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Angew Chem Int Ed Engl. 2014 Jan 13;53(3):804-9. doi: 10.1002/anie.201306549. Epub 2013 Nov 27.

Crowdsourcing natural products discovery to access uncharted dimensions of fungal metabolite diversity.

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1
Department of Chemistry and Biochemistry, Stephenson Life Sciences Research Center, University of Oklahoma, 101 Stephenson Parkway Norman, OK 73019-5251 (USA); Natural Products Discovery Group and Institute for Natural Products Applications and Research Technologies, University of Oklahoma (USA).

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Abstract

A fundamental component for success in drug discovery is the ability to assemble and screen compounds that encompass a broad swath of biologically relevant chemical-diversity space. Achieving this goal in a natural-products-based setting requires access to a wide range of biologically diverse specimens. For this reason, we introduced a crowdsourcing program in which citizen scientists furnish soil samples from which new microbial isolates are procured. Illustrating the strength of this approach, we obtained a unique fungal metabolite, maximiscin, from a crowdsourced Alaskan soil sample. Maximiscin, which exhibits a putative combination of polyketide synthase (PKS), non-ribosomal peptide synthetase (NRPS), and shikimate pathway components, was identified as an inhibitor of UACC-62 melanoma cells (LC50=0.93 μM). The metabolite also exhibited efficacy in a xenograft mouse model. These results underscore the value of building cooperative relationships between research teams and citizen scientists to enrich drug discovery efforts.

KEYWORDS:

antitumor agents; biosynthesis; crowdsourcing; drug discovery; epigenetics

PMID:
24285637
PMCID:
PMC4028707
DOI:
10.1002/anie.201306549
[Indexed for MEDLINE]
Free PMC Article
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