Date of Award
D. Cole Stevens
The importance of natural product discovery to society is undeniable as natural products have seemingly infinite applications, particularly in regard to pharmacological use as antibacterial, antifungal, antiparasitic, anticancer and immunosuppressive agents. The search for new therapeutics and other new chemical commodities thus grows simultaneously with antibiotic resistance and commercial pressure on pharmaceutical research. However, the increasingly common phenomenon of natural product rediscovery continues to inhibit advancement in this field. We contend that the likelihood of rediscovery can be predicted by taxonomic distance between the bacteria in question and previously studied bacteria. That is, our data supports a correlation between chemical diversity and taxonomic distance, and we offer the hopeful perspective that less commonly explored genera have outstanding potential for unique natural product discovery. Specifically, we have examined the order Myxococcales, a reputable source of secondary metabolites. Our findings have been facilitated by the mining of bacterial genomes for biosynthetic gene clusters (BGCs), a methodology that has become a critical component to natural product discovery as it takes advantage of the increasing number of sequenced bacterial genomes available through public databases. By using the BiG-SCAPE-CORASON platform to generate sequence similarity networks that contain 994 BGCs identified by antiSMASH from 36 sequenced myxobacteria, we have observed that every predicted BGC was specific to one of three current suborders of myxobacteria. The analysis of BGCs detected within four additional, draft genomes supports the observation that myxobacterial biosynthetic diversity correlates with taxonomic distance and suggests the likelihood of rediscovery when targeting previously investigated genera. Further, 822 BGCs with no notable homology to characterized clusters within the MIBiG database are presented. This survey portrays the biosynthetic diversity of these BGCs and exemplifies the potential for natural product discovery from myxobacteria. Herein we report the likelihood for rediscovery of known metabolites from bacteria belonging to previously explored genera. The results depict significant biosynthetic potential of bacteria associated with overlooked taxa within the Myxococcales and possibly other natural product-associated bacteria orders.
Gregory, Katherine C., "Survey of Biosynthetic Gene Clusters from Sequenced Myxobacteria and Analysis of Potential Metabolic Diversity" (2019). Honors Theses. 1115.