ID   ATNE_EMENI              Reviewed;         518 AA.
AC   Q5AUZ9; A0A1U8QUH5; C8V3Y6;
DT   23-MAY-2018, integrated into UniProtKB/Swiss-Prot.
DT   26-APR-2005, sequence version 1.
DT   03-AUG-2022, entry version 105.
DE   RecName: Full=Cytochrome P450 monooxygenase atnE {ECO:0000303|PubMed:26563584};
DE            EC=1.-.-.- {ECO:0000305|PubMed:26563584};
DE   AltName: Full=Aspercryptin biosynthesis cluster protein E {ECO:0000303|PubMed:26563584};
GN   Name=atnE {ECO:0000303|PubMed:26563584}; ORFNames=ANIA_07881;
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   IDENTIFICATION OF THE CLUSTER.
RX   PubMed=23248299; DOI=10.1073/pnas.1205532110;
RA   Andersen M.R., Nielsen J.B., Klitgaard A., Petersen L.M., Zachariasen M.,
RA   Hansen T.J., Blicher L.H., Gotfredsen C.H., Larsen T.O., Nielsen K.F.,
RA   Mortensen U.H.;
RT   "Accurate prediction of secondary metabolite gene clusters in filamentous
RT   fungi.";
RL   Proc. Natl. Acad. Sci. U.S.A. 110:E99-E107(2013).
RN   [4]
RP   FUNCTION, AND INDUCTION.
RX   PubMed=27310134; DOI=10.1021/acschembio.6b00398;
RA   Henke M.T., Soukup A.A., Goering A.W., McClure R.A., Thomson R.J.,
RA   Keller N.P., Kelleher N.L.;
RT   "New aspercryptins, lipopeptide natural products, revealed by HDAC
RT   inhibition in Aspergillus nidulans.";
RL   ACS Chem. Biol. 11:2117-2123(2016).
RN   [5]
RP   FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX   PubMed=26563584; DOI=10.1002/anie.201507097;
RA   Chiang Y.M., Ahuja M., Oakley C.E., Entwistle R., Asokan A., Zutz C.,
RA   Wang C.C., Oakley B.R.;
RT   "Development of genetic dereplication strains in Aspergillus nidulans
RT   results in the discovery of aspercryptin.";
RL   Angew. Chem. Int. Ed. 55:1662-1665(2016).
CC   -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC       mediates the biosynthesis of aspercryptins, linear lipopeptides built
CC       from six amino acids including 2 highly unusual and nonproteogenic
CC       amino acids, 2-amino-octanoic acid (2aoa) and 2-amino-dodecanol (2adol)
CC       (PubMed:23248299, PubMed:27310134, PubMed:26563584). The core structure
CC       of aspercryptins is as follows: Ser/Ala-Thr-Ile/Val-2aoa-Asn-2adol
CC       (PubMed:27310134). The first step of aspercryptin biosynthesis is the
CC       generation of the fatty acid precursors, octanoic and dodecanoic acids,
CC       by the FAS subunits atnF and atnM (PubMed:27310134, PubMed:26563584).
CC       The fatty acid precursors are likely transformed into the corresponding
CC       alpha-amino fatty acids in three steps (PubMed:27310134,
CC       PubMed:26563584). First, they are hydroxylated by the cytochrome P450
CC       monooxygenase atnE, then oxidized to the corresponding alpha-keto acids
CC       by the NAD(P)-dependent oxidoreductase atnD, and finally converted to
CC       the alpha-amino fatty acids by the PLP-dependent aminotransferases atnH
CC       or atnJ (PubMed:27310134, PubMed:26563584). the alpha-amino fatty
CC       acids, 2-amino-octanoic and 2-amino-dodecanoic acids, are recognized,
CC       activated, and covalently tethered to the NRPS atnA by its fourth and
CC       sixth adenylation domains (PubMed:27310134). The second module of atnA
CC       is the Thr module and contains an epimerase (E) domain responsible for
CC       the epimerization of Thr to D-allo-Thr (PubMed:26563584). Additionally,
CC       despite atnA having only one epimerase domain, the first amino acid of
CC       aspercryptin A1 is D-Ser, suggesting that serine is either loaded
CC       directly as D-Ser on the first module or that the epimerase domain in
CC       the threonine module epimerizes both L-Ser and L-Thr (PubMed:27310134).
