ID   APDE_EMENI              Reviewed;         519 AA.
AC   Q5ATG9; C8VEB2;
DT   30-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT   26-APR-2005, sequence version 1.
DT   03-AUG-2022, entry version 120.
DE   RecName: Full=Cytochrome P450 monooxygenase apdE {ECO:0000303|PubMed:17369821};
DE            EC=1.-.-.- {ECO:0000269|Ref.5};
DE   AltName: Full=Aspyridones biosynthesis protein E {ECO:0000303|PubMed:17369821};
GN   Name=apdE {ECO:0000303|PubMed:17369821}; ORFNames=AN8411;
OS   Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 /
OS   M139) (Aspergillus nidulans).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC   Aspergillus subgen. Nidulantes.
OX   NCBI_TaxID=227321;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX   PubMed=16372000; DOI=10.1038/nature04341;
RA   Galagan J.E., Calvo S.E., Cuomo C., Ma L.-J., Wortman J.R., Batzoglou S.,
RA   Lee S.-I., Bastuerkmen M., Spevak C.C., Clutterbuck J., Kapitonov V.,
RA   Jurka J., Scazzocchio C., Farman M.L., Butler J., Purcell S., Harris S.,
RA   Braus G.H., Draht O., Busch S., D'Enfert C., Bouchier C., Goldman G.H.,
RA   Bell-Pedersen D., Griffiths-Jones S., Doonan J.H., Yu J., Vienken K.,
RA   Pain A., Freitag M., Selker E.U., Archer D.B., Penalva M.A., Oakley B.R.,
RA   Momany M., Tanaka T., Kumagai T., Asai K., Machida M., Nierman W.C.,
RA   Denning D.W., Caddick M.X., Hynes M., Paoletti M., Fischer R., Miller B.L.,
RA   Dyer P.S., Sachs M.S., Osmani S.A., Birren B.W.;
RT   "Sequencing of Aspergillus nidulans and comparative analysis with A.
RT   fumigatus and A. oryzae.";
RL   Nature 438:1105-1115(2005).
RN   [2]
RP   GENOME REANNOTATION.
RC   STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX   PubMed=19146970; DOI=10.1016/j.fgb.2008.12.003;
RA   Wortman J.R., Gilsenan J.M., Joardar V., Deegan J., Clutterbuck J.,
RA   Andersen M.R., Archer D., Bencina M., Braus G., Coutinho P., von Dohren H.,
RA   Doonan J., Driessen A.J., Durek P., Espeso E., Fekete E., Flipphi M.,
RA   Estrada C.G., Geysens S., Goldman G., de Groot P.W., Hansen K.,
RA   Harris S.D., Heinekamp T., Helmstaedt K., Henrissat B., Hofmann G.,
RA   Homan T., Horio T., Horiuchi H., James S., Jones M., Karaffa L.,
RA   Karanyi Z., Kato M., Keller N., Kelly D.E., Kiel J.A., Kim J.M.,
RA   van der Klei I.J., Klis F.M., Kovalchuk A., Krasevec N., Kubicek C.P.,
RA   Liu B., Maccabe A., Meyer V., Mirabito P., Miskei M., Mos M., Mullins J.,
RA   Nelson D.R., Nielsen J., Oakley B.R., Osmani S.A., Pakula T., Paszewski A.,
RA   Paulsen I., Pilsyk S., Pocsi I., Punt P.J., Ram A.F., Ren Q., Robellet X.,
RA   Robson G., Seiboth B., van Solingen P., Specht T., Sun J.,
RA   Taheri-Talesh N., Takeshita N., Ussery D., vanKuyk P.A., Visser H.,
RA   van de Vondervoort P.J., de Vries R.P., Walton J., Xiang X., Xiong Y.,
RA   Zeng A.P., Brandt B.W., Cornell M.J., van den Hondel C.A., Visser J.,
RA   Oliver S.G., Turner G.;
RT   "The 2008 update of the Aspergillus nidulans genome annotation: a community
RT   effort.";
RL   Fungal Genet. Biol. 46:S2-13(2009).
