ASTD_ASPOR
ID ASTD_ASPOR Reviewed; 512 AA.
AC Q2UEK5;
DT 17-JUN-2020, integrated into UniProtKB/Swiss-Prot.
DT 24-JAN-2006, sequence version 1.
DT 03-AUG-2022, entry version 83.
DE RecName: Full=Cytochrome P450 monooxygenase astD {ECO:0000303|PubMed:27628599};
DE EC=1.-.-.- {ECO:0000305|PubMed:27628599};
DE AltName: Full=Astellolide biosynthesis cluster protein D {ECO:0000303|PubMed:27628599};
GN Name=astD {ECO:0000303|PubMed:27628599}; ORFNames=AO090026000581;
OS Aspergillus oryzae (strain ATCC 42149 / RIB 40) (Yellow koji mold).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=510516;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 42149 / RIB 40;
RX PubMed=16372010; DOI=10.1038/nature04300;
RA Machida M., Asai K., Sano M., Tanaka T., Kumagai T., Terai G., Kusumoto K.,
RA Arima T., Akita O., Kashiwagi Y., Abe K., Gomi K., Horiuchi H.,
RA Kitamoto K., Kobayashi T., Takeuchi M., Denning D.W., Galagan J.E.,
RA Nierman W.C., Yu J., Archer D.B., Bennett J.W., Bhatnagar D.,
RA Cleveland T.E., Fedorova N.D., Gotoh O., Horikawa H., Hosoyama A.,
RA Ichinomiya M., Igarashi R., Iwashita K., Juvvadi P.R., Kato M., Kato Y.,
RA Kin T., Kokubun A., Maeda H., Maeyama N., Maruyama J., Nagasaki H.,
RA Nakajima T., Oda K., Okada K., Paulsen I., Sakamoto K., Sawano T.,
RA Takahashi M., Takase K., Terabayashi Y., Wortman J.R., Yamada O.,
RA Yamagata Y., Anazawa H., Hata Y., Koide Y., Komori T., Koyama Y.,
RA Minetoki T., Suharnan S., Tanaka A., Isono K., Kuhara S., Ogasawara N.,
RA Kikuchi H.;
RT "Genome sequencing and analysis of Aspergillus oryzae.";
RL Nature 438:1157-1161(2005).
RN [2]
RP INDUCTION, FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=27628599; DOI=10.1038/srep32865;
RA Shinohara Y., Takahashi S., Osada H., Koyama Y.;
RT "Identification of a novel sesquiterpene biosynthetic machinery involved in
RT astellolide biosynthesis.";
RL Sci. Rep. 6:32865-32865(2016).
CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of astellolides, drimane-type sesquiterpene
CC esters that show antimicrobial, anti-inflammatory, and anti-tumor
CC activities (PubMed:27628599). The first step in astellolide
CC biosynthesis is performed by the sesquiterpene cyclase astC that
CC catalyzes the formation of drimanyl pyrophosphate from farnesyl
CC pyrophosphate (PubMed:27628599). Drimanyl pyrophosphate is then
CC dephosphorylated by the sesquiterpene phosphatase astI to produce
CC drimanyl monophosphate which is further dephosphorylated to drim-8-ene-
CC 11-ol by atsK (PubMed:27628599). Drim-8-ene-11-ol is converted to
CC confertifolin, probably by the cytochrome P450 monooxygenase astD
CC and/or the dehydrogenase astE (PubMed:27628599). The cytochrome P450
CC monooxygenases astB, astF and astJ then hydroxylate confertifolin at
CC C6, C14, or C15 to form trihydroxy confertifolin (PubMed:27628599). The
CC nonribosomal peptide synthetase astA catalyzes ester bond formation
CC between trihydroxy contifolin and benzoic acid (BA) or 4-hydroxy
CC benzoic acid (4HBA), leading to the formation of dideacetyl
CC astellolides A and B, respectively (PubMed:27628599). Finally, the O-
CC acetyltransferase astG converts dideacetyl astellolides A and B into
CC deacetyl astellolides A and B (PubMed:27628599).
CC {ECO:0000269|PubMed:27628599}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:27628599}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- INDUCTION: Expression is regulated by the secondary metabolite
CC regulator cclA. {ECO:0000269|PubMed:27628599}.
CC -!- DISRUPTION PHENOTYPE: Leads to the loss of intermediates such as
CC confertifolin. {ECO:0000269|PubMed:27628599}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; AP007159; BAE60010.1; -; Genomic_DNA.
DR RefSeq; XP_001822012.2; XM_001821960.2.
DR AlphaFoldDB; Q2UEK5; -.
DR SMR; Q2UEK5; -.
DR EnsemblFungi; BAE60010; BAE60010; AO090026000581.
DR GeneID; 5994040; -.
DR KEGG; aor:AO090026000581; -.
DR VEuPathDB; FungiDB:AO090026000581; -.
DR HOGENOM; CLU_001570_14_11_1; -.
DR OMA; YETINEC; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000006564; Chromosome 3.
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 GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
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..512
FT /note="Cytochrome P450 monooxygenase astD"
FT /id="PRO_0000450115"
FT TRANSMEM 19..39
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 449
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 191
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 413
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 512 AA; 57813 MW; 84B341CBE3D14E68 CRC64;
MEALPTYLES FWHSGGGTMG ISILVMLSTF LALGTIFVYR IWLHPLSGFP GPKCCSVSSI
PVAWAQLRGR NHEFVSSLHR KYGSVVRISP SELSFISGAA WNDIYSRSKG RPALERDRTF
FNDMLVDPET ITMANEATHS RIRRAMAPAF SPRALLEQEP IIQANIKLLM DKLEARAGSG
GAPTDLRAWF NYTTFDLIGD LAFGESFGCL ATSTCHEWVQ FVLDHFYTST LLHVVHRFHP
FNRVLAALLP KSLIEKRKAH DSMTLTKVHR RLEVQGRRND FTQHLLDAAE AGTLSSREVE
KQASVLILAG SETTSVALTF AIYLVLTNKP VLDQLNDELH STFKEEQEIN LLSVNQLKYL
HAVIQEALRF CPPISNGFPR QTPPQGATVD GMFIPGKTVV NINHWAAYRS PRNFTLPEQF
LPERWLGDPR FDEDAKDVFQ PFSVGPRNCI GKKFAYDSMK LILAKFLWRF KPTLLDKSRS
WLAHQPTFVS FHQPPLLVDL EIKGSDAFPV RE
