STHD_PHANO
ID STHD_PHANO Reviewed; 475 AA.
AC Q0UK51;
DT 11-DEC-2019, integrated into UniProtKB/Swiss-Prot.
DT 05-SEP-2006, sequence version 1.
DT 03-AUG-2022, entry version 77.
DE RecName: Full=Cytochrome P450 monooxygenase sthD {ECO:0000303|PubMed:31553484};
DE EC=1.-.-.- {ECO:0000305|PubMed:31553484};
DE AltName: Full=Stemphyloxin II biosynthesis cluster protein D {ECO:0000303|PubMed:31553484};
DE Flags: Precursor;
GN Name=sthD {ECO:0000303|PubMed:31553484}; ORFNames=SNOG_07863;
OS Phaeosphaeria nodorum (strain SN15 / ATCC MYA-4574 / FGSC 10173) (Glume
OS blotch fungus) (Parastagonospora nodorum).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Dothideomycetes;
OC Pleosporomycetidae; Pleosporales; Pleosporineae; Phaeosphaeriaceae;
OC Parastagonospora.
OX NCBI_TaxID=321614;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=SN15 / ATCC MYA-4574 / FGSC 10173;
RX PubMed=18024570; DOI=10.1105/tpc.107.052829;
RA Hane J.K., Lowe R.G.T., Solomon P.S., Tan K.-C., Schoch C.L.,
RA Spatafora J.W., Crous P.W., Kodira C.D., Birren B.W., Galagan J.E.,
RA Torriani S.F.F., McDonald B.A., Oliver R.P.;
RT "Dothideomycete-plant interactions illuminated by genome sequencing and EST
RT analysis of the wheat pathogen Stagonospora nodorum.";
RL Plant Cell 19:3347-3368(2007).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=31553484; DOI=10.1002/chem.201904360;
RA Li H., Hu J., Wei H., Solomon P.S., Stubbs K.A., Chooi Y.H.;
RT "Biosynthesis of a Tricyclo[6.2.2.02,7]dodecane System by a Berberine
RT Bridge Enzyme-like Intramolecular Aldolase.";
RL Chemistry 25:15062-15066(2019).
CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of the phytotoxin stemphyloxin II
CC (PubMed:31553484). The first step of the pathway is the synthesis of
CC dehydroprobetaenone I by the polyketide synthase sthA and the enoyl
CC reductase sthE via condensation of one acetyl-CoA starter unit with 7
CC malonyl-CoA units and 5 methylations (PubMed:31553484). The C-terminal
CC reductase (R) domain of sthA catalyzes the reductive release of the
CC polyketide chain (PubMed:31553484). Because sthA lacks a designated
CC enoylreductase (ER) domain, the required activity is provided the enoyl
CC reductase sthE (PubMed:31553484). The short-chain
CC dehydrogenase/reductase sthC then catalyzes reduction of
CC dehydroprobetaenone I to probetaenone I (PubMed:31553484). The
CC cytochrome P450 monooxygenase sthF catalyzes successive epoxidation,
CC oxidation (resulting from epoxide opening) and hydroxylation to install
CC a tertiary alcohol in the decaline ring to yield betaenone C from
CC dehydroprobetaenone I and betaenone B from probetaenone I
CC (PubMed:31553484). The FAD-linked oxidoreductase sthB is responsible
CC for the conversion of betaenone C to betaenone A via an intramolecular
CC aldol reaction between C-1 and C-17 to form the bridged tricyclic
CC system in betaenone A (PubMed:31553484). Finally, the cytochrome P450
CC monooxygenase sthD catalyzes the hydroxylation of C-15 to afford the
CC final metabolite stemphyloxin II (PubMed:31553484).
CC {ECO:0000269|PubMed:31553484}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=betaenone A + H(+) + NADPH + O2 = H2O + NADP(+) + stemphyloxin
CC II; Xref=Rhea:RHEA:61904, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:145055, ChEBI:CHEBI:145066;
CC Evidence={ECO:0000269|PubMed:31553484};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61905;
CC Evidence={ECO:0000269|PubMed:31553484};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=betaenone C + H(+) + NADPH + O2 = H2O + NADP(+) + stemphyloxin
CC I; Xref=Rhea:RHEA:62712, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:145053, ChEBI:CHEBI:145070;
CC Evidence={ECO:0000269|PubMed:31553484};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62713;
CC Evidence={ECO:0000269|PubMed:31553484};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:31553484}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; CH445335; EAT85329.1; -; Genomic_DNA.
DR RefSeq; XP_001798190.1; XM_001798138.1.
DR AlphaFoldDB; Q0UK51; -.
DR SMR; Q0UK51; -.
DR GeneID; 5975083; -.
DR KEGG; pno:SNOG_07863; -.
DR InParanoid; Q0UK51; -.
DR OMA; CRFIVIA; -.
DR OrthoDB; 871849at2759; -.
DR Proteomes; UP000001055; Unassembled WGS sequence.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW Oxidoreductase; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..475
FT /note="Cytochrome P450 monooxygenase sthD"
FT /id="PRO_0000448650"
FT TRANSMEM 276..296
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 418
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P04798"
FT CARBOHYD 336
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 475 AA; 53121 MW; 1F79D4EFF4FF1C15 CRC64;
MAAYFLLGLY GSTLVYRLIF HPLNRFPGPL AARISDLWLC TQLGGHDMHH LSERLSKRYG
EFVRIGSSTL MLTHPKAVAA IYGPGSPCRK GTFYDLEQPN RGIATRDESL HAGRRRVWSR
GFGDKALRTY EPRVAAYVHM LLGRLADARG KPVDMARLAE AFAFDTMGDL GLGADFGMLR
QARTHEAVEQ LVQGMTIMGR RLPMWLMRLL IDVAQALVPT AATTGFLGFC HHHLDRFMAD
PRRSERPSLM APLLSHYEKQ NIADRDLSIL RNDCRFIIIA GSDTVAATLT FAFFYLAKHP
GHVTRLREEL FPLRAADGTF SHQRIFDAPH LNAVINETLR LHPPASTIPR VTPPQGLVVA
DTFIPGDMTV FSSQYALGRS EAIYSKASDF IPERWCSRPD LIKDGSAYAP FSIGHHSCLG
RPLALMEMRL VLAETLSRFD IAFAPGFDAN HFLQHVHDCM SWHIGKLGLT FTAIE
