These authors contributed equally to this work.
Crowdsourcing Natural Products Discovery to Access Uncharted Dimensions of Fungal Metabolite Diversity†
Article first published online: 27 NOV 2013
Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Angewandte Chemie International Edition
Volume 53, Issue 3, pages 804–809, January 13, 2014
How to Cite
Du, L., Robles, A. J., King, J. B., Powell, D. R., Miller, A. N., Mooberry, S. L. and Cichewicz, R. H. (2014), Crowdsourcing Natural Products Discovery to Access Uncharted Dimensions of Fungal Metabolite Diversity. Angew. Chem. Int. Ed., 53: 804–809. doi: 10.1002/anie.201306549
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.
- Issue published online: 8 JAN 2014
- Article first published online: 27 NOV 2013
- Manuscript Revised: 26 SEP 2013
- Manuscript Received: 26 JUL 2013
- National Institutes of Health. Grant Number: RO1GM092219
- NSF. Grant Number: CHE-0130835
- antitumor agents;
- drug discovery;
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.