CTB3_CERBT
ID CTB3_CERBT Reviewed; 871 AA.
AC A0A2G5IC53;
DT 17-JUN-2020, integrated into UniProtKB/Swiss-Prot.
DT 31-JAN-2018, sequence version 1.
DT 03-AUG-2022, entry version 16.
DE RecName: Full=Dual O-methyltransferase/FAD-dependent monooxygenase CTB3 {ECO:0000303|PubMed:29844193};
DE AltName: Full=Cercosporin toxin biosynthesis cluster protein 3 {ECO:0000303|PubMed:29844193};
DE Includes:
DE RecName: Full=O-methyltransferase {ECO:0000250|UniProtKB:Q2I0M6};
DE EC=2.1.1.- {ECO:0000250|UniProtKB:Q2I0M6};
DE Includes:
DE RecName: Full=FAD-dependent monooxygenase {ECO:0000250|UniProtKB:Q2I0M6};
DE EC=1.-.-.- {ECO:0000250|UniProtKB:Q2I0M6};
GN Name=CTB3 {ECO:0000303|PubMed:29844193}; ORFNames=CB0940_00834;
OS Cercospora beticola (Sugarbeet leaf spot fungus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Dothideomycetes;
OC Dothideomycetidae; Mycosphaerellales; Mycosphaerellaceae; Cercospora.
OX NCBI_TaxID=122368;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], FUNCTION, AND PATHWAY.
RC STRAIN=09-40;
RX PubMed=29844193; DOI=10.1073/pnas.1712798115;
RA de Jonge R., Ebert M.K., Huitt-Roehl C.R., Pal P., Suttle J.C.,
RA Spanner R.E., Neubauer J.D., Jurick W.M. II, Stott K.A., Secor G.A.,
RA Thomma B.P.H.J., Van de Peer Y., Townsend C.A., Bolton M.D.;
RT "Gene cluster conservation provides insight into cercosporin biosynthesis
RT and extends production to the genus Colletotrichum.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:E5459-E5466(2018).
RN [2]
RP REVIEW ON CERCOSPORIN.
RX PubMed=11701851; DOI=10.1146/annurev.phyto.38.1.461;
RA Daub M.E., Ehrenshaft M.;
RT "The photoactivated cercospora toxin cercosporin: contributions to plant
RT disease and fundamental biology.";
RL Annu. Rev. Phytopathol. 38:461-490(2000).
CC -!- FUNCTION: Dual O-methyltransferase/FAD-dependent monooxygenase; part of
CC the gene cluster that mediates the biosynthesis of cercosporin, a
CC light-activated, non-host-selective toxin (By similarity). The
CC perylenequinone chromophore of cercosporin absorbs light energy to
CC attain an electronically-activated triplet state and produces active
CC oxygen species such as the hydroxyl radical, superoxide, hydrogen
CC peroxide or singlet oxygen upon reaction with oxygen molecules
CC (PubMed:11701851). These reactive oxygen species cause damage to
CC various cellular components including lipids, proteins and nucleic
CC acids (PubMed:11701851). The first step of cercosporin biosynthesis is
CC performed by the polyketide synthase CTB1 which catalyzes the formation
CC of nor-toralactone (By similarity). The starter unit acyltransferase
CC (SAT) domain of CTB1 initiates polyketide extension by the selective
CC utilization of acetyl-CoA, which is elongated to the heptaketide in the
CC beta-ketoacyl synthase (KS) domain by successive condensations with six
CC malonyl units introduced by the malonyl acyltransferase (MAT) domain.
CC The product template (PT) domain catalyzes C4-C9 and C2-C11 aldol
CC cyclizations and dehydrations to a trihydroxynaphthalene, which is
CC thought to be delivered to the thioesterase (TE) domain for product
CC release (By similarity). The bifunctional enzyme CTB3 then methylates
CC nor-toralactone to toralactone before conducting an unusual oxidative
CC aromatic ring opening (By similarity). The O-methyltransferase CTB2
CC further methylates the nascent OH-6 of the CBT3 product, blocking
CC further oxidation at this site before the reductase CTB6 reduces the 2-
CC oxopropyl ketone at position C7, giving naphthalene (By similarity).
