title: Evolution of Chemical Diversity in a Group of Non-Reduced Polyketide Gene Clusters: Using Phylogenetics to Inform the Search for Novel Fungal Natural Products.
abstract: Fungal polyketides are a diverse class of natural products, or secondary metabolites (SMs), with a wide range of bioactivities often associated with toxicity. Here, we focus on a group of non-reducing polyketide synthases (NR-PKSs) in the fungal phylum Ascomycota that lack a thioesterase domain for product release, group V. Although widespread in ascomycete taxa, this group of NR-PKSs is notably absent in the mycotoxigenic genus Fusarium and, surprisingly, found in genera not known for their secondary metabolite production (e.g., the mycorrhizal genus Oidiodendron, the powdery mildew genus Blumeria, and the causative agent of white-nose syndrome in bats, Pseudogymnoascus destructans). This group of NR-PKSs, in association with the other enzymes encoded by their gene clusters, produces a variety of different chemical classes including naphthacenediones, anthraquinones, benzophenones, grisandienes, and diphenyl ethers. We discuss the modification of and transitions between these chemical classes, the requisite enzymes, and the evolution of the SM gene clusters that encode them. Integrating this information, we predict the likely products of related but uncharacterized SM clusters, and we speculate upon the utility of these classes of SMs as virulence factors or chemical defenses to various plant, animal, and insect pathogens, as well as mutualistic fungi.
authors.affiliation: Department of Genetics, University of Wisconsin-Madison, 425 Henry Mall, Madison, WI 53706-1580, USA. kthrockmorto@wisc.edu.
authors.forename: Kurt
authors.initials: K
authors.lastname: Throckmorton
authors.affiliation: Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, 1550 Linden Drive, Madison, WI 53706-1521, USA. pwiemann@wisc.edu.
authors.forename: Philipp
authors.initials: P
authors.lastname: Wiemann
authors.affiliation: Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, 1550 Linden Drive, Madison, WI 53706-1521, USA. npkeller@wisc.edu.
authors.forename: Nancy P
authors.initials: NP
authors.lastname: Keller
mesh_terms: D001203:Ascomycota / Q000145:classification / Q000201:enzymology / Q000235:genetics*; D001688:Biological Products / Q000378:metabolism*; D019143:Evolution, Molecular; D054884:Host-Pathogen Interactions; D005810:Multigene Family; D010802:Phylogeny; D048630:Polyketide Synthases / Q000235:genetics* / Q000378:metabolism; D013559:Symbiosis / Q000235:genetics
chemical_list: D001688:Biological Products; D048630:Polyketide Synthases
keywords: : mycotoxin; evolution; gene cluster; polyketide synthase