title: Two separate key enzymes and two pathway-specific transcription factors are involved in fusaric acid biosynthesis in Fusarium fujikuroi.
abstract: Fusaric acid (FSA) is a mycotoxin produced by several fusaria, including the rice pathogen Fusarium fujikuroi. Genes involved in FSA biosynthesis were previously identified as a cluster containing a polyketide synthase (PKS)-encoding (FUB1) and four additional genes (FUB2-FUB5). However, the biosynthetic steps leading to FSA as well as the origin of the nitrogen atom, which is incorporated into the polyketide backbone, remained unknown. In this study, seven additional cluster genes (FUB6-FUB12) were identified via manipulation of the global regulator FfSge1. The extended FUB gene cluster encodes two Zn(II)2 Cys6 transcription factors: Fub10 positively regulates expression of all FUB genes, whereas Fub12 is involved in the formation of the two FSA derivatives, i.e. dehydrofusaric acid and fusarinolic acid, serving as a detoxification mechanism. The major facilitator superfamily transporter Fub11 functions in the export of FSA out of the cell and is essential when FSA levels become critical. Next to Fub1, a second key enzyme was identified, the non-canonical non-ribosomal peptide synthetase Fub8. Chemical analyses of generated mutant strains allowed for the identification of a triketide as PKS product and the proposition of an FSA biosynthetic pathway, thereby unravelling the unique formation of a hybrid metabolite consisting of this triketide and an amino acid moiety.
authors.affiliation: Institute of Plant Biology and Biotechnology, Westfälische Wilhelms-University, Schlossplatz 8, 48143, Münster, Germany.
authors.forename: Lena
authors.initials: L
authors.lastname: Studt
authors.affiliation: Institute of Plant Biology and Biotechnology, Westfälische Wilhelms-University, Schlossplatz 8, 48143, Münster, Germany.
authors.forename: Slavica
authors.initials: S
authors.lastname: Janevska
authors.affiliation: Institute of Plant Biology and Biotechnology, Westfälische Wilhelms-University, Schlossplatz 8, 48143, Münster, Germany.
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Niehaus
authors.affiliation: Kekulé Institute for Organic Chemistry and Biochemistry, Rheinische Friedrich-Wilhelms-University Bonn, 53121, Bonn, Germany.
authors.forename: Immo
authors.initials: I
authors.lastname: Burkhardt
authors.affiliation: Institute of Food Chemistry, Westfälische Wilhelms-University, Corrensstr. 45, 48149, Münster, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Arndt
authors.affiliation: Lawrence Berkeley National Lab, DOE Joint Genome Institute, 2800 Mitchell Drive, Walnut Creek, CA, 94598, USA.
authors.forename: Christian M K
authors.initials: CM
authors.lastname: Sieber
authors.affiliation: Institute of Food Chemistry, Westfälische Wilhelms-University, Corrensstr. 45, 48149, Münster, Germany.
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Humpf
authors.affiliation: Kekulé Institute for Organic Chemistry and Biochemistry, Rheinische Friedrich-Wilhelms-University Bonn, 53121, Bonn, Germany.
authors.forename: Jeroen S
authors.initials: JS
authors.lastname: Dickschat
authors.affiliation: Institute of Plant Biology and Biotechnology, Westfälische Wilhelms-University, Schlossplatz 8, 48143, Münster, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Tudzynski
mesh_terms: D001692:Biological Transport / Q000235:genetics*; D053898:Biosynthetic Pathways / Q000235:genetics*; D005669:Fusaric Acid / Q000031:analogs & derivatives / Q000096:biosynthesis* / Q000235:genetics; D005670:Fusarium / Q000201:enzymology* / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics; D012275:Oryza / Q000235:genetics; D048630:Polyketide Synthases / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
chemical_list: D014157:Transcription Factors; C430858:fusarinolic acid; D048630:Polyketide Synthases; D005669:Fusaric Acid