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

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.

Antibiotic discovery is a walk in the park

“…Culturing efforts can even be distributed through citizen science projects, such as the Small World Initiative (www.smallworldinitiative. org/) and the Natural Product Discovery Group (npdg.ou.edu/ citizenscience) (14), and direct analysis of the metabolites' content can now be done by anyone using open crowd-sourced analysis platforms, such as Global Natural Product Social Molecular Networking (gnps.ucsd.edu) (15). One promising strategy for the valorization of potential therapeutical discovery from eDNA is to Charlop-Powers et al extracted DNA from the environment, followed by high-throughput sequencing of its genetic instructions, to reveal that your local park is an untapped resource with enormous potential for discovery of new therapeutics.…”

Building Natural Product Libraries Using Quantitative Clade-Based and Chemical Clustering Strategies

“…The Alternaria isolates used in this study were obtained through the University of Oklahoma, Citizen Science Soil Collection Program ( 38 , 39 ), which to date has received 9,670 soil samples from across the United States, yielding 78,581 fungal isolates identified by single-read internal transcribed spacer (ITS) sequencing data. A query performed on the ITS barcode data yielded an initial set of 219 candidate Alternaria isolates, which was refined to a subset of 198 samples having >90% ITS sequence similarity ( 40 – 42 ) to Alternaria type strain data available in GenBank and defined by Woudenberg et al ( 31 ).…”

The “Yin and Yang” of Natural Compounds in Anticancer Therapy of Triple-Negative Breast Cancers

“…Maximiscin ( Figure 2 J, Figure 3 and Figure 4 ), a fungal metabolite isolated from fungus Tolypocladium sp., was discovered as part of a crowdsourcing initiative in the USA [ 298 ]. Maximiscin treatment showed growth suppression and cytotoxic efficacy towards basal-like 1, MDA-MB-468 TNBC cells when compared to other molecular subtypes of TNBCs [ 186 ].…”