ANEG_ASPA1
ID ANEG_ASPA1 Reviewed; 530 AA.
AC A0A1L9WUV2;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2017, sequence version 1.
DT 03-AUG-2022, entry version 18.
DE RecName: Full=Cytochrome P450 monooxygenase aneG {ECO:0000303|PubMed:31618514};
DE EC=1.-.-.- {ECO:0000269|PubMed:31618514};
DE AltName: Full=Aculenes biosynthesis cluster protein G {ECO:0000303|PubMed:31618514};
GN Name=aneG {ECO:0000303|PubMed:31618514}; ORFNames=ASPACDRAFT_119792;
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, DISRUPTION PHENOTYPE, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=31618514; DOI=10.1002/anie.201910200;
RA Lee C.F., Chen L.X., Chiang C.Y., Lai C.Y., Lin H.C.;
RT "The biosynthesis of norsesquiterpene aculenes requires three cytochrome
RT P450 enzymes to catalyze a stepwise demethylation process.";
RL Angew. Chem. Int. Ed. 58:18414-18418(2019).
CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of aculenes, a unique type of
CC norsesquiterpenes that contain a nordaucane skeleton linked to an L-
CC proline moiety and are of mixed biosynthetic origin (PubMed:31618514).
CC The pathway begins with the synthesis of dauca-4,7-diene by the terpene
CC cyclase aneC using farnesyl pyrophosphate (FPP) as substrate
CC (PubMed:31618514). The cytochrome P450 monooxygenase aneF then performs
CC the initial oxidation at C-12 of dauca-4,7-diene to yield asperaculane
CC D (PubMed:31618514). Asperaculane D is substrate of the cytochrome P450
CC monooxygenase aneD for C-10 hydroxylation to yield asperaculane E
CC (PubMed:31618514). The cytochrome P450 monooxygenase aneG then converts
CC asperaculane E into aculene D via C-2 oxidation (PubMed:31618514). The
CC monomodular nonribosomal peptide synthtase aneB adenylates L-proline
CC and the thiohydrolase aneE transfers this activated L-proline
CC derivative to aculenes D and C to produce respectively aculenes B and A
CC (PubMed:31618514). The dioxygenase aneA converts aculene D into aculene
CC C, and aculene B into aculene A by introducing the 5,6-alkene moiety
CC (PubMed:31618514). Asperculanes A, B, C and F, as well as 14-prolyl
CC asperculane C, might be shunt products of the pathway
CC (PubMed:31618514). {ECO:0000269|PubMed:31618514}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=asperaculane E + O2 + reduced [NADPH--hemoprotein reductase] =
CC asperaculane G + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:65088, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:155909,
CC ChEBI:CHEBI:155911; Evidence={ECO:0000269|PubMed:31618514};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65089;
CC Evidence={ECO:0000269|PubMed:31618514};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=asperaculane G + O2 + reduced [NADPH--hemoprotein reductase] =
CC aculene D + CO2 + 2 H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:65092, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:155910,
CC ChEBI:CHEBI:155911; Evidence={ECO:0000269|PubMed:31618514};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65093;
CC Evidence={ECO:0000269|PubMed:31618514};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=asperaculane E + 2 O2 + 2 reduced [NADPH--hemoprotein
CC reductase] = aculene D + CO2 + H(+) + 3 H2O + 2 oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:65084, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:155909, ChEBI:CHEBI:155910;
CC Evidence={ECO:0000269|PubMed:31618514};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65085;
CC Evidence={ECO:0000269|PubMed:31618514};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:31618514}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the formation of aculene A and
CC accumulates a major product,asperculane A, along with two minor
CC products, asperculane C and 14-prolyl asperculane C.
CC {ECO:0000269|PubMed:31618514}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; KV878977; OJJ99918.1; -; Genomic_DNA.
DR RefSeq; XP_020056258.1; XM_020196278.1.
DR AlphaFoldDB; A0A1L9WUV2; -.
DR SMR; A0A1L9WUV2; -.
DR EnsemblFungi; OJJ99918; OJJ99918; ASPACDRAFT_119792.
DR GeneID; 30970092; -.
DR VEuPathDB; FungiDB:ASPACDRAFT_119792; -.
DR OrthoDB; 481145at2759; -.
DR Proteomes; UP000184546; 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; Transmembrane; Transmembrane helix.
FT CHAIN 1..530
FT /note="Cytochrome P450 monooxygenase aneG"
FT /id="PRO_0000449095"
FT TRANSMEM 43..63
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 474
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 2
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 92
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 530 AA; 59968 MW; 43B061465172BE79 CRC64;
MNATAQALVL PFITQVTRAV SLSENVKVLG GIPFAEDGTY LEWLSILGFT IGCYYVIYTF
YALCFHPLRK YPGPWHLAVS NIPNRWSTIS GNSSYWLYDL HEKYGPIVRV APNEISYSDP
QAWQDIYGPQ PNQRLGMPKD PKFFSSFEDK KTAASIITSQ PKDYMRMRHI YSYGFSKQVM
LAKEEMIQGI IDRAMEALRQ TKQQPQDIVQ IFRATDFSIV TEIVFGKAYH IFDRPTYQPW
FKSLMGWIRS TAVITATTDY PLGKLAAWLL TPRSVLKQRN VYLKYVNGEI EERIGESNAG
RKDVVQLMFE TTDQPKLAES DIRANLPFMV IAASETTTTL MSGMIAHLLN SPDALSQLTA
EVRGRFRSPS DITIATVNNL PFLNACVNEA LRVYPAAPTQ LPRVVPGEGA TVCNRWVPGG
TKVYVAPYAT FRSAENFYQP DAFLPQRWLP ENGESFDVDK KNAWRPFGLG AHECPGQVIT
NLITRLIMCK LLLSFDLELC ADSQDWLSRQ PVWIVWDKPE LLIKARPAAA
