title: Swainsonine Biosynthesis Genes in Diverse Symbiotic and Pathogenic Fungi.
abstract: Swainsonine-a cytotoxic fungal alkaloid and a potential cancer therapy drug-is produced by the insect pathogen and plant symbiontMetarhizium robertsii, the clover pathogenSlafractonia leguminicola, locoweed symbionts belonging toAlternariasect.Undifilum, and a recently discovered morning glory symbiont belonging to order Chaetothyriales. Genome sequence analyses revealed that these fungi share orthologous gene clusters, designated "SWN," which included a multifunctionalswnKgene comprising predicted adenylylation and acyltransferase domains with their associated thiolation domains, a β-ketoacyl synthase domain, and two reductase domains. The role ofswnKwas demonstrated by inactivating it inM. robertsiithrough homologous gene replacement to give a ∆swnKmutant that produced no detectable swainsonine, then complementing the mutant with the wild-type gene to restore swainsonine biosynthesis. OtherSWNcluster genes were predicted to encode two putative hydroxylases and two reductases, as expected to complete biosynthesis of swainsonine from the predicted SwnK product.SWNgene clusters were identified in six out of seven sequenced genomes ofMetarhziumspecies, and in all 15 sequenced genomes of Arthrodermataceae, a family of fungi that cause athlete's foot and ringworm diseases in humans and other mammals. Representative isolates of all of these species were cultured, and allMetarhiziumspp. withSWNclusters, as well as all but one of the Arthrodermataceae, produced swainsonine. These results suggest a new biosynthetic hypothesis for this alkaloid, extending the known taxonomic breadth of swainsonine producers to at least four orders of Ascomycota, and suggest that swainsonine has roles in mutualistic symbioses and diseases of plants and animals.
authors.affiliation: Poisonous Plant Research Laboratory, United States Department of Agriculture-Agricultural Research Service, Logan, Utah 84321.
authors.forename: Daniel
authors.identifier: 0000-0001-8568-113X
authors.initials: D
authors.lastname: Cook
authors.affiliation: School of Integrative Plant Science, Cornell University, Ithaca, New York 14853.
authors.forename: Bruno G G
authors.initials: BGG
authors.lastname: Donzelli
authors.affiliation: Department of Entomology, Plant Pathology, and Weed Science, New Mexico State University, Las Cruces, New Mexico 88001.
authors.forename: Rebecca
authors.identifier: 0000-0002-5058-2980
authors.initials: R
authors.lastname: Creamer
authors.affiliation: Department of Entomology, Plant Pathology, and Weed Science, New Mexico State University, Las Cruces, New Mexico 88001.
authors.forename: Deana L
authors.initials: DL
authors.lastname: Baucom
authors.affiliation: Poisonous Plant Research Laboratory, United States Department of Agriculture-Agricultural Research Service, Logan, Utah 84321.
authors.forename: Dale R
authors.initials: DR
authors.lastname: Gardner
authors.affiliation: Department of Plant Pathology, University of Kentucky, Lexington, Kentucky 40546.
authors.forename: Juan
authors.initials: J
authors.lastname: Pan
authors.affiliation: Department of Computer Science, University of Kentucky, Lexington, Kentucky 40506.
authors.forename: Neil
authors.identifier: 0000-0003-4945-8074
authors.initials: N
authors.lastname: Moore
authors.affiliation: Robert W. Holley Center for Agriculture and Health, United States Department of Agriculture-Agricultural Research Service, Ithaca, New York 14853.
authors.forename: Stuart B
authors.identifier: 0000-0002-9147-074X
authors.initials: SB
authors.lastname: Krasnoff
authors.affiliation: Department of Computer Science, University of Kentucky, Lexington, Kentucky 40506.
authors.forename: Jerzy W
authors.identifier: 0000-0003-1427-4072
authors.initials: JW
authors.lastname: Jaromczyk
authors.affiliation: Department of Plant Pathology, University of Kentucky, Lexington, Kentucky 40546 chris.schardl@uky.edu.
authors.forename: Christopher L
authors.identifier: 0000-0003-2197-0842
authors.initials: CL
authors.lastname: Schardl
mesh_terms: D053898:Biosynthetic Pathways / Q000235:genetics*; D005658:Fungi / Q000235:genetics* / Q000378:metabolism* / Q000472:pathogenicity; D055785:Gene Knockdown Techniques; D005800:Genes, Fungal; D016681:Genome, Fungal; D023281:Genomics / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing; D005810:Multigene Family; D017026:Swainsonine / Q000378:metabolism*; D013559:Symbiosis; D014774:Virulence / Q000235:genetics
chemical_list: D017026:Swainsonine
keywords: comparative genomics; dermatophytes; locoweed endophyte; pathogenic fungi; symbiotic fungi