Crowdsourcing Natural Products Discovery to Access Uncharted Dimensions of Fungal Metabolite Diversity1. Issue 3 (27th November 2013)

• Record Type: Journal Article
• Authors: Du, Lin; Robles, Andrew J.; King, Jarrod B.; Powell, Douglas R.; Miller, Andrew N.; Mooberry, Susan L.; Cichewicz, Robert H.
• Is Part Of: Angewandte Chemie international edition. Volume 53:Issue 3(2014)
• Page Start: 804
• Page End: 809
• Publication Date: 2013-11-27
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201306549
• Languages: English
• ISSNs: 1433-7851

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>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<sc>M</sc>). 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.</p> </abstract>