CC The FAD-dependent monooxygenase CTB5 in concert with the multicopper
CC oxidase CTB12 are responsible for homodimerization of naphthalene with
CC CTB7 installing the dioxepine moiety, finally producing cercosporin (By
CC similarity). The fasciclin domain-containing protein CTB11 might act
CC with CTB5 and CTB12 whereas the roles of CTB9 and CTB10 have still to
CC be elucidated (By similarity). {ECO:0000250|UniProtKB:Q0UHZ9,
CC ECO:0000250|UniProtKB:Q2I0M6, ECO:0000303|PubMed:11701851}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=nor-toralactone + S-adenosyl-L-methionine = H(+) + S-adenosyl-
CC L-homocysteine + toralactone; Xref=Rhea:RHEA:62908,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:78029, ChEBI:CHEBI:146018;
CC Evidence={ECO:0000250|UniProtKB:Q2I0M6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62909;
CC Evidence={ECO:0000250|UniProtKB:Q2I0M6};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + NADH + O2 + toralactone = 1-(3,4,5-trihydroxy-7-
CC methoxynaphthalen-2-yl)propan-2-one + CO2 + NAD(+);
CC Xref=Rhea:RHEA:62912, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:78029, ChEBI:CHEBI:146020;
CC Evidence={ECO:0000250|UniProtKB:Q2I0M6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62913;
CC Evidence={ECO:0000250|UniProtKB:Q2I0M6};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000250|UniProtKB:Q2I0M6}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the paxM FAD-
CC dependent monooxygenase family. {ECO:0000305}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the class I-like SAM-
CC binding methyltransferase superfamily. Cation-independent O-
CC methyltransferase family. COMT subfamily. {ECO:0000305}.
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DR EMBL; LKMD01000100; PIB02398.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A2G5IC53; -.
DR SMR; A0A2G5IC53; -.
DR OrthoDB; 817726at2759; -.
DR Proteomes; UP000230605; Chromosome 1.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0008171; F:O-methyltransferase activity; IEA:InterPro.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR016461; COMT-like.
DR InterPro; IPR002938; FAD-bd.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR001077; O_MeTrfase_dom.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF01494; FAD_binding_3; 1.
DR Pfam; PF00891; Methyltransf_2; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS51683; SAM_OMT_II; 1.
PE 3: Inferred from homology;
KW FAD; Flavoprotein; Methyltransferase; Monooxygenase;
KW Multifunctional enzyme; NAD; Oxidoreductase; S-adenosyl-L-methionine;
KW Transferase.
FT CHAIN 1..871
FT /note="Dual O-methyltransferase/FAD-dependent monooxygenase
FT CTB3"
FT /id="PRO_0000449856"
FT REGION 1..429
FT /note="O-methyltransferase"
FT /evidence="ECO:0000250|UniProtKB:Q2I0M6"
FT REGION 430..871
FT /note="FAD-dependent monooxygenase"
FT /evidence="ECO:0000250|UniProtKB:Q2I0M6"
FT ACT_SITE 331
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01020"
FT BINDING 279
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01020"
FT BINDING 485..488
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 617
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 627..631
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 681..683
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 774..782
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
SQ SEQUENCE 871 AA; 95852 MW; 4292C85D124F9F0B CRC64;
MMQFQRDLEA SLEAVSANAQ ELLKSLKSRK DVQDLNASLP KDPLDNCDAQ TQAARAQLAE
AATRILRLSI RPQEYLEHLQ NGYQHLTCFR WLVELNILDH LPHSGTISYT DLARKASVPP
MQLRSICRMA ICNGFLEEPE ANQVRHSRIS ALFARDESYL GWARWMVNYS VPAAYKLSDA
TRSWGETVAK DQTAFNLGMD VKVPFFDHLR QTPAMKDAFA AYMRNVTSNA TWGLQHAVTG
FDWASLPRGA KVVDVGGSLG HGSIAIAKEH THLTFVIQDL PETVAGARKE MAQNDKIEAS
VKSRITFQEH DFFGPQTVKD ADVYFLRMIC HDWPDNEAKV ILSQIRAALK PGAQIVIMDT
ILPQPGTTSV LQEQQLRIRD LTMMEVFNAK ERELEDWSSL MQSAGLEISR VNQPLNSVMG
LLTVRSAGQT ALSGTNTLTP ELVTAVSAST GSADSRPVLI AGAGIAGLCL AQALKKAGID
FRVFERDSHI DARPQGYRLK FEADAAQSLK NILPDDVYEA FELSNAVTAV GETDFNPFNG
NIIHSRTGGG LSGKKGLYAT FTVDRKAFRT QLMTGIEDKI SFGKEIAYYK TDDSASTVTA
EFKDGTHVTG SFLAGTDGLH SVVRKTCVPD HRIVDTGAAC IYGKTVMTPE FLARFPEKGL
RFMTVVSDIA PMLQSCLIGD SPVTLLLEPI RFSEASRARY PELPADYVYW ALIGPKERFG
SQEVTSMKNF VSLDQAAEQA AKLSLAVTEE WHPSLRALFE LQDTKQASLI RVASTIPDIP
SWESHSNVTV LGDSIHPMSP CGGVGANTAI VDADALAKVL VEHGTKPPVN AIAEFEAAMR
TRAKRNIWRS EVGSKRMFGQ KNLVDCSEFV F
