ANEA_ASPA1
ID ANEA_ASPA1 Reviewed; 298 AA.
AC A0A1L9WUX8;
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=Dioxygenase aneA {ECO:0000303|PubMed:31618514};
DE EC=1.14.11.- {ECO:0000269|PubMed:31618514};
DE AltName: Full=Aculenes biosynthesis cluster protein A {ECO:0000303|PubMed:31618514};
GN Name=aneA {ECO:0000303|PubMed:31618514}; ORFNames=ASPACDRAFT_119783;
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: Dioxygenase; part of the gene cluster that mediates the
CC biosynthesis of aculenes, a unique type of norsesquiterpenes that
CC contain a nordaucane skeleton linked to an L-proline moiety and are of
CC mixed biosynthetic origin (PubMed:31618514). The pathway begins with
CC the synthesis of dauca-4,7-diene by the terpene cyclase aneC using
CC farnesyl pyrophosphate (FPP) as substrate (PubMed:31618514). The
CC cytochrome P450 monooxygenase aneF then performs the initial oxidation
CC at C-12 of dauca-4,7-diene to yield asperaculane D (PubMed:31618514).
CC Asperaculane D is substrate of the cytochrome P450 monooxygenase aneD
CC for C-10 hydroxylation to yield asperaculane E (PubMed:31618514). The
CC cytochrome P450 monooxygenase aneG then converts asperaculane E into
CC aculene D via C-2 oxidation (PubMed:31618514). The monomodular
CC nonribosomal peptide synthase aneB adenylates L-proline and the
CC thiohydrolase aneE transfers this activated L-proline derivative to
CC 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=2-oxoglutarate + aculene D + O2 = aculene C + CO2 + H2O +
CC succinate; Xref=Rhea:RHEA:65112, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:30031, ChEBI:CHEBI:155910, ChEBI:CHEBI:155912;
CC Evidence={ECO:0000269|PubMed:31618514};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65113;
CC Evidence={ECO:0000269|PubMed:31618514};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + aculene B + O2 = aculene A + CO2 + H2O +
CC succinate; Xref=Rhea:RHEA:65116, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:30031, ChEBI:CHEBI:155913, ChEBI:CHEBI:155914;
CC Evidence={ECO:0000269|PubMed:31618514};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65117;
CC Evidence={ECO:0000269|PubMed:31618514};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000250|UniProtKB:Q4WAW9};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:31618514}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q4WAW9}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of aculenes A and C, and
CC accumulates aculenes B and D, as well as a minor component,
CC asperaculane B. {ECO:0000269|PubMed:31618514}.
CC -!- SIMILARITY: Belongs to the PhyH family. {ECO:0000305}.
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DR EMBL; KV878977; OJJ99912.1; -; Genomic_DNA.
DR RefSeq; XP_020056252.1; XM_020196277.1.
DR AlphaFoldDB; A0A1L9WUX8; -.
DR SMR; A0A1L9WUX8; -.
DR EnsemblFungi; OJJ99912; OJJ99912; ASPACDRAFT_119783.
DR GeneID; 30970091; -.
DR VEuPathDB; FungiDB:ASPACDRAFT_119783; -.
DR OrthoDB; 623398at2759; -.
DR Proteomes; UP000184546; Unassembled WGS sequence.
DR GO; GO:0051213; F:dioxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR InterPro; IPR008775; Phytyl_CoA_dOase.
DR Pfam; PF05721; PhyH; 1.
PE 1: Evidence at protein level;
KW Dioxygenase; Iron; Metal-binding; Oxidoreductase; Reference proteome.
FT CHAIN 1..298
FT /note="Dioxygenase aneA"
FT /id="PRO_0000449090"
FT BINDING 134
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:O14832"
FT BINDING 136
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:O14832"
FT BINDING 213
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:O14832"
SQ SEQUENCE 298 AA; 33049 MW; 0C4B8D54D1611ACD CRC64;
MTRSSPKSIL RRVAAHEGAP KILQVLKEDG AVIIRGFLNQ NLFQKLNKEM EDELAKRPLI
CEHNGEWVSG LAGSQTRRLN QLPAFSPTFR QEILNHPLFH EICEPLFGTH GCDYWMNTAT
VVQIGPGNAA QSLHRDQELY PVFNPIGKDA PEALVNFFCA LSTFTDENGA TRVIPGSHQW
DDFTTDVTRC VPQTIPAEME AGDCLLFSGK TVHGGGANRS KDNVRRGMAL GVQATYLTAE
ENYQHIPREI VESMTPLAQK MIHWRSSYCP GGAGLWQING TELANEIGLK ANQPKKTI
