Q2I0M6 · CTB3_CERNC
- ProteinDual O-methyltransferase/FAD-dependent monooxygenase CTB3
- GeneCTB3
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids871 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score4/5
Function
function
Dual O-methyltransferase/FAD-dependent monooxygenase; part of the gene cluster that mediates the biosynthesis of cercosporin, a light-activated, non-host-selective toxin (PubMed:15915645, PubMed:17074519, PubMed:26938470).
The perylenequinone chromophore of cercosporin absorbs light energy to attain an electronically-activated triplet state and produces active oxygen species such as the hydroxyl radical, superoxide, hydrogen peroxide or singlet oxygen upon reaction with oxygen molecules (PubMed:11701851).
These reactive oxygen species cause damage to various cellular components including lipids, proteins and nucleic acids (PubMed:11701851).
The first step of cercosporin biosynthesis is performed by the polyketide synthase CTB1 which catalyzes the formation of nor-toralactone (PubMed:23108075, PubMed:26938470).
The starter unit acyltransferase (SAT) domain of CTB1 initiates polyketide extension by the selective utilization of acetyl-CoA, which is elongated to the heptaketide in the beta-ketoacyl synthase (KS) domain by successive condensations with six malonyl units introduced by the malonyl acyltransferase (MAT) domain. The product template (PT) domain catalyzes C4-C9 and C2-C11 aldol cyclizations and dehydrations to a trihydroxynaphthalene, which is thought to be delivered to the thioesterase (TE) domain for product release (PubMed:23108075).
The bifunctional enzyme CTB3 then methylates nor-toralactone to toralactone before conducting an unusual oxidative aromatic ring opening (PubMed:17074519, PubMed:26938470).
The O-methyltransferase CTB2 further methylates the nascent OH-6 of the CBT3 product, blocking further oxidation at this site before the reductase CTB6 reduces the 2-oxopropyl ketone at position C7, giving naphthalene (PubMed:17660442, PubMed:26938470).
The FAD-dependent monooxygenase CTB5 in concert with the multicopper oxidase CTB12 are responsible for homodimerization of naphthalene with CTB7 installing the dioxepine moiety, finally producing cercosporin (PubMed:17660442, PubMed:26938470, PubMed:30809363).
The fasciclin domain-containing protein CTB11 might act with CTB5 and CTB12 whereas the roles of CTB9 and CTB10 have still to be elucidated (By similarity).
The perylenequinone chromophore of cercosporin absorbs light energy to attain an electronically-activated triplet state and produces active oxygen species such as the hydroxyl radical, superoxide, hydrogen peroxide or singlet oxygen upon reaction with oxygen molecules (PubMed:11701851).
These reactive oxygen species cause damage to various cellular components including lipids, proteins and nucleic acids (PubMed:11701851).
The first step of cercosporin biosynthesis is performed by the polyketide synthase CTB1 which catalyzes the formation of nor-toralactone (PubMed:23108075, PubMed:26938470).
The starter unit acyltransferase (SAT) domain of CTB1 initiates polyketide extension by the selective utilization of acetyl-CoA, which is elongated to the heptaketide in the beta-ketoacyl synthase (KS) domain by successive condensations with six malonyl units introduced by the malonyl acyltransferase (MAT) domain. The product template (PT) domain catalyzes C4-C9 and C2-C11 aldol cyclizations and dehydrations to a trihydroxynaphthalene, which is thought to be delivered to the thioesterase (TE) domain for product release (PubMed:23108075).
The bifunctional enzyme CTB3 then methylates nor-toralactone to toralactone before conducting an unusual oxidative aromatic ring opening (PubMed:17074519, PubMed:26938470).
The O-methyltransferase CTB2 further methylates the nascent OH-6 of the CBT3 product, blocking further oxidation at this site before the reductase CTB6 reduces the 2-oxopropyl ketone at position C7, giving naphthalene (PubMed:17660442, PubMed:26938470).
The FAD-dependent monooxygenase CTB5 in concert with the multicopper oxidase CTB12 are responsible for homodimerization of naphthalene with CTB7 installing the dioxepine moiety, finally producing cercosporin (PubMed:17660442, PubMed:26938470, PubMed:30809363).
The fasciclin domain-containing protein CTB11 might act with CTB5 and CTB12 whereas the roles of CTB9 and CTB10 have still to be elucidated (By similarity).
Catalytic activity
- nor-toralactone + S-adenosyl-L-methionine = toralactone + S-adenosyl-L-homocysteine + H+This reaction proceeds in the forward direction.
- toralactone + NADH + O2 + H+ = 1-(3,4,5-trihydroxy-7-methoxynaphthalen-2-yl)propan-2-one + CO2 + NAD+This reaction proceeds in the forward direction.
Pathway
Mycotoxin biosynthesis.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Binding site | 279 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | |||
Active site | 331 | Proton acceptor | |||
Binding site | 485 | FAD (UniProtKB | ChEBI) | |||
Binding site | 569 | FAD (UniProtKB | ChEBI) | |||
Binding site | 806 | FAD (UniProtKB | ChEBI) | |||
GO annotations
Aspect | Term | |
---|---|---|
Molecular Function | monooxygenase activity | |
Molecular Function | O-methyltransferase activity | |
Biological Process | biosynthetic process | |
Biological Process | methylation |
Keywords
- Molecular function
- Ligand
Names & Taxonomy
Protein names
- Recommended nameDual O-methyltransferase/FAD-dependent monooxygenase CTB3
- Alternative names
Including 2 domains:
- Recommended nameO-methyltransferase
- EC number
- Recommended nameFAD-dependent monooxygenase
- EC number
Gene names
Organism names
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Dothideomycetes > Dothideomycetidae > Mycosphaerellales > Mycosphaerellaceae > Cercospora
Accessions
- Primary accessionQ2I0M6
Phenotypes & Variants
Disruption phenotype
Abolishes the production of cercosporin but accumulates the naphthopyrones nor-toralactone and toralactone, as well as the oxidation product of nor-toralactone, naphthoquinone (PubMed:17074519, PubMed:26938470).
Adopts a dark yellow-brown coloration, with slight export of pigmented metabolites into the agar (PubMed:26938470).
Adopts a dark yellow-brown coloration, with slight export of pigmented metabolites into the agar (PubMed:26938470).
Miscellaneous
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Chain | PRO_0000444967 | 1-871 | Dual O-methyltransferase/FAD-dependent monooxygenase CTB3 | ||
Expression
Induction
Expression is positively regulated by the cercosporin cluster-specific transcription factor CTB8 (PubMed:17462021).
Expression is also affected by nitrogen and carbon sources and pH, and is also controlled by another transcription activator, CRG1, previously shown to regulate cercosporin production and resistance (PubMed:17462021).
Expression is also affected by nitrogen and carbon sources and pH, and is also controlled by another transcription activator, CRG1, previously shown to regulate cercosporin production and resistance (PubMed:17462021).
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Region | 1-429 | O-methyltransferase | |||
Region | 430-871 | FAD-dependent monooxygenase | |||
Sequence similarities
In the C-terminal section; belongs to the paxM FAD-dependent monooxygenase family.
In the N-terminal section; belongs to the class I-like SAM-binding methyltransferase superfamily. Cation-independent O-methyltransferase family. COMT subfamily.
Family and domain databases
Sequence
- Sequence statusComplete
- Length871
- Mass (Da)95,728
- Last updated2006-05-02 v2
- Checksum7F7DD803CE5EE066
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
DQ355149 EMBL· GenBank· DDBJ | ABC79591.2 EMBL· GenBank· DDBJ | Genomic DNA |