CC       After condensation of the hexapeptide of aspercryptin, the C-terminal
CC       reductase (TE) domain might be involved in the reductive release and
CC       production of the aldehyde hexapeptide (PubMed:26563584). Further
CC       reduction would generate aspercryptins (PubMed:27310134,
CC       PubMed:26563584). The variety of aspercryptins produced reflects the
CC       flexibiliy of the atnA NRPS, allowing incorporation of alanine instead
CC       of serine, valine for isoleucine, and a C10 fatty amino alcohol instead
CC       of the C12 version (PubMed:27310134). AtnB seems to be involved in the
CC       selectivity for Ile versus Val by the third module (PubMed:26563584).
CC       Moreover, type B, C and D aspercryptins have an additional N-terminal
CC       cichorine, acetyl and propionyl group respectively (PubMed:27310134).
CC       {ECO:0000269|PubMed:23248299, ECO:0000269|PubMed:26563584,
CC       ECO:0000269|PubMed:27310134}.
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P04798};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:26563584}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC       protein {ECO:0000255}.
CC   -!- INDUCTION: Expression is positively regulated by the aspercryptin
CC       cluser-specific transcription factor atnN (PubMed:27310134).
CC       {ECO:0000269|PubMed:27310134}.
CC   -!- DISRUPTION PHENOTYPE: Abolishes the production of aspercryptin
CC       (PubMed:26563584). {ECO:0000269|PubMed:26563584}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; BN001302; CBF73446.1; -; Genomic_DNA.
DR   EMBL; AACD01000135; EAA59535.1; -; Genomic_DNA.
DR   RefSeq; XP_681150.1; XM_676058.1.
DR   AlphaFoldDB; Q5AUZ9; -.
DR   SMR; Q5AUZ9; -.
DR   STRING; 162425.CADANIAP00003897; -.
DR   EnsemblFungi; CBF73446; CBF73446; ANIA_07881.
DR   EnsemblFungi; EAA59535; EAA59535; AN7881.2.
DR   GeneID; 2869072; -.
DR   KEGG; ani:AN7881.2; -.
DR   VEuPathDB; FungiDB:AN7881; -.
DR   eggNOG; KOG0157; Eukaryota.
DR   HOGENOM; CLU_001570_14_11_1; -.
DR   InParanoid; Q5AUZ9; -.
DR   OMA; RHRASEY; -.
DR   OrthoDB; 1247045at2759; -.
DR   Proteomes; UP000000560; Chromosome II.
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: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: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; 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..518
FT                   /note="Cytochrome P450 monooxygenase atnE"
FT                   /id="PRO_0000444123"
FT   TRANSMEM        11..31
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         458
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        184
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ   SEQUENCE   518 AA;  58116 MW;  224FCBF4AD633C88 CRC64;
     MLPTYFGTSN FLAAFAVWMG VVVLAFAIFC VRRLYFHPYS KYPGPLLGKL TNYYAVYHSW
     KGDQHIDMWR CHEKYGPYVR YGPNELSINT AAGLKEIYSH GRNFKKSVKY NAMVHQAANT
     LTTIDKRKHG KKRRLISQAF SDAAFRSYEE TIQQKIAQLC TALRRRDDDS NEIVPDGNWG
     PAKNMSHWCD WFTFDVMCSV IFGVPWSSLT EKTYRNVPHL IEVSNVRVGC LIEAGGSKNM
     KIDKYLFPAA IAARNQFVKF VNDIIRQGMA MSAKGSLKGA FALLRDATDP ETQEPLSFKE
     LCGESATLVV AGTDTTSTAL AASIYYLCNH PKVYERAVQE VRSTFQSRAE IGLGPKVNSC
     TYLRAVIEES MRLSPSAPGP LWRQADAGGA TVDGQYIPQG LEAGTCVYAI QHHPEIYPQP
     FKFVPERWLG PEAVPEQYRS DYSPFAGFTP FSIGPRGCIG KPLAYIELTL TLCHILYAFD
     MRLPQGVNVN EDAEYQLALH ITAAKEGPLV EFRPRTVV