Computational and genomic approaches for natural product discovery in the fungus Fusarium

Authors: Kim, Hye-Seon; Vaughan, Martha; Busman, Mark; McCormick, Susan; Brown, Daren; Proctor, Robert

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 8/17/2019
Publication Date: 8/17/2019
Citation: Kim, H., Vaughan, M.M., Busman, M., McCormick, S.P., Brown, D.W., Proctor, R. 2019. Computational and genomic approaches for natural product discovery in the fungus Fusarium [abstract].

Interpretive Summary:

Technical Abstract: SUMMARY Fungi produce numerous natural products that are not essential for life but instead allow fungi to grow and compete in certain environments. These products, also known as secondary metabolites (SMs), can have toxic, plant growth promoting, or pharmaceutical properties (e.g., antimicrobial activity). On fungal chromosomes, genes required for biosynthesis of a particular SM are typically located adjacent to one another in a biosynthetic gene cluster (BGC). Using computational, phylogenetic and comparative genomic approaches, we identified 15,647 BGCs in genome sequences of 203 species of the agriculturally important fungus Fusarium. Our results demonstrate the value of genome sequencing for understanding and exploiting fungal chemical diversity. I. INTRODUCTION Fungi are often described as both friend and foe because they can produce a wide variety of fungal secondary metabolites (SMs) that can have positive (antibiotics, penicillin, anti-cholesterol; lovastatin and plant growth promoting; gibberellins) and negative effects (mycotoxins) on humans, animals and agriculture. Fusarium is a species-rich genus of fungi that are well known for their ability to produce a structurally diverse SMs, including mycotoxins, plant hormones, pigments, and other compounds with potential biotechnological impact. In addition, Fusarium is one of the most agriculturally important fungal genera because of the ability of many species to cause severe crop diseases and contaminate grain with mycotoxins (e.g., fumonisins and trichothecenes) that are of concern to food and feed safety. Fungal SMs are diverse in biological activity and chemical structure. The genes encoding enzymes that synthesize the same SM are typically located adjacent to one another in biosynthetic gene clusters (BGCs). Advances in genome sequencing technologies have markedly improved our ability to identify BGC in fungi and our understanding of the distribution of BGC across the phylogenetically diverse fungal genera such as Fusarium. This will in turn aid efforts to exploit the chemical diversity of fungi and to control mycotoxin contamination problems. II. OBJECTIVES AND RESULTS A. Objectives of this study Determine the distribution of BGCs in Fusarium species, identify novel BGCs and predict which species have the genetic potential to produce both harmful mycotoxins and beneficial SMs. B. Computational biology and genomic analysis We identified 15,647 known and putative BGCs, including six novel BGCs responsible for the synthesis of sphinganine analog metabolites (SAMs), a class of compounds that disrupt lipid metabolism. C. Impacts of this study Our results provide information on the potential health risks posed by different Fusarium species and have potential to facilitate discovery of novel and beneficial SMs. III. ILLUSTRATIONS Investigation of the genetic diversity of SM BGCs in 343 Fusarium genomes representing 203 species revealed marked variation in their distribution. Some of Fusarium species are exposed to co-occurrence of multiple BGCs either harmful and beneficial SMs.