Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 558407
Title Antitumor astins originate from the endophyte Cyanodermella asteris living within the medicinal plant Aster tataricus
Author(s) Schafhauser, T.; Jahn, L.; Kirchner, Norbert; Kulik, Andreas; Flor, L.; Lang, A.; Caradec, T.; Fewer, D.P.; Sivonen, K.; Berkel, W.J.H. van; Jacques, P.; Weber, T.; Gross, H.; Pée, K.H. van; Wohlleben, W.; Ludwig-Müller, L.
Source Proceedings of the National Academy of Sciences of the United States of America 116 (2019)52. - ISSN 0027-8424 - p. 26909 - 26917.
DOI https://doi.org/10.1073/pnas.1910527116
Department(s) VLAG
Biochemistry
Publication type Refereed Article in a scientific journal
Publication year 2019
Abstract 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.
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