name of the research project :
Project Astinprod; Project ACTS 053.80.713
Funders :
UE - Union Européenne [BE]
Free State of Saxony
Sächsische Staatsministerium für Wissenschaft und Kunst
SAB - Sächsische Aufbaubank [DE]
University of Tübingen [DE]
BMBF - Bundesministerium für Bildung und Forschung [DE]
ULille - Université de Lille [FR]
JAES - Jane and Aatos Erkko Foundation [FI]
NWO - Nederlandse Organisatie voor Wetenschappelijk Onderzoek [NL]
NNF - Novo Nordisk Foundation [DK]
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