P13513 · TRI5_FUSSP

Function

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:8593041, PubMed:9435078).
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:11352533, PubMed:12135578).
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).

Miscellaneous

Trichothecenes are sesquiterpenoid toxins that act by inhibiting protein biosynthesis.

Catalytic activity

Cofactor

Mg2+ (UniProtKB | Rhea| CHEBI:18420 )

Mn2+ (UniProtKB | Rhea| CHEBI:29035 )

Note: Some of the cofactor binding sites show unusual localization within the protein.

Activity regulation

Benzyl triethylammonium cation (BTAC) acts as a competitive inhibitor of trichodiene synthase reaction in the presence of pyrophosphate (PPi) (PubMed:17678871).

Kinetics

KM SUBSTRATE pH TEMPERATURE[C] NOTES EVIDENCE
62 nMfarnesyl pyrophosphate
78 nMMg2+
84.8 nMMn2+

pH Dependence

Optimum pH is 6.75-7.75.

Pathway

Sesquiterpene biosynthesis; trichothecene biosynthesis.

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site100Mg2+ 1 (UniProtKB | ChEBI)
Binding site164Mg2+ 1 (UniProtKB | ChEBI)
Binding site225Mg2+ 2 (UniProtKB | ChEBI)
Binding site229Mg2+ 2 (UniProtKB | ChEBI)
Binding site233Mg2+ 2 (UniProtKB | ChEBI)
Binding site239Mg2+ 3 (UniProtKB | ChEBI)
Binding site241Mg2+ 3 (UniProtKB | ChEBI)

GO annotations

AspectTerm
Molecular Functionmetal ion binding
Molecular Functiontrichodiene synthase activity
Biological Processsesquiterpenoid biosynthetic process

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Trichodiene synthase
  • EC number
  • Alternative names
    • Core trichothecene cluster (CTC) protein 5
    • Sesquiterpene cyclase TRI5
      (TS
      )

Gene names

    • Name
      TRI5
    • Synonyms
      TOX 5

Organism names

  • Taxonomic identifier
  • Strain
    • ATCC 24631 / NRRL 3299
  • Taxonomic lineage
    Eukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Sordariomycetes > Hypocreomycetidae > Hypocreales > Nectriaceae > Fusarium

Accessions

  • Primary accession
    P13513
  • Secondary accessions
    • Q7LP67

Phenotypes & Variants

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis100Does not significantly perturb the overall structure of trichodiene synthase but leads to an increased KM, a reduction in kcat, as well as to the production of anomalous sesquiterpene products in addition to trichodiene when incubated with farnesyl diphosphate.
Mutagenesis101Leads to an increased KM for Mg2+, a reduction in kcat, as well as to the production of anomalous sesquiterpene products in addition to trichodiene when incubated with farnesyl diphosphate.
Mutagenesis104Does not significantly affect the KM and kcat for farnesyl diphosphate.
Mutagenesis146Leads to the loss of activity.
Mutagenesis190Increases the KM for farnesyl diphosphate by about 1.3-fold and reduces the kcat by about 2000-fold.
Mutagenesis225Increases the KM for farnesyl diphosphate by about 6-fold and reduces the kcat by about 28-fold. Leads to complete loss of activity; when associated with S-229.
Mutagenesis229Increases the KM for farnesyl diphosphate by about 77-fold and reduces the kcat by about 9-fold. Leads to complete loss of activity; when associated with D-225.
Mutagenesis295Does not affect the catalytic activity.
Mutagenesis304Does not cause large changes in the overall structure but increases the KM for farnesyl diphosphate by about 25-fold, reduces the kcat by about 200-fold, and leads to conversion of farnesyl diphosphate not only to trichodiene but to at least 2 additional C15H24 hydrocarbons.
Mutagenesis305Does not cause large changes in the overall structure but increases the KM for farnesyl diphosphate by about 7-fold.
Mutagenesis305Increases the KM for farnesyl diphosphate by about 80-fold, reduces the kcat by about 120-fold, and leads to the conversion of farneyl diphosphate to an approximately equal mixture of trichodiene and an unidentified sesquiterpene hydrocarbon.

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00002215841-374Trichodiene synthase

Expression

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).

Family & Domains

Features

Showing features for region.

TypeIDPosition(s)Description
Region100-104Aspartate-rich domain

Sequence similarities

Belongs to the trichodiene synthase family.

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    374
  • Mass (Da)
    44,000
  • Last updated
    1990-01-01 v1
  • Checksum
    189E8FC1663C3763
MENFPTEYFLNTTVRLLEYIRYRDSNYTREERIENLHYAYNKAAHHFAQPRQQQLLKVDPKRLQASLQTIVGMVVYSWAKVSKECMADLSIHYTYTLVLDDSKDDPYPTMVNYFDDLQAGREQAHPWWALVNEHFPNVLRHFGPFCSLNLIRSTLDFFEGCWIEQYNFGGFPGSHDYPQFLRRMNGLGHCVGASLWPKEQFNERSLFLEITSAIAQMENWMVWVNDLMSFYKEFDDERDQISLVKNYVVSDEISLHEALEKLTQDTLHSSKQMVAVFSDKDPQVMDTIECFMHGYVTWHLCDRRYRLSEIYEKVKEEKTEDAQKFCKFYEQAANVGAVSPSEWAYPPVAQLANVRSKDVKEVQKPFLSSIELVE

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AF364179
EMBL· GenBank· DDBJ
AAD13657.1
EMBL· GenBank· DDBJ
Genomic DNA
AF359360
EMBL· GenBank· DDBJ
AAK33074.1
EMBL· GenBank· DDBJ
Genomic DNA
AY032745
EMBL· GenBank· DDBJ
AAK77935.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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