UniProt functional annotation for P13513



	UniProt functional annotation for P13513

UniProt code: P13513.

Organism: Fusarium sporotrichioides.

Taxonomy: Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes; Hypocreomycetidae; Hypocreales; Nectriaceae; Fusarium.

Function: Trichodiene synthase; part of the core gene cluster that mediates the biosynthesis of trichothecenes, a very large family of chemically related bicyclic sesquiterpene compounds acting as mycotoxins, including T2-toxin (PubMed:11352533, PubMed:2817906). The biosynthesis of trichothecenes begins with the cyclization of farnesyl diphosphate to trichodiene and is catalyzed by the trichodiene synthase TRI5 (PubMed:3800398, PubMed:7873527, PubMed:8823172). Trichodiene undergoes a series of oxygenations catalyzed by the cytochrome P450 monooxygenase TRI4 (PubMed:7651333). TRI4 controls the addition of four oxygens at C-2, C-3, C-11, and the C-12, C-13-epoxide to form the intermediate isotrichotriol (PubMed:16917519). Isotrichotriol then undergoes a non-enzymatic isomerization and cyclization to form isotrichodermol (PubMed:2317042). During this process, the oxygen at the C-2 position becomes the pyran ring oxygen and the hydroxyl group at C-11 is lost (PubMed:2317042). More complex type A trichothecenes are built by modifying isotrichodermol through a series of paired hydroxylation and acetylation or acylation steps (PubMed:11352533). Isotrichodermol is converted to isotrichodermin by the acetyltransferase TRI101 (PubMed:10583973). TRI101 encodes a C-3 transacetylase that acts as a self-protection or resistance factor during biosynthesis and that the presence of a free C-3 hydroxyl group is a key component of Fusarium trichothecene phytotoxicity (PubMed:10583973). A second hydroxyl group is added to C-15 by the trichothecene C-15 hydroxylase TRI11, producing 15-decalonectrin, which is then acetylated by TRI3, producing calonectrin (PubMed:9435078, PubMed:8593041). A third hydroxyl group is added at C-4 by the cytochrome P450 monooxygenase TRI13, converting calonectrin to 3,15- diacetoxyspirpenol, which is subsequently acetylated by the acetyltransferase TRI7 (PubMed:12135578, PubMed:11352533). A fourth hydroxyl group is added to C-8 by the cytochrome P450 monooxygenase TRI1, followed by the addition of an isovaleryl moiety by TRI16 (PubMed:12620849, PubMed:14532047). Finally, the acetyl group is removed from the C-3 position by the trichothecene C-3 esterase TRI8 to produce T-2 toxin (PubMed:12039755). {ECO:0000269|PubMed:10583973, ECO:0000269|PubMed:11352533, ECO:0000269|PubMed:12039755, ECO:0000269|PubMed:12135578, ECO:0000269|PubMed:12620849, ECO:0000269|PubMed:14532047, ECO:0000269|PubMed:16917519, ECO:0000269|PubMed:2317042, ECO:0000269|PubMed:3800398, ECO:0000269|PubMed:7651333, ECO:0000269|PubMed:8593041, ECO:0000269|PubMed:9435078}.

Catalytic activity: Reaction=(2E,6E)-farnesyl diphosphate = diphosphate + trichodiene; Xref=Rhea:RHEA:12052, ChEBI:CHEBI:15861, ChEBI:CHEBI:33019, ChEBI:CHEBI:175763; EC=4.2.3.6; Evidence={ECO:0000269|PubMed:16171386, ECO:0000269|PubMed:17678871, ECO:0000269|PubMed:3800398, ECO:0000269|PubMed:7873527, ECO:0000269|PubMed:8823172};

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:15835903, ECO:0000269|PubMed:16171386, ECO:0000269|PubMed:17678871, ECO:0000269|PubMed:17996718, ECO:0000269|PubMed:3800398, ECO:0000269|PubMed:8823172}; Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000269|PubMed:8823172}; Note=Some of the cofactor binding sites show unusual localization within the protein. {ECO:0000305};

Activity regulation: Benzyl triethylammonium cation (BTAC) acts as a competitive inhibitor of trichodiene synthase reaction in the presence of pyrophospahte (PPi) (PubMed:17678871). {ECO:0000269|PubMed:17678871}.

Biophysicochemical properties: Kinetic parameters: KM=62.0 nM for farnesyl pyrophosphate {ECO:0000269|PubMed:3800398, ECO:0000269|PubMed:7873527}; KM=78.0 nM for Mg(2+) {ECO:0000269|PubMed:8823172}; KM=84.8 nM for Mn(2+) {ECO:0000269|PubMed:8823172}; pH dependence: Optimum pH is 6.75-7.75. {ECO:0000269|PubMed:3800398};

Pathway: Sesquiterpene biosynthesis; trichothecene biosynthesis. {ECO:0000269|PubMed:3800398}.

Induction: Expression is positively regulated by the trichothecene cluster-specific transcription activator TRI10 (PubMed:12732543). Expression is induced between 18h and 21h growth on GYEP medium (PubMed:16347944). The initial detection of trichothecenes occurs several hours after the initial detection of TRI5 (PubMed:16347944). The initiation of trichothecene biosynthesis occurs with a high concentration of glucose remaining in the culture medium (PubMed:16347944). {ECO:0000269|PubMed:12732543, ECO:0000269|PubMed:16347944}.

Miscellaneous: Trichothecenes are sesquiterpenoid toxins that act by inhibiting protein biosynthesis. {ECO:0000305}.

