ANEF_ASPA1
ID ANEF_ASPA1 Reviewed; 495 AA.
AC A0A1L9WVI3;
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 aneF {ECO:0000303|PubMed:31618514};
DE EC=1.-.-.- {ECO:0000269|PubMed:31618514};
DE AltName: Full=Aculenes biosynthesis cluster protein F {ECO:0000303|PubMed:31618514};
GN Name=aneF {ECO:0000303|PubMed:31618514}; ORFNames=ASPACDRAFT_78841;
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=dauca-4,7-diene + 3 O2 + 3 reduced [NADPH--hemoprotein
CC reductase] = asperaculane D + 4 H(+) + 4 H2O + 3 oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:65076, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:155906, ChEBI:CHEBI:155907;
CC Evidence={ECO:0000269|PubMed:31618514};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65077;
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 dauca-4,7-diene. {ECO:0000269|PubMed:31618514}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; KV878977; OJJ99917.1; -; Genomic_DNA.
DR RefSeq; XP_020056257.1; XM_020205278.1.
DR AlphaFoldDB; A0A1L9WVI3; -.
DR SMR; A0A1L9WVI3; -.
DR EnsemblFungi; OJJ99917; OJJ99917; ASPACDRAFT_78841.
DR GeneID; 30979092; -.
DR VEuPathDB; FungiDB:ASPACDRAFT_78841; -.
DR OrthoDB; 467733at2759; -.
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..495
FT /note="Cytochrome P450 monooxygenase aneF"
FT /id="PRO_0000449094"
FT TRANSMEM 1..21
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 437
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 47
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 495 AA; 56431 MW; 4897BB20FF7166F4 CRC64;
MIAGLVLVVL LTKYLQRVFL HPLSKFPGPS IAAVSHLWEF WHDWVKNGTF LEGVADLHRS
YKSPVVRIAP NHLHVNDVEV YHQVFKVNTN FYKAPYFYEA FGFATSIATI TNPHRHKPLR
TTVAPMFTGT AVDGMSDEMY DMVRKATDLL AARSTGTGNK FNVMQFLRCI TTDVSCNLIF
GETLDLVSNG YHSDRFLGNL DTFVENVWIM VHAPWIAQFA LMLPNSLTDK IVPGYAYFRE
QCISWIDKVR ARRAKGITLM RNGRPTLFDV LMDDNPDKNY KVPSKSELID QAFLFAIAGT
DTTSMATTFA VFHILNNPAV RERLCEELRG ASAIIRDQYN YREVRKLPYL SAVIKEALRM
SSPFPGRLPR VVPPEGMKLD NKFVPGGTII SISSRCIMDD PKIYPEPEKF LPERWMGENA
KSMDRNMIAF GKGSRSCLGT NLAYLKMYTM LSTMFCRWDL RLVSPTDHKL RYLDHALIEM
KSQVVVEILA DHWTT
