The natural world has provided humanity with a plethora of molecules enabling major advancesin modern medicine and agriculture. Fungi are one of most prolific providers of such chemicals,yet represent perhaps the most understudied source of natural products. With often >50 naturalproduct biosynthetic gene clusters (BGCs) per strain, and only ~3% of fungal natural productsknown, fungi contain a wealth of new molecules ready to exploit in research. In this SBIR proposal,Enkay Omics, Inc. will refine its scalable platform (FungalMGx) to discover novel fungal naturalproducts through a fruitful union of bioinformatics, genomics and metabolomics. We aredifferentiated from the handful of other startups by virtue of a "grow and go" philosophy, whereinwe do not require upfront molecular or synthetic biology approaches yet can uncover hundredsof new natural scaffolds and the BGCs that produce them. This competitive advantage will beextended, protected, and used to partner with other companies to accelerate the exploitation ofnew natural products in the private sector. At the core of FungalMGx is the "metabologenomics" platform, previously applied tocollections of >1000 strains of Actinomycete bacteria. The MGx platform involves prediction ofBGCs from genome sequence data, clustering into gene cluster families (GCFs), collection oflarge-scale metabolomics data, and statistical correlation of gene cluster families to metabolites.However, FungalMGx is more than just applying the metabologenomics platform to fungi -through the use of our customized fungi-specific informatics tools, we will improve the precisionof bioinformatic tools for BGC and GCF annotation and improve our compound discovery platformthat will be portable to any strain collection of future clients and partners. This will position EnKayOmics as a leading service provider to regularize fungi into an organized chemical library for"smart" integration with bioassays conducted by future partners seeking potent "agriphores" forantifungals, insecticides, and herbicides. In this SBIR, we will de-risk the use of combined metabolomics and genomics in fungi, asthis is distinct from implementation in bacteria and not been accomplished to date. Specifically,we will establish a library of fungal biosynthetic potential through the analysis of 4,000 publicly-available sequenced fungal genomes (Aim 1). Further, we use the organized set of ~150,000gene clusters to correlate and score the metabolites detected in extracts of 140 sequenced fungalstrains. In Aim 2, we develop a client-facing interface called Prospect, enabling lead prioritizationand data visualization for diverse genomic and metabolomics datasets. The goal of FUNGALMGXis to establish correlative NP discovery in fungi as a viable service and position us as efficientproviders of prioritized metabolites to private sector partners such as Varigen Biosciences, ClueGenetics, and "Big Ag" (e.g., Corteva Agriscience). Once refined, our unique platform and marketpositioning will differentiate us from other genome mining startups, and secure partnerships in theagrochemical and pharmaceutical sectors.
Public Health Relevance Statement: Narrative
This industrial research will lead to new service capabilities for an Illinois startup company that uses a correlative
approach to unearth new medicines from fungi. The work will expand a new approach to discovery and smart
prioritization of thousands of new chemicals from fungal extracts to serve as a new source for hits and leads in
drug screening campaigns. The work also involves assignment of the genes in the fungi that produce the natural
products and to begin strategic partnerships with private sector partners in the agriculture and pharmaceutical
sectors.
Project Terms: <6-Methylcompactin>