RN   [3]
RP   FUNCTION, INDUCTION, AND PATHWAY.
RX   PubMed=17369821; DOI=10.1038/nchembio869;
RA   Bergmann S., Schuemann J., Scherlach K., Lange C., Brakhage A.A.,
RA   Hertweck C.;
RT   "Genomics-driven discovery of PKS-NRPS hybrid metabolites from Aspergillus
RT   nidulans.";
RL   Nat. Chem. Biol. 3:213-217(2007).
RN   [4]
RP   FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX   PubMed=20828130; DOI=10.1021/ja107084d;
RA   Xu W., Cai X., Jung M.E., Tang Y.;
RT   "Analysis of intact and dissected fungal polyketide synthase-nonribosomal
RT   peptide synthetase in vitro and in Saccharomyces cerevisiae.";
RL   J. Am. Chem. Soc. 132:13604-13607(2010).
RN   [5]
RP   FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX   DOI=10.1039/c3sc51785c;
RA   Wasil Z., Pahirulzaman K.A.K., Butts C., Simpson T.J., Lazarus C.M.,
RA   Cox R.J.;
RT   "One pathway, many compounds: Heterologous expression of a fungal
RT   biosynthetic pathway reveals its intrinsic potential for diversity.";
RL   Chem. Sci. 4:3845-3856(2013).
RN   [6]
RP   FUNCTION.
RX   PubMed=25494235; DOI=10.1021/ol503179v;
RA   Zou Y., Xu W., Tsunematsu Y., Tang M., Watanabe K., Tang Y.;
RT   "Methylation-dependent acyl transfer between polyketide synthase and
RT   nonribosomal peptide synthetase modules in fungal natural product
RT   biosynthesis.";
RL   Org. Lett. 16:6390-6393(2014).
CC   -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC       mediates the biosynthesis of aspyridones (PubMed:17369821, Ref.5). The
CC       polyketide-amino acid backbone preaspyridone A is first assembled by
CC       the PKS-NRPS hybrid apdA (PubMed:17369821, PubMed:20828130). The
CC       assembly of preaspyridone A is initiated by loading of malonyl-CoA onto
CC       apdA, followed by decarboxylation to yield the acetyl starter unit
CC       (PubMed:20828130). The growing polyketide chain then elongates into a
CC       tetraketide (PubMed:20828130). The adpA PKS module catalyzes three
CC       Claisen condensations, as well as beta-keto processing and methylation
CC       (PubMed:17369821, PubMed:20828130). Alpha-methylation step during
CC       polyketide synthesis is a prerequisite and a key checkpoint for chain
CC       transfer between PKS and NRPS modules (PubMed:25494235). The downstream
CC       NRPS module contains the condensation (C), adenylation (A), and
CC       thiolation (T) domains and catalyzes the incorporation of tyrosine via
CC       the formation of the L-tyrosinyl-thioester and the amide linkage
CC       between L-tyrosinyl-thioester and the tetraketide (PubMed:20828130).
CC       The bimodular assembly line is terminated with a reductase (R) domain
CC       that facilitates formation and release of the tetramic acid product
CC       (PubMed:20828130). Because apdA lacks a designated enoylreductase (ER)
CC       domain, the required activity is provided the enoyl reductase apdC
CC       (PubMed:17369821, PubMed:20828130, Ref.5). ApdC appears to operate with
CC       different stereoselectivity in different PKS cycle (Ref.5). Combined
CC       with apdC, apdA is proposed to synthesize preaspyridone A via about 20
CC       enzymatic steps (PubMed:20828130). A number of oxidative steps
CC       performed successively by the cytochrome P450 monooxygenases apdE and
CC       apdB are required for the conversion of preaspyridone A to aspyridone A
CC       (PubMed:17369821). The cytochrome P450 monooxygenase apdE is
CC       responsible for the oxidative dephenylation of preaspyridone A (Ref.5).
