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 536733
Title HEx : A heterologous expression platform for the discovery of fungal natural products
Author(s) Harvey, Colin J.B.; Tang, Mancheng; Schlecht, Ulrich; Horecka, Joe; Fischer, Curt R.; Lin, Hsiao Ching; Li, Jian; Naughton, Brian; Cherry, James; Miranda, Molly; Li, Yong Fuga; Chu, Angela M.; Hennessy, James R.; Vandova, Gergana A.; Inglis, Diane; Aiyar, Raeka S.; Steinmetz, Lars M.; Davis, Ronald W.; Medema, Marnix H.; Sattely, Elizabeth; Khosla, Chaitan; Onge, Robert P.S.; Tang, Yi; Hillenmeyer, Maureen E.
Source Science Advances 4 (2018)4. - ISSN 2375-2548
DOI http://dx.doi.org/10.1126/sciadv.aar5459
Department(s) Bioinformatics
EPS
Publication type Refereed Article in a scientific journal
Publication year 2018
Abstract For decades, fungi have been a source of U.S. Food and Drug Administration-approved natural products such as penicillin, cyclosporine, and the statins. Recent breakthroughs in DNA sequencing suggest that millions of fungal species exist on Earth, with each genome encoding pathways capable of generating as many as dozens of natural products. However, the majority of encoded molecules are difficult or impossible to access because the organisms are uncultivable or the genes are transcriptionally silent. To overcome this bottleneck in natural product discovery, we developed the HEx (Heterologous EXpression) synthetic biology platform for rapid, scalable expression of fungal biosynthetic genes and their encoded metabolites in Saccharomyces cerevisiae. We applied this platform to 41 fungal biosynthetic gene clusters from diverse fungal species from around the world, 22 of which produced detectable compounds. These included novel compounds with unexpected biosynthetic origins, particularly from poorly studied species. This result establishes the HEx platform for rapid discovery of natural products from any fungal species, even those that are uncultivable, and opens the door to discovery of the next generation of natural products.
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