title: Gibepyrone Biosynthesis in the Rice Pathogen Fusarium fujikuroi Is Facilitated by a Small Polyketide Synthase Gene Cluster.
abstract: The 2H-pyran-2-one gibepyrone A and its oxidized derivatives gibepyrones B-F have been isolated from the rice pathogenic fungus Fusarium fujikuroi already more than 20 years ago. However, these products have not been linked to the respective biosynthetic genes, and therefore, their biosynthesis has not yet been analyzed on a molecular level. Feeding experiments with isotopically labeled precursors clearly supported a polyketide origin for the formal monoterpenoid gibepyrone A, whereas the terpenoid pathway could be excluded. Targeted gene deletion verified that the F. fujikuroi polyketide synthase PKS13, designated Gpy1, is responsible for gibepyrone A biosynthesis. Next to Gpy1, the ATP-binding cassette transporter Gpy2 is encoded by the gibepyrone gene cluster. Gpy2 was shown to have only a minor impact on the actual efflux of gibepyrone A out of the cell. Instead, we obtained evidence that Gpy2 is involved in gene regulation as it represses GPY1 gene expression. Thus, GPY1 was up-regulated and gibepyrone A production was enhanced both extra- and intracellularly in Δgpy2 mutants. Furthermore, expression of GPY genes is strictly repressed by members of the fungus-specific velvet complex, Vel1, Vel2, and Lae1, whereas Sge1, a major regulator of secondary metabolism in F. fujikuroi, affects gibepyrone biosynthesis in a positive manner. The gibepyrone A derivatives gibepyrones B and D were shown to be produced by cluster-independent P450 monooxygenases, probably to protect the fungus from the toxic product. In contrast, the formation of gibepyrones E and F from gibepyrone A is a spontaneous process and independent of enzymatic activity.
authors.affiliation: From the Institut für Biologie und Biotechnologie der Pflanzen, Westfälische Wilhelms-Universität Münster, Schlossplatz 8, D-48143 Münster.
authors.forename: Slavica
authors.initials: S
authors.lastname: Janevska
authors.affiliation: the Institut für Lebensmittelchemie, Westfälische Wilhelms-Universität Münster, Corrensstrasse 45, D-48149 Münster, and.
authors.forename: Birgit
authors.initials: B
authors.lastname: Arndt
authors.affiliation: From the Institut für Biologie und Biotechnologie der Pflanzen, Westfälische Wilhelms-Universität Münster, Schlossplatz 8, D-48143 Münster.
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Niehaus
authors.affiliation: the Kekulé-Institut für Organische Chemie und Biochemie, Rheinische Friedrich Wilhelms-Universität Bonn, Gerhard-Domagk-Strasse 1, D-53121 Bonn, Germany.
authors.forename: Immo
authors.initials: I
authors.lastname: Burkhardt
authors.affiliation: From the Institut für Biologie und Biotechnologie der Pflanzen, Westfälische Wilhelms-Universität Münster, Schlossplatz 8, D-48143 Münster.|the Institut für Lebensmittelchemie, Westfälische Wilhelms-Universität Münster, Corrensstrasse 45, D-48149 Münster, and.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Rösler
authors.affiliation: the Kekulé-Institut für Organische Chemie und Biochemie, Rheinische Friedrich Wilhelms-Universität Bonn, Gerhard-Domagk-Strasse 1, D-53121 Bonn, Germany.
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Brock
authors.affiliation: the Institut für Lebensmittelchemie, Westfälische Wilhelms-Universität Münster, Corrensstrasse 45, D-48149 Münster, and.
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Humpf
authors.affiliation: the Kekulé-Institut für Organische Chemie und Biochemie, Rheinische Friedrich Wilhelms-Universität Bonn, Gerhard-Domagk-Strasse 1, D-53121 Bonn, Germany dickschat@uni-bonn.de.
authors.forename: Jeroen S
authors.initials: JS
authors.lastname: Dickschat
authors.affiliation: From the Institut für Biologie und Biotechnologie der Pflanzen, Westfälische Wilhelms-Universität Münster, Schlossplatz 8, D-48143 Münster, tudzynsb@uni-muenster.de.
authors.forename: Bettina
authors.initials: B
authors.lastname: Tudzynski
mesh_terms: D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D005670:Fusarium / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D005810:Multigene Family; D012275:Oryza / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology; D010935:Plant Diseases / Q000235:genetics* / Q000382:microbiology; D048630:Polyketide Synthases / Q000378:metabolism*; D011753:Pyrones / Q000378:metabolism*
chemical_list: D005656:Fungal Proteins; D011753:Pyrones; D048630:Polyketide Synthases
keywords: Fusarium fujikuroi; biosynthesis; fungi; gene regulation; gibepyrones; polyketide; secondary metabolism