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Title: Insights into natural products biosynthesis from analysis of 490 polyketide synthases from Fusarium

item Brown, Daren
item Proctor, Robert

Submitted to: Fungal Genetics and Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/16/2016
Publication Date: 4/1/2016
Publication URL:
Citation: Brown, D.W., Proctor, R.H. 2016. Insights into natural products biosynthesis from analysis of 490 polyketide synthases from Fusarium. Fungal Genetics and Biology. 89:37-51.

Interpretive Summary: Fungi produce a numerous chemical compounds, some with beneficial properties (e.g. antibiotics) and others with harmful properties (e.g., toxins). Many of these compounds are formed via modifications to a class of molecules known as polyketides, which are formed by enzymes known as polyketide synthases (PKSs). The fungus Fusarium is of concern to agriculture because it causes disease on a wide range of plants and it produces toxins (also known as mycotoxins) that can accumulate in crops. The presence of Fusarium mycotoxins in crops poses a health risk to humans and other animals. For example, fumonisin mycotoxins are polyketide-derived compounds and can induce brain lesions in horses, fluid in the lungs of pigs, and cancer in laboratory rodents; and in some groups of humans, there is a positive correlation between consumption of fumonisin contaminated corn and cancer of the esophagus. To better understand production of polyketide-derived mycotoxins and other compounds in Fusarium, we identified all the genes that serve as blueprints for PKSs in 31 species of Fusarium. Analysis of the relationships of these genes to one another to a selection of PKS genes from other fungi, we obtained evidence that the Fusarium species examined produce 64 distinct polyketide-derived compounds. We also obtained evidence that the chemical structures of some of these compounds are very similar to compounds that were previously reported to be produced by other fungi. The results also indicate that the species examined vary tremendously in their ability to produce polyketide derived mycotoxins and other compounds. This research provides a foundation for understanding the diversity and distribution of polyketide-derived compounds produced by Fusarium. The results will be of use to plant pathologists, plant breeders, and other scientists involved in the development of new ways to reduce mycotoxin contamination in food crops.

Technical Abstract: Species of the fungus Fusarium collectively cause disease on almost all crop plants and produce numerous natural products (NPs), including some of the mycotoxins of greatest concern to agriculture. Many Fusarium NPs are derived from polyketide synthases, large multi-domain enzymes that catalyze sequential condensation of simple carboxylic acids to form polyketides. To gain insight into biosynthesis of polyketide-derived NPs in Fusarium, we retrieved 488 PKS gene sequences from genome sequences of 31 species of the fungus. In addition to these apparently functional PKS genes, the genomes collectively included 83 pseudogenized PKS genes. Phylogenetic analysis resolved the PKS genes into 67 clades, and based on multiple lines of evidence, we propose that homologs in each clade are responsible for synthesis of a polyketide that is distinct from those synthesized by PKSs in other clades. The presence and absence of PKS genes among the species examined indicated marked differences in distribution of PKS homologs. Comparisons of Fusarium PKS genes and genes flanking them to those from other Ascomycetes provided evidence that Fusarium has the genetic potential to synthesize multiple NPs that are the same or similar to those reported in other fungi, but that have not yet been reported in Fusarium. Our results point out some limitations of phylogenetic analyses and in silico comparisons of gene clusters for gaining insight into NP biosynthesis in fungi. However, the results also highlight ways in which such analyses can help guide identification of novel Fusarium NPs and differences in NP biosynthetic capabilities that exist among fungi.