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Crowdsourcing Natural Products Discovery to Access Uncharted Dimensions of Fungal Metabolite Diversity
Author(s) -
Du Lin,
Robles Andrew J.,
King Jarrod B.,
Powell Douglas R.,
Miller Andrew N.,
Mooberry Susan L.,
Cichewicz Robert H.
Publication year - 2014
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201306549
Subject(s) - crowdsourcing , drug discovery , metabolite , computational biology , polyketide , chemical space , virtual screening , biology , fungal diversity , biochemistry , computer science , enzyme , world wide web , ecology , biosynthesis
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 μ M ). 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.