Identification and Functional Characterization of the Gene Cluster Responsible for Fusaproliferin Biosynthesis in Fusarium proliferatum. 2021

Asja Ćeranić, and Thomas Svoboda, and Franz Berthiller, and Michael Sulyok, and Jonathan Matthew Samson, and Ulrich Güldener, and Rainer Schuhmacher, and Gerhard Adam
Institute of Bioanalytics and Agro-Metabolomics, Department of Agrobiotechnology (IFA-Tulln), University of Natural Resources and Life Sciences, Vienna (BOKU), Konrad-Lorenz-Str. 20, 3430 Tulln, Austria.

The emerging mycotoxin fusaproliferin is produced by Fusarium proliferatum and other related Fusarium species. Several fungi from other taxonomic groups were also reported to produce fusaproliferin or the deacetylated derivative, known as siccanol or terpestacin. Here, we describe the identification and functional characterization of the Fusarium proliferatum genes encoding the fusaproliferin biosynthetic enzymes: a terpenoid synthase, two cytochrome P450s, a FAD-oxidase and an acetyltransferase. With the exception of one gene encoding a CYP450 (FUP2, FPRN_05484), knock-out mutants of the candidate genes could be generated, and the production of fusaproliferin and intermediates was tested by LC-MS/MS. Inactivation of the FUP1 (FPRN_05485) terpenoid synthase gene led to complete loss of fusaproliferin production. Disruption of a putative FAD-oxidase (FUP4, FPRN_05486) did not only affect oxidation of preterpestacin III to terpestacin, but also of new side products (11-oxo-preterpstacin and terpestacin aldehyde). In the knock-out strains lacking the predicted acetyltransferase (FUP5, FPRN_05487) fusaproliferin was no longer formed, but terpestacin was found at elevated levels. A model for the biosynthesis of fusaproliferin and of novel derivatives found in mutants is presented.

UI MeSH Term Description Entries
D009183 Mycotoxins Toxic compounds produced by FUNGI. Fungal Toxins,Mycotoxin,Toxins, Fungal
D002853 Chromatography, Liquid Chromatographic techniques in which the mobile phase is a liquid. Liquid Chromatography
D003313 Zea mays A plant species of the family POACEAE. It is a tall grass grown for its EDIBLE GRAIN, corn, used as food and animal FODDER. Corn,Indian Corn,Maize,Teosinte,Zea,Corn, Indian
D005670 Fusarium A mitosporic Hypocreales fungal genus, various species of which are important parasitic pathogens of plants and a variety of vertebrates. Teleomorphs include GIBBERELLA. Fusariums
D005810 Multigene Family A set of genes descended by duplication and variation from some ancestral gene. Such genes may be clustered together on the same chromosome or dispersed on different chromosomes. Examples of multigene families include those that encode the hemoglobins, immunoglobulins, histocompatibility antigens, actins, tubulins, keratins, collagens, heat shock proteins, salivary glue proteins, chorion proteins, cuticle proteins, yolk proteins, and phaseolins, as well as histones, ribosomal RNA, and transfer RNA genes. The latter three are examples of reiterated genes, where hundreds of identical genes are present in a tandem array. (King & Stanfield, A Dictionary of Genetics, 4th ed) Gene Clusters,Genes, Reiterated,Cluster, Gene,Clusters, Gene,Families, Multigene,Family, Multigene,Gene Cluster,Gene, Reiterated,Multigene Families,Reiterated Gene,Reiterated Genes
D001643 Bridged Bicyclo Compounds Saturated alicyclic hydrocarbon molecules consisting of two rings that have two non-adjacent atoms in common. Bicyclo Compounds,Bicyclo Compounds, Bridged
D013729 Terpenes A class of compounds composed of repeating 5-carbon units of HEMITERPENES. Isoprenoid,Terpene,Terpenoid,Isoprenoids,Terpenoids
D047630 Depsipeptides Compounds consisting of chains of AMINO ACIDS alternating with CARBOXYLIC ACIDS via ester and amide linkages. They are commonly cyclized. Cyclic Depsipeptide,Cyclodepsipeptide,Depsipeptide,Peptolide,Peptolides,Cryptophycins,Cyclodepsipeptides,Depsipeptides, Cyclic,Cyclic Depsipeptides,Depsipeptide, Cyclic
D053719 Tandem Mass Spectrometry A mass spectrometry technique using two (MS/MS) or more mass analyzers. With two in tandem, the precursor ions are mass-selected by a first mass analyzer, and focused into a collision region where they are then fragmented into product ions which are then characterized by a second mass analyzer. A variety of techniques are used to separate the compounds, ionize them, and introduce them to the first mass analyzer. For example, for in GC-MS/MS, GAS CHROMATOGRAPHY-MASS SPECTROMETRY is involved in separating relatively small compounds by GAS CHROMATOGRAPHY prior to injecting them into an ionization chamber for the mass selection. Mass Spectrometry-Mass Spectrometry,Mass Spectrometry Mass Spectrometry,Mass Spectrometry, Tandem
D037341 Fumonisins A group of MYCOTOXINS found in CORN contaminated with FUSARIUM fungus. They are chains of about 20 carbons with acidic ester, acetylamino and sometimes other substituents. They inhibit ceramide synthetase conversion of SPHINGOLIPIDS to CERAMIDES. Fumonisin

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