Genomics and evolution of fungal gene clusters responsible for synthesis of sphinganine-analog metabolites of concern to human health and food safety

Authors: Kim, Hye-Seon; Proctor, Robert; Busman, Mark; Brown, Daren

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 8/23/2018
Publication Date: 8/23/2018
Citation: Kim, H.-S., Proctor, R., Busman, M., Brown, D.W. 2018. Genomics and evolution of fungal gene clusters responsible for synthesis of sphinganine-analog metabolites of concern to human health and food safety. [abstract].

Interpretive Summary:

Technical Abstract: Multiple microorganisms produce sphinganine-analog metabolites (SAMs), compounds that disrupt sphingolipid metabolism by virtue of structural similarities to the sphingoid base sphinganine. From the extensively studied biosynthetic pathway for fumonisins, a family of SAMs that are among the mycotoxins of greatest concern to agriculture, we predicted that biosynthesis of microbial SAMs requires three enzymes: a polyketide synthase (PKS), an amino transferase (AT), and a short-chain dehydrogenase/reductase (SDR). To begin to assess the potential structural diversity and distribution of (SAMs), we screened 343 genome sequences of the agriculturally important fungus Fusarium for gene clusters that include homologs of the fumonisin PKS, AT and SDR genes. The screen identified 194 potential SAM biosynthetic gene (SAM) clusters in 46% of the genomes. Phylogenetic analyses resolved the clusters into six homolog groups: the fumonisin cluster and clusters SAM1 – SAM5. We propose that each homolog group confers the ability to synthesize a structurally distinct SAM family. We predict that SAM5 confers the ability to synthesize the SAM 2-amino-14, 16-dimethyloctadecan-3-ol (AOD), because it is the only SAM cluster present in the AOD-producing species Fusarium avenaceum. The SAM products of the other clusters are unknown, but the gene content of the clusters suggests the products have relatively simple structures compared to fumonisins. There are 2-3 SAM clusters in some genomes, and all SAM clusters have a limited, and in some cases sporadic, distribution among the species examined. In addition, we found evidence that horizontal transfer has contributed to the sporadic distribution of some SAM clusters. These findings suggest that the ability to disrupt sphingolipid metabolism provides a selective advantage to some Fusarium species. Understanding what this advantage(s) is has the potential to identify strategies that reduce SAM contamination of crops.