title: Fusarium Tri4 encodes a multifunctional oxygenase required for trichothecene biosynthesis.
abstract: Fusarium graminearum and Fusarium sporotrichioides produce the trichothecene mycotoxins 15-acetyldeoxynivalenol and T-2 toxin, respectively. In both species, disruption of the P450 monooxygenase-encoding gene, Tri4, blocks production of the mycotoxins and leads to the accumulation of the trichothecene precursor trichodiene. To further characterize its function, the F. graminearum Tri4 (FgTri4) was heterologously expressed in the trichothecene-nonproducing species Fusarium verticillioides. Transgenic F. verticillioides carrying the FgTri4 converted exogenous trichodiene to the trichothecene biosynthetic intermediates isotrichodermin and trichothecene. Conversion of trichodiene to isotrichodermin requires seven biochemical steps. The fifth and sixth steps can occur nonenzymatically. Precursor feeding studies done in the current study indicate that wild-type F. verticillioides has the enzymatic activity necessary to carry out the seventh step, the C-3 acetylation of isotrichodermol to form isotrichodermin. Together, the results of this study indicate that the Tri4 protein catalyzes the remaining four steps and is therefore a multifunctional monooxygenase required for trichothecene biosynthesis.
authors.affiliation: Mycotoxin Research Unit, United States Department of Agriculture-Agriculture Research Service (USDA-ARS), National Center for Agricultural Utilization Research, IL 61604-3902, USA. mccormsp@ncaur.usda.gov
authors.forename: Susan P
authors.initials: SP
authors.lastname: McCormick
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Alexander
authors.forename: Robert H
authors.initials: RH
authors.lastname: Proctor
mesh_terms: D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D005670:Fusarium / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal / Q000235:genetics; D006899:Mixed Function Oxygenases / Q000235:genetics; D009183:Mycotoxins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D014255:Trichothecenes / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D005656:Fungal Proteins; D009183:Mycotoxins; D014157:Transcription Factors; D014255:Trichothecenes; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases