ANED_ASPA1
ID ANED_ASPA1 Reviewed; 514 AA.
AC A0A1L9WUS5;
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 aneD {ECO:0000303|PubMed:31618514};
DE EC=1.-.-.- {ECO:0000269|PubMed:31618514};
DE AltName: Full=Aculenes biosynthesis cluster protein D {ECO:0000303|PubMed:31618514};
GN Name=aneD {ECO:0000303|PubMed:31618514}; ORFNames=ASPACDRAFT_60732;
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 D + O2 + reduced [NADPH--hemoprotein reductase] =
CC asperaculane E + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:65080, 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:155907,
CC ChEBI:CHEBI:155909; Evidence={ECO:0000269|PubMed:31618514};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65081;
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 asperculane C as a major product and 14-prolyl asperculane
CC C as a minor product. {ECO:0000269|PubMed:31618514}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; KV878977; OJJ99915.1; -; Genomic_DNA.
DR RefSeq; XP_020056255.1; XM_020203589.1.
DR AlphaFoldDB; A0A1L9WUS5; -.
DR SMR; A0A1L9WUS5; -.
DR EnsemblFungi; OJJ99915; OJJ99915; ASPACDRAFT_60732.
DR GeneID; 30977403; -.
DR VEuPathDB; FungiDB:ASPACDRAFT_60732; -.
DR OrthoDB; 702827at2759; -.
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..514
FT /note="Cytochrome P450 monooxygenase aneD"
FT /id="PRO_0000449093"
FT TRANSMEM 6..26
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 424
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 113
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 261
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 347
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 514 AA; 57926 MW; 325437D0C562A67F CRC64;
MMSAAICTLL AVIATTSLGL LFLSIIRRGK LPPGPPPKPI VGNLHQFPKV NRAQVFDQWH
RTYGPIVGLR LGLKKLILVG SYQVARELLD RRGAIYSSRP RVVMAGEIAN RGNHTALMPY
GPKWKLHNRV HSALMNPTMV KRYQYLQDIE SRQLVHDLLQ GSTSDFGARI HRYSSSLLFA
LAYGRRLPTS DAFEIQENAH IAHQFINNLA AGRWLVDAFP VLNYLPTWLA PWKKIGEQLY
QRKFGLLQRH TALALEKPVW NWTKHFHGPK KPAEASWEEL LNIIGVLYEA GADTTTSALE
AFVMAAVLHP DAVRRVQAEI DALVGGAARM PSFEDVQQLP FVDAFVNETM RWRPIAPEGV
PHSLMKEDEY EGFTIPKNSI VIANQWHMAM DPATFTDPQA FRPERWLEDP KLPISAFGFG
RRACPGRHIA LNSMKIVMCR LLWAYDFDHA YENGRKVTID PDNFVREGVL SKPAPFKAAL
RVRSPAHEKT IQSALRESEQ DEDKILAHIA AGLA
