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.
Dr. Lin Du1,4,‡, Andrew J. Robles2,‡,Jarrod B. King1,4, Dr. Douglas R. Powell1,Prof. Dr. Andrew N. Miller3, Prof. Dr. Susan L. Mooberry2,5,*, Prof. Dr. Robert H. Cichewicz
Angewandte Chemie International Edition
Article first published online: 27 NOV 2013