Similarity: Belongs to the trichodiene synthase family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Fusarium sporotrichioides.
Taxonomy:		Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes; Hypocreomycetidae; Hypocreales; Nectriaceae; Fusarium.



Function:		Trichodiene synthase; part of the core gene cluster that mediates the biosynthesis of trichothecenes, a very large family of chemically related bicyclic sesquiterpene compounds acting as mycotoxins, including T2-toxin (PubMed:11352533, PubMed:2817906). The biosynthesis of trichothecenes begins with the cyclization of farnesyl diphosphate to trichodiene and is catalyzed by the trichodiene synthase TRI5 (PubMed:3800398, PubMed:7873527, PubMed:8823172). Trichodiene undergoes a series of oxygenations catalyzed by the cytochrome P450 monooxygenase TRI4 (PubMed:7651333). TRI4 controls the addition of four oxygens at C-2, C-3, C-11, and the C-12, C-13-epoxide to form the intermediate isotrichotriol (PubMed:16917519). Isotrichotriol then undergoes a non-enzymatic isomerization and cyclization to form isotrichodermol (PubMed:2317042). During this process, the oxygen at the C-2 position becomes the pyran ring oxygen and the hydroxyl group at C-11 is lost (PubMed:2317042). More complex type A trichothecenes are built by modifying isotrichodermol through a series of paired hydroxylation and acetylation or acylation steps (PubMed:11352533). Isotrichodermol is converted to isotrichodermin by the acetyltransferase TRI101 (PubMed:10583973). TRI101 encodes a C-3 transacetylase that acts as a self-protection or resistance factor during biosynthesis and that the presence of a free C-3 hydroxyl group is a key component of Fusarium trichothecene phytotoxicity (PubMed:10583973). A second hydroxyl group is added to C-15 by the trichothecene C-15 hydroxylase TRI11, producing 15-decalonectrin, which is then acetylated by TRI3, producing calonectrin (PubMed:9435078, PubMed:8593041). A third hydroxyl group is added at C-4 by the cytochrome P450 monooxygenase TRI13, converting calonectrin to 3,15- diacetoxyspirpenol, which is subsequently acetylated by the acetyltransferase TRI7 (PubMed:12135578, PubMed:11352533). A fourth hydroxyl group is added to C-8 by the cytochrome P450 monooxygenase TRI1, followed by the addition of an isovaleryl moiety by TRI16 (PubMed:12620849, PubMed:14532047). Finally, the acetyl group is removed from the C-3 position by the trichothecene C-3 esterase TRI8 to produce T-2 toxin (PubMed:12039755). {ECO:0000269\|PubMed:10583973, ECO:0000269\|PubMed:11352533, ECO:0000269\|PubMed:12039755, ECO:0000269\|PubMed:12135578, ECO:0000269\|PubMed:12620849, ECO:0000269\|PubMed:14532047, ECO:0000269\|PubMed:16917519, ECO:0000269\|PubMed:2317042, ECO:0000269\|PubMed:3800398, ECO:0000269\|PubMed:7651333, ECO:0000269\|PubMed:8593041, ECO:0000269\|PubMed:9435078}.


Catalytic activity:		Reaction=(2E,6E)-farnesyl diphosphate = diphosphate + trichodiene; Xref=Rhea:RHEA:12052, ChEBI:CHEBI:15861, ChEBI:CHEBI:33019, ChEBI:CHEBI:175763; EC=4.2.3.6; Evidence={ECO:0000269\|PubMed:16171386, ECO:0000269\|PubMed:17678871, ECO:0000269\|PubMed:3800398, ECO:0000269\|PubMed:7873527, ECO:0000269\|PubMed:8823172};
Cofactor:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269\|PubMed:15835903, ECO:0000269\|PubMed:16171386, ECO:0000269\|PubMed:17678871, ECO:0000269\|PubMed:17996718, ECO:0000269\|PubMed:3800398, ECO:0000269\|PubMed:8823172}; Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000269\|PubMed:8823172}; Note=Some of the cofactor binding sites show unusual localization within the protein. {ECO:0000305};
Activity regulation:		Benzyl triethylammonium cation (BTAC) acts as a competitive inhibitor of trichodiene synthase reaction in the presence of pyrophospahte (PPi) (PubMed:17678871). {ECO:0000269\|PubMed:17678871}.
Biophysicochemical properties:		Kinetic parameters: KM=62.0 nM for farnesyl pyrophosphate {ECO:0000269\|PubMed:3800398, ECO:0000269\|PubMed:7873527}; KM=78.0 nM for Mg(2+) {ECO:0000269\|PubMed:8823172}; KM=84.8 nM for Mn(2+) {ECO:0000269\|PubMed:8823172}; pH dependence: Optimum pH is 6.75-7.75. {ECO:0000269\|PubMed:3800398};
Pathway:		Sesquiterpene biosynthesis; trichothecene biosynthesis. {ECO:0000269\|PubMed:3800398}.
Induction:		Expression is positively regulated by the trichothecene cluster-specific transcription activator TRI10 (PubMed:12732543). Expression is induced between 18h and 21h growth on GYEP medium (PubMed:16347944). The initial detection of trichothecenes occurs several hours after the initial detection of TRI5 (PubMed:16347944). The initiation of trichothecene biosynthesis occurs with a high concentration of glucose remaining in the culture medium (PubMed:16347944). {ECO:0000269\|PubMed:12732543, ECO:0000269\|PubMed:16347944}.
Miscellaneous:		Trichothecenes are sesquiterpenoid toxins that act by inhibiting protein biosynthesis. {ECO:0000305}.
Similarity:		Belongs to the trichodiene synthase family. {ECO:0000305}.