Crowdsourcing Natural Products Discovery to Access Uncharted Dimensions of Fungal Metabolite Diversity |
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| Authors: | Dr Lin Du Andrew J Robles Jarrod B King Dr Douglas R Powell Prof?Dr Andrew N Miller Prof?Dr Susan L Mooberry Prof?Dr Robert H Cichewicz |
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| Affiliation: | 1. Department of Chemistry and Biochemistry, Stephenson Life Sciences Research Center, University of Oklahoma, 101 Stephenson Parkway Norman, OK 73019‐5251 (USA);2. Natural Products Discovery Group and Institute for Natural Products Applications and Research Technologies, University of Oklahoma (USA);3. Department of Pharmacology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229 (USA);4. Illinois Natural History Survey, University of Illinois (USA);5. Cancer Therapy & Research Center and Department of Medicine, University of Texas Health Science Center at San Antonio (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. |
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| Keywords: | antitumor agents biosynthesis crowdsourcing drug discovery epigenetics |
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