Crowdsourcing Natural Products Discovery to Access Uncharted Dimensions of Fungal Metabolite Diversity

Authors

  • Dr. Lin Du,

    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)
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    • These authors contributed equally to this work.

  • Andrew J. Robles,

    1. Department of Pharmacology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229 (USA)
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    • These authors contributed equally to this work.

  • Jarrod B. King,

    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)
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  • Dr. Douglas R. Powell,

    1. Department of Chemistry and Biochemistry, Stephenson Life Sciences Research Center, University of Oklahoma, 101 Stephenson Parkway Norman, OK 73019-5251 (USA)
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  • Prof. Dr. Andrew N. Miller,

    1. Illinois Natural History Survey, University of Illinois (USA)
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  • Prof. Dr. Susan L. Mooberry,

    Corresponding author
    1. Department of Pharmacology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229 (USA)
    2. Cancer Therapy & Research Center and Department of Medicine, University of Texas Health Science Center at San Antonio (USA)
    • Susan L. Mooberry, Department of Pharmacology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229 (USA)

      Robert H. Cichewicz, Department of Chemistry and Biochemistry, Stephenson Life Sciences Research Center, University of Oklahoma, 101 Stephenson Parkway Norman, OK 73019-5251 (USA)

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  • Prof. Dr. Robert H. Cichewicz

    Corresponding author
    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)
    • Susan L. Mooberry, Department of Pharmacology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229 (USA)

      Robert H. Cichewicz, Department of Chemistry and Biochemistry, Stephenson Life Sciences Research Center, University of Oklahoma, 101 Stephenson Parkway Norman, OK 73019-5251 (USA)

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Errata

This article is corrected by:

  1. Errata: Corrigendum: Crowdsourcing Natural Products Discovery to Access Uncharted Dimensions of Fungal Metabolite Diversity Volume 53, Issue 37, 9695, Article first published online: 2 September 2014
  2. Errata: Corrigendum: Crowdsourcing Natural Products Discovery to Access Uncharted Dimensions of Fungal Metabolite Diversity Volume 54, Issue 23, 6671, Article first published online: 27 May 2015

  • Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health RO1GM092219 (R.H.C.), the President’s Council Excellence Award (S.L.M.), and with support from the CTRC P30 Cancer Center Support Grant (CA054174) and the Flow Cytometry Shared Resource (S.L.M.). The X-ray diffractometer was purchased through a grant from the NSF (CHE-0130835). The LC-MS instrument used for this project was provided in part by a Challenge Grant from the Office of the Vice President for Research, University of Oklahoma, Norman Campus and an award through the Shimadzu Equipment Grant Program (R.H.C.). We gratefully acknowledge Ms. A. Reyor for supplying the soil sample used in this study.

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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