ACUC_ASPA1
ID ACUC_ASPA1 Reviewed; 531 AA.
AC A0A1L9WN31;
DT 12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2017, sequence version 1.
DT 03-AUG-2022, entry version 19.
DE RecName: Full=Cytochrome P450 monooxygenase acuC {ECO:0000303|PubMed:26374386};
DE EC=1.-.-.- {ECO:0000305|PubMed:26374386};
DE AltName: Full=Aculin biosynthesis cluster protein C {ECO:0000303|PubMed:26374386};
DE AltName: Full=m-cresol hydrolase acuC {ECO:0000303|PubMed:26374386};
GN Name=acuC {ECO:0000303|PubMed:26374386}; ORFNames=ASPACDRAFT_45673;
OS Aspergillus aculeatus (strain ATCC 16872 / CBS 172.66 / WB 5094).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=690307;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 16872 / CBS 172.66 / WB 5094;
RX PubMed=28196534; DOI=10.1186/s13059-017-1151-0;
RA de Vries R.P., Riley R., Wiebenga A., Aguilar-Osorio G., Amillis S.,
RA Uchima C.A., Anderluh G., Asadollahi M., Askin M., Barry K., Battaglia E.,
RA Bayram O., Benocci T., Braus-Stromeyer S.A., Caldana C., Canovas D.,
RA Cerqueira G.C., Chen F., Chen W., Choi C., Clum A., Dos Santos R.A.,
RA Damasio A.R., Diallinas G., Emri T., Fekete E., Flipphi M., Freyberg S.,
RA Gallo A., Gournas C., Habgood R., Hainaut M., Harispe M.L., Henrissat B.,
RA Hilden K.S., Hope R., Hossain A., Karabika E., Karaffa L., Karanyi Z.,
RA Krasevec N., Kuo A., Kusch H., LaButti K., Lagendijk E.L., Lapidus A.,
RA Levasseur A., Lindquist E., Lipzen A., Logrieco A.F., MacCabe A.,
RA Maekelae M.R., Malavazi I., Melin P., Meyer V., Mielnichuk N., Miskei M.,
RA Molnar A.P., Mule G., Ngan C.Y., Orejas M., Orosz E., Ouedraogo J.P.,
RA Overkamp K.M., Park H.-S., Perrone G., Piumi F., Punt P.J., Ram A.F.,
RA Ramon A., Rauscher S., Record E., Riano-Pachon D.M., Robert V., Roehrig J.,
RA Ruller R., Salamov A., Salih N.S., Samson R.A., Sandor E., Sanguinetti M.,
RA Schuetze T., Sepcic K., Shelest E., Sherlock G., Sophianopoulou V.,
RA Squina F.M., Sun H., Susca A., Todd R.B., Tsang A., Unkles S.E.,
RA van de Wiele N., van Rossen-Uffink D., Oliveira J.V., Vesth T.C.,
RA Visser J., Yu J.-H., Zhou M., Andersen M.R., Archer D.B., Baker S.E.,
RA Benoit I., Brakhage A.A., Braus G.H., Fischer R., Frisvad J.C.,
RA Goldman G.H., Houbraken J., Oakley B., Pocsi I., Scazzocchio C.,
RA Seiboth B., vanKuyk P.A., Wortman J., Dyer P.S., Grigoriev I.V.;
RT "Comparative genomics reveals high biological diversity and specific
RT adaptations in the industrially and medically important fungal genus
RT Aspergillus.";
RL Genome Biol. 18:RESEARCH28.1-RESEARCH28.45(2017).
RN [2]
RP FUNCTION, AND PATHWAY.
RX PubMed=26374386; DOI=10.1002/cbic.201500210;
RA Petersen L.M., Holm D.K., Gotfredsen C.H., Mortensen U.H., Larsen T.O.;
RT "Investigation of a 6-MSA Synthase Gene Cluster in Aspergillus aculeatus
RT Reveals 6-MSA-derived Aculinic Acid, Aculins A-B and Epi-Aculin A.";
RL ChemBioChem 16:2200-2204(2015).
CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of aculins (PubMed:26374386). The pathway
CC begins with the synthesis of 6-methylsalicylic acid by the polyketide
CC synthase (PKS) acuA via condensation of acetate and malonate units
CC (PubMed:26374386). The 6-methylsalicylic acid decarboxylase acuB then
CC catalyzes the decarboxylation of 6-methylsalicylic acid to yield m-
CC cresol (also known as 3-methylphenol) (Probable). These first reactions
CC occur in the cytosol (By similarity). The intermediate m-cresol is then
CC transported into the endoplasmic reticulum where the cytochrome P450
CC monooxygenase acuC converts it to m-hydroxybenzyl alcohol, which is
CC further converted to gentisyl alcohol by the cytochrome P450
CC monooxygenase acuD (Probable). Gentisyl alcohol is further oxidized by
CC the oxidoreductase acuE that probably catalyzes hydroxylation of the
CC aromatic ring (Probable). The aromatic system might then be opened by
CC oxidation through a Baeyer-Villiger type of oxidation, which could be
CC catalyzed by acuF, with the carboxylic acid at C-1 subsequently reduced
CC to an aldehyde by acuG (Probable). Subsequently, a hemiacetal is
CC formed, before the dehydrogenase acuH would reduce the double bond
CC between C-4 and C-6 (Probable). Finally, keto-enol tautomerism results
CC in formation of aculinic acid, which exists as two diastereomers (both
CC R/S configurations at C-1) by non-enzymatic hemiacetal formation
CC (Probable). The carboxypeptidase acuI could be involved in the linking
CC of aculinic acid to an aculene A moiety produced by the aculene
CC biosynthesis cluster and which leads to the production of aculin A
CC (Probable). AcuI may also be involved in the attachment of proline to
CC aculinic acid to form epi-aculins A and B (Probable).
CC {ECO:0000250|UniProtKB:A0A075TRC0, ECO:0000269|PubMed:26374386,
CC ECO:0000305|PubMed:26374386}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-methylphenol + O2 + reduced [NADPH--hemoprotein reductase] =
CC 3-hydroxybenzyl alcohol + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:62208, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:17069, ChEBI:CHEBI:17231, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; Evidence={ECO:0000305|PubMed:26374386};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62209;
CC Evidence={ECO:0000305|PubMed:26374386};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000305|PubMed:26374386}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:A0A075TRL5}; Single-pass membrane protein
CC {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; KV878982; OJJ97582.1; -; Genomic_DNA.
DR RefSeq; XP_020053922.1; XM_020201650.1.
DR AlphaFoldDB; A0A1L9WN31; -.
DR SMR; A0A1L9WN31; -.
DR STRING; 690307.A0A1L9WN31; -.
DR EnsemblFungi; OJJ97582; OJJ97582; ASPACDRAFT_45673.
DR GeneID; 30975464; -.
DR VEuPathDB; FungiDB:ASPACDRAFT_45673; -.
DR OrthoDB; 702827at2759; -.
DR Proteomes; UP000184546; Unassembled WGS sequence.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
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; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR SUPFAM; SSF48264; SSF48264; 1.
PE 3: Inferred from homology;
KW Endoplasmic reticulum; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW Oxidoreductase; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..531
FT /note="Cytochrome P450 monooxygenase acuC"
FT /id="PRO_0000450415"
FT TRANSMEM 3..23
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 447
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"
SQ SEQUENCE 531 AA; 60559 MW; 8B45EF19F01AF12B CRC64;
MQPIVWLLGG AIALLVVVIR AAWTYGHRNQ DMPSGPPTLP FIGNAHLIPK SYTHIQFTAW
ARQYGGLYML KVGNSNMAVV TDRRIVKEVL DSKSSLYSHR PHSFVSHELI TQGDHLLVMH
YGPKWRTFRR LVHQHLMESM VDSQHLPIVN AEAIQLVRDY MLDPEHHMAH PKRFSNSITN
SIVFGIRTAD RHGSNMNRLY TLMEQWSEIM ETGATPPVDI FPWLKRLPEA LFGHYVTRAR
AIGAQMETLY EDILQRVEKR RSGGVHLDTF MDRVIASQDR NQLPRHQLAF IGGVLMEGGS
DTSSSLTLAI VQALTLHPEV QRKAHAEIDA VVGHARSPVW DDLARLPYIN MIIKEGHRWR
PILPLCFPHA LGQDDWVDGK FLPKGTMVVV NTWGMHMDPD HRLNQKYDPA KFVPERFAEH
PALAPEYVPG AWENRDHYGY GVSRRICPGI HLAERNMFLA IAKLLWAFEF QPGPEGEPCD
SDPVTGYQHG FLYCAKPYST RPVLRSESIR ETVEREFALA QREVFSTFTE G
