Angew. Chem. Int. Ed.http://doi.org/f2nz62 (2013)
Fungal natural products include a diverse range of chemical structures and often possess interesting biological properties — such as anticancer or antimicrobial activity. However, it is difficult to collect and isolate a large range of fungal species to analyse, and so far only a small percentage of metabolites from fungal species has been tested for bioactivity. Taking a collaborative approach to this problem, a team led by Susan Mooberry and Robert Cichewicz from the University of Texas Health Science Center and the University of Oklahoma respectively, enlisted the help of 'citizen scientists' to collect soil samples from different regions. Crowdsourcing sample collection enabled them to isolate and analyse metabolites from a greater range of fungal species.
This approach led to the discovery of a previously unknown natural product, which the team called maximiscin. They found that by altering the culture medium for a strain of crowdsourced Tolypocladium, or by co-culturing the strain with a species of bacteria, they could switch on an otherwise silent biosynthetic pathway that led to this natural product. The team probed the biosynthetic origins of maximiscin by including isotope-labelled precursors in the culture medium and identifying where they were incorporated into the structure. These labelling experiments revealed that maximiscin consists of two moieties that are synthesized by different biosynthetic pathways. One moiety is produced via the known 'shikimate pathway', and the other via a route that includes a polyketide synthase and a non-ribosomal peptide synthetase. These two moieties are linked by an unusual O=C–N–O–C bridge.
Maximiscin was shown to possess useful anticancer properties. Screening tests revealed that the natural product inhibited the growth of several cancer cell lines. Follow-up studies using a mouse model of cancer demonstrated that it can also significantly inhibit tumour growth in mice. The team say that crowdsourcing approaches can enable research teams to obtain information that would otherwise be inaccessible, whilst also engaging the public in the scientific process.
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Johnson, R. Crowdsourcing drug discovery. Nature Chem 6, 87 (2014). https://doi.org/10.1038/nchem.1867