title: Penicillium roqueforti PR toxin gene cluster characterization.
abstract: PR toxin is a well-known isoprenoid mycotoxin almost solely produced by Penicillium roqueforti after growth on food or animal feed. This mycotoxin has been described as the most toxic produced by this species. In this study, an in silico analysis allowed identifying for the first time a 22.4-kb biosynthetic gene cluster involved in PR toxin biosynthesis in P. roqueforti. The pathway contains 11 open reading frames encoding for ten putative proteins including the major fungal terpene cyclase, aristolochene synthase, involved in the first farnesyl-diphosphate cyclization step as well as an oxidoreductase, an oxidase, two P450 monooxygenases, a transferase, and two dehydrogenase enzymes. Gene silencing was used to study three genes (ORF5, ORF6, and ORF8 encoding for an acetyltransferase and two P450 monooxygenases, respectively) and resulted in 20 to 40% PR toxin production reductions in all transformants proving the involvement of these genes and the corresponding enzyme activities in PR toxin biosynthesis. According to the considered silenced gene target, eremofortin A and B productions were also affected suggesting their involvement as biosynthetic intermediates in this pathway. A PR toxin biosynthesis pathway is proposed based on the most recent and available data.
authors.affiliation: Université de Brest, EA 3882 Laboratoire Universitaire de Biodiversité et d'Ecologie Microbienne, IBSAM, ESIAB, Technopôle Brest-Iroise, Plouzané, 29280, Brest, France.
authors.forename: Pedro I
authors.initials: PI
authors.lastname: Hidalgo
authors.affiliation: Université de Brest, EA 3882 Laboratoire Universitaire de Biodiversité et d'Ecologie Microbienne, IBSAM, ESIAB, Technopôle Brest-Iroise, Plouzané, 29280, Brest, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Poirier
authors.affiliation: mAbxience, Upstream Production, Parque Tecnológico de León, Julia Morros s/n, Armunia, 24009, León, Spain.
authors.forename: Ricardo V
authors.initials: RV
authors.lastname: Ullán
authors.affiliation: Université de Brest, EA 3882 Laboratoire Universitaire de Biodiversité et d'Ecologie Microbienne, IBSAM, ESIAB, Technopôle Brest-Iroise, Plouzané, 29280, Brest, France.
authors.forename: Justine
authors.initials: J
authors.lastname: Piqueras
authors.affiliation: Université de Brest, EA 3882 Laboratoire Universitaire de Biodiversité et d'Ecologie Microbienne, IBSAM, ESIAB, Technopôle Brest-Iroise, Plouzané, 29280, Brest, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Meslet-Cladière
authors.affiliation: Université de Brest, EA 3882 Laboratoire Universitaire de Biodiversité et d'Ecologie Microbienne, IBSAM, ESIAB, Technopôle Brest-Iroise, Plouzané, 29280, Brest, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Coton
authors.affiliation: Université de Brest, EA 3882 Laboratoire Universitaire de Biodiversité et d'Ecologie Microbienne, IBSAM, ESIAB, Technopôle Brest-Iroise, Plouzané, 29280, Brest, France. monika.coton@univ-brest.fr.
authors.forename: Monika
authors.initials: M
authors.lastname: Coton
mesh_terms: D000123:Acetyltransferases / Q000235:genetics; D053898:Biosynthetic Pathways / Q000235:genetics*; D020868:Gene Silencing; D006899:Mixed Function Oxygenases / Q000235:genetics; D005810:Multigene Family / Q000235:genetics*; D009183:Mycotoxins / Q000235:genetics* / Q000378:metabolism*; D009284:Naphthols / Q000378:metabolism*; D016366:Open Reading Frames / Q000235:genetics; D010407:Penicillium / Q000235:genetics* / Q000472:pathogenicity*; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes / Q000378:metabolism
chemical_list: D009183:Mycotoxins; D009284:Naphthols; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes; C015857:eremofortin A; D006899:Mixed Function Oxygenases; D000123:Acetyltransferases; C015483:PR Toxin
keywords: Biosynthesis pathway; Gene silencing; Mycotoxins; PR toxin; Penicillium roqueforti