ACRD_ASPA1
ID ACRD_ASPA1 Reviewed; 500 AA.
AC A0A1L9WQP6;
DT 12-AUG-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 acrD {ECO:0000303|PubMed:32234543};
DE EC=1.-.-.- {ECO:0000269|PubMed:32234543};
DE AltName: Full=Acurin A biosynthesis cluster protein D {ECO:0000303|PubMed:32234543};
GN Name=acrD {ECO:0000303|PubMed:32234543}; ORFNames=ASPACDRAFT_45003;
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, PATHWAY, AND INDUCTION.
RX PubMed=32234543; DOI=10.1016/j.fgb.2020.103378;
RA Wolff P.B., Nielsen M.L., Slot J.C., Andersen L.N., Petersen L.M.,
RA Isbrandt T., Holm D.K., Mortensen U.H., Noedvig C.S., Larsen T.O.,
RA Hoof J.B.;
RT "Acurin A, a novel hybrid compound, biosynthesized by individually
RT translated PKS- and NRPS-encoding genes in Aspergillus aculeatus.";
RL Fungal Genet. Biol. 139:103378-103378(2020).
CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the cluster that
CC mediates the biosynthesis of acurin A, a highly reduced polyketide
CC coupled to a serine via a peptide bond (PubMed:32234543). The
CC activities of the highly reducing polyketide synthase acrA and the
CC nonribosomal peptide synthetase acrB are collectively responsible for
CC the synthesis of the acurin A core structure with a heptaketide
CC backbone produced by acrA covalently fused to a L-serine by acrB
CC (PubMed:32234543). After the formation of the PK-NRP hybrid product, it
CC is detached from acrB by reductive release to set up the formation of
CC the lactam ring by aldol condensation (Probable). The hydrolyase acrC
CC then catalyzes water loss to generate a double bond in the ring
CC (Probable). This double bond is probably reduced, which is followed by
CC three oxidations at C-22 to generate the carboxylic acid moiety,
CC involving probably the FAD-binding monooxygenase acrE and the
CC cytochrome P450 monooxygenases acrD and acrF (Probable). Finally, a
CC last methylation step performed by the O-methyltransferase acrG leads
CC to the production of acurin A (Probable). {ECO:0000269|PubMed:32234543,
CC ECO:0000305|PubMed:32234543}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:32234543}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- INDUCTION: Expression is positively regulated by the acurin A cluster-
CC specific transcription regulator acrR. {ECO:0000269|PubMed:32234543}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of acurin A.
CC {ECO:0000269|PubMed:32234543}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; KV878980; OJJ98490.1; -; Genomic_DNA.
DR RefSeq; XP_020054830.1; XM_020201528.1.
DR AlphaFoldDB; A0A1L9WQP6; -.
DR SMR; A0A1L9WQP6; -.
DR STRING; 690307.A0A1L9WQP6; -.
DR EnsemblFungi; OJJ98490; OJJ98490; ASPACDRAFT_45003.
DR GeneID; 30975342; -.
DR VEuPathDB; FungiDB:ASPACDRAFT_45003; -.
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 2: Evidence at transcript level;
KW Glycoprotein; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW Oxidoreductase; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..500
FT /note="Cytochrome P450 monooxygenase acrD"
FT /id="PRO_0000450417"
FT TRANSMEM 13..32
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"
FT CARBOHYD 210
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 414
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 500 AA; 56913 MW; 1B62210004E43DF5 CRC64;
MAEIHDITGL LKPYLSGTNL VWTLLLVGYI IPKLFQYLQR LFSPVSRIPG SWLHKLTSLP
LKIAIAKGES HIFTVDLHKK YGPIVTLSPT MISISDAREI KRIVHTEDWA KSEAVYGNFR
QDPQRPTLLA FTDKKAYSQR KRLVSSMFGL RYIRSMQPLM RNCISVLMDE LDKQCANGAT
AVDMQHMIQS LAADIIGVTT FGQTFDLVKN GSHPLPDRLK QALKLSGILQ FMPWLTKIPF
IPNRDPYVSW FTNEIVAKRR AQIASRQGPP REDLLQKMIE AADESPTSPF RVSDIQDESV
VLLIAGSETT ANAELFTLIH LLRHPSKLAT LYEEIDRWYP RNDPRPTDCD YSMSGMVYLQ
ACIDETMRLV PGQATGSPRE SRKDETLLGY DIPKGTTVFP TTQEVHLDET LWPNATEFLP
ERWLDVYAKG EANSLPYYPF SAGSRVCIGK HFAAQEMHLS LVSLLRRFQF EYVSGQDEST
VFRIAQQMRG HRYLMTVGRR
