title: Genome of Diaporthe sp. provides insights into the potential inter-phylum transfer of a fungal sesquiterpenoid biosynthetic pathway.
abstract: Fungi have highly active secondary metabolic pathways which enable them to produce a wealth of sesquiterpenoids that are bioactive. One example is Δ6-protoilludene, the precursor to the cytotoxic illudins, which are pharmaceutically relevant as anticancer therapeutics. To date, this valuable sesquiterpene has only been identified in members of the fungal division Basidiomycota. To explore the untapped potential of fungi belonging to the division Ascomycota in producing Δ6-protoilludene, we isolated a fungal endophyte Diaporthe sp. BR109 and show that it produces a diversity of terpenoids including Δ6-protoilludene. Using a genome sequencing and mining approach 17 putative novel sesquiterpene synthases were identified in Diaporthe sp. BR109. A phylogenetic approach was used to predict which gene encodes Δ6-protoilludene synthase, which was then confirmed experimentally. These analyses reveal that the sesquiterpene synthase and its putative sesquiterpene scaffold modifying cytochrome P450(s) may have been acquired by inter-phylum horizontal gene transfer from Basidiomycota to Ascomycota. Bioinformatic analyses indicate that inter-phylum transfer of these minimal sequiterpenoid secondary metabolic pathways may have occurred in other fungi. This work provides insights into the evolution of fungal sesquiterpenoid secondary metabolic pathways in the production of pharmaceutically relevant bioactive natural products.
authors: Yale University, Dept. of Molecular Biophysics and Biochemistry, 800 West Campus Drive, West Haven, CT 06516, USA; EMBRAPA - Empresa Brasileira de Pesquisa Agropecuária-Coastal Tablelands, Av. Beira Mar, 3250, Jardins, 49025-040 Aracaju, SE, Brazil.
authors: Jose Guedes
authors: JG
authors: de Sena Filho
authors: University of Minnesota, Dept. of Biochemistry, Molecular Biology and Biophysics, 1479 Gortner Avenue, St Paul, MN 55108, USA.
authors: Maureen B
authors: MB
authors: Quin
authors: Yale University, Dept. of Molecular Biophysics and Biochemistry, 800 West Campus Drive, West Haven, CT 06516, USA.
authors: Daniel J
authors: DJ
authors: Spakowicz
authors: Yale University, Dept. of Molecular Biophysics and Biochemistry, 800 West Campus Drive, West Haven, CT 06516, USA.
authors: Jeffrey J
authors: JJ
authors: Shaw
authors: Yale University, Dept. of Molecular Biophysics and Biochemistry, 800 West Campus Drive, West Haven, CT 06516, USA.
authors: Kaury
authors: K
authors: Kucera
authors: Yale University, Dept. of Molecular Biophysics and Biochemistry, 800 West Campus Drive, West Haven, CT 06516, USA.
authors: Brian
authors: B
authors: Dunican
authors: Yale University, Dept. of Molecular Biophysics and Biochemistry, 800 West Campus Drive, West Haven, CT 06516, USA.
authors: Scott A
authors: SA
authors: Strobel
authors: University of Minnesota, Dept. of Biochemistry, Molecular Biology and Biophysics, 1479 Gortner Avenue, St Paul, MN 55108, USA. Electronic address: schmi232@umn.edu.
authors: Claudia
authors: C
authors: Schmidt-Dannert
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism; D001203:Ascomycota / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D053898:Biosynthetic Pathways; D019295:Computational Biology; D060026:Endophytes / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D019143:Evolution, Molecular; D022761:Gene Transfer, Horizontal; D016681:Genome, Fungal; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D012717:Sesquiterpenes / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D012717:Sesquiterpenes
keywords: Anticancer; Ascomycota; Biosynthesis; Evolution; Natural products; Sesquiterpene synthase