CC       Finally, the predicted FAD-dependent monooxygenase apdD and the acyl-
CC       CoA dehydrogenase apdG may be involved in the transformation of
CC       aspyridone A into aspyridone B (PubMed:17369821) (Probable).
CC       {ECO:0000269|PubMed:17369821, ECO:0000269|PubMed:20828130,
CC       ECO:0000269|PubMed:25494235, ECO:0000269|Ref.5, ECO:0000305|Ref.5}.
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P04798};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:17369821, ECO:0000269|Ref.5}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC       protein {ECO:0000255}.
CC   -!- INDUCTION: Expression is positively regulated by the aspyridones
CC       cluster specific transcription regulator apdR (PubMed:17369821).
CC       {ECO:0000269|PubMed:17369821}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; BN001305; CBF80485.1; -; Genomic_DNA.
DR   EMBL; AACD01000153; EAA67033.1; -; Genomic_DNA.
DR   RefSeq; XP_681680.1; XM_676588.1.
DR   AlphaFoldDB; Q5ATG9; -.
DR   SMR; Q5ATG9; -.
DR   STRING; 162425.CADANIAP00002885; -.
DR   EnsemblFungi; CBF80485; CBF80485; ANIA_08411.
DR   EnsemblFungi; EAA67033; EAA67033; AN8411.2.
DR   GeneID; 2868840; -.
DR   KEGG; ani:AN8411.2; -.
DR   VEuPathDB; FungiDB:AN8411; -.
DR   eggNOG; KOG0158; Eukaryota.
DR   HOGENOM; CLU_001570_27_0_1; -.
DR   InParanoid; Q5ATG9; -.
DR   OMA; RCPAQMM; -.
DR   OrthoDB; 1247045at2759; -.
DR   Proteomes; UP000000560; Chromosome V.
DR   Proteomes; UP000005890; 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:0016712; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen; IEA:InterPro.
DR   GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR   Gene3D; 1.10.630.10; -; 1.
DR   InterPro; IPR001128; Cyt_P450.
DR   InterPro; IPR017972; Cyt_P450_CS.
DR   InterPro; IPR002974; Cyt_P450_E_CYP52.
DR   InterPro; IPR036396; Cyt_P450_sf.
DR   Pfam; PF00067; p450; 1.
DR   PRINTS; PR01239; EP450IICYP52.
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..519
FT                   /note="Cytochrome P450 monooxygenase apdE"
FT                   /id="PRO_0000438448"
FT   TRANSMEM        27..47
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         466
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        327
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        379
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        508
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ   SEQUENCE   519 AA;  60440 MW;  B367EE6EB6FFA287 CRC64;
     MSLASTLPRA SFETLLQHTN FMDGIKFVFF AFVVYSCFTI AVGWVVYEWK RKAHGCGKIP
     RYPHRDPFFG FDIVFGMAKS LRNDYFLVWL NKVHENLPKT FLVNFVGTRF IYTIEPENMK
     SMSAINWQDF AVGPMRRNNK ATAPFADKGV NTVDGHEWEF SRFLIKPFFK RETFTDTSRL
     TLHVDRVLEQ LPADGETVNI QPLIQRWFLD VTTASLFGES IESLVYPERA PICWAMVDVL
     RGLRLRLQWY KYLWLFRHQA WLDAVEVVHR YLNAHIDRTY KELDEYKRQG KNPEAADRND
     LLWYMASNLQ DKEALRSQIC LIFVPNNDTT SIFISHILWN LARHPGIYEK CRQEVLALGD
     AELSFSVLRN MKYLNAVLNE THRLFPNGVT QVRKCIRDTT LPVGGGPDGK QPIFVRKGDV
     VQVNKNVIHR DHDIWGPDAE DFRPERWENL RPYWNFVPFG GGPRRCPAQM LVTAEASYFL
     ARLMRVYKRI EARDPNPYVG VMRVGPSNKT GVHIALFKE