ATE_ASPTN
ID ATE_ASPTN Reviewed; 467 AA.
AC Q0CJ57;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 1.
DT 03-AUG-2022, entry version 66.
DE RecName: Full=Cytochrome P450 monooxygenase atE {ECO:0000303|PubMed:25265334};
DE EC=1.-.-.- {ECO:0000269|PubMed:25265334};
DE AltName: Full=Terreic acid biosynthesis cluster protein E {ECO:0000303|PubMed:25265334};
GN Name=atE {ECO:0000303|PubMed:25265334}; ORFNames=ATEG_06277;
OS Aspergillus terreus (strain NIH 2624 / FGSC A1156).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=341663;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NIH 2624 / FGSC A1156;
RA Birren B.W., Lander E.S., Galagan J.E., Nusbaum C., Devon K., Henn M.,
RA Ma L.-J., Jaffe D.B., Butler J., Alvarez P., Gnerre S., Grabherr M.,
RA Kleber M., Mauceli E.W., Brockman W., Rounsley S., Young S.K., LaButti K.,
RA Pushparaj V., DeCaprio D., Crawford M., Koehrsen M., Engels R.,
RA Montgomery P., Pearson M., Howarth C., Larson L., Luoma S., White J.,
RA Alvarado L., Kodira C.D., Zeng Q., Oleary S., Yandava C., Denning D.W.,
RA Nierman W.C., Milne T., Madden K.;
RT "Annotation of the Aspergillus terreus NIH2624 genome.";
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION.
RX PubMed=9003280; DOI=10.1007/s004380050289;
RA Fujii I., Ono Y., Tada H., Gomi K., Ebizuka Y., Sankawa U.;
RT "Cloning of the polyketide synthase gene atX from Aspergillus terreus and
RT its identification as the 6-methylsalicylic acid synthase gene by
RT heterologous expression.";
RL Mol. Gen. Genet. 253:1-10(1996).
RN [3]
RP FUNCTION.
RX PubMed=9438344; DOI=10.1007/bf02826548;
RA Pazoutova S., Linka M., Storkova S., Schwab H.;
RT "Polyketide synthase gene pksM from Aspergillus terreus expressed during
RT growth phase.";
RL Folia Microbiol. (Praha) 42:419-430(1997).
RN [4]
RP BIOTECHNOLOGY.
RX PubMed=10051623; DOI=10.1073/pnas.96.5.2227;
RA Kawakami Y., Hartman S.E., Kinoshita E., Suzuki H., Kitaura J., Yao L.,
RA Inagaki N., Franco A., Hata D., Maeda-Yamamoto M., Fukamachi H., Nagai H.,
RA Kawakami T.;
RT "Terreic acid, a quinone epoxide inhibitor of Bruton's tyrosine kinase.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:2227-2232(1999).
RN [5]
RP BIOTECHNOLOGY.
RX PubMed=23686727; DOI=10.1002/jobm.201200617;
RA Olesen S.H., Ingles D.J., Yang Y., Schoenbrunn E.;
RT "Differential antibacterial properties of the MurA inhibitors terreic acid
RT and fosfomycin.";
RL J. Basic Microbiol. 54:322-326(2014).
RN [6]
RP FUNCTION.
RX PubMed=24534845; DOI=10.1016/j.jbiotec.2014.01.038;
RA Boruta T., Bizukojc M.;
RT "Culture-based and sequence-based insights into biosynthesis of secondary
RT metabolites by Aspergillus terreus ATCC 20542.";
RL J. Biotechnol. 175:53-62(2014).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25265334; DOI=10.1021/ol502242a;
RA Guo C.J., Sun W.W., Bruno K.S., Wang C.C.;
RT "Molecular genetic characterization of terreic acid pathway in Aspergillus
RT terreus.";
RL Org. Lett. 16:5250-5253(2014).
CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of terreic acid, a quinone epoxide inhibitor
CC of Bruton's tyrosine kinase (PubMed:24534845, PubMed:25265334). The
CC first step of the pathway is the synthesis of 6-methylsalicylic acid
CC (6-MSA) by the 6-methylsalicylic acid synthase atX (PubMed:9003280,
CC PubMed:9438344, PubMed:25265334). In the biosynthesis of 6-MSA, atX
CC utilizes one acetyl-CoA and three malonyl-CoAs as its substrates and
CC catalyzes a series of programmed reactions including Claisen
CC condensation, dehydration, reduction, and cyclization to yield 6-MSA
CC (PubMed:9003280, PubMed:9438344, PubMed:25265334). The 6-
CC methylsalicylic acid decarboxylase atA then catalyzes the
CC decarboxylative hydroxylation of 6-MSA to 3-methylcatechol
CC (PubMed:25265334). The next step is the conversion of 3-methylcatechol
CC to terremutin via several oxidation steps involving the cytochrome P450
CC monooxygenase atE and probably also the cytochrome P450 monooxygenase
CC atG (PubMed:25265334). Lastly, atC is required for the oxidation of
CC terremutin to terreic acid (PubMed:25265334). No function could be
CC assigned to atD yet, although it is involved in the biosynthesis of
CC terreic acid (PubMed:25265334). {ECO:0000269|PubMed:25265334,
CC ECO:0000269|PubMed:9003280, ECO:0000269|PubMed:9438344,
CC ECO:0000305|PubMed:24534845}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:25265334}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of terreic acid, but
CC accumulates (2Z,4E)-2-methyl-2,4-hexadienedioic acid, a degradation
CC product of 3-methylcatechol (PubMed:25265334).
CC {ECO:0000269|PubMed:25265334}.
CC -!- BIOTECHNOLOGY: Terreic acid is a metabolite with antibiotic properties
CC (PubMed:23686727). Terric acid acts also as a selective inhibitor of
CC human Bruton's tyrosine kinase in mast cells and other immune cells
CC (PubMed:10051623). {ECO:0000269|PubMed:10051623,
CC ECO:0000269|PubMed:23686727}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; CH476602; EAU32821.1; -; Genomic_DNA.
DR RefSeq; XP_001215455.1; XM_001215455.1.
DR AlphaFoldDB; Q0CJ57; -.
DR SMR; Q0CJ57; -.
DR EnsemblFungi; EAU32821; EAU32821; ATEG_06277.
DR GeneID; 4322101; -.
DR KEGG; ag:EAU32821; -.
DR VEuPathDB; FungiDB:ATEG_06277; -.
DR eggNOG; KOG0156; Eukaryota.
DR HOGENOM; CLU_001570_2_1_1; -.
DR OMA; ALHWIVL; -.
DR OrthoDB; 702827at2759; -.
DR Proteomes; UP000007963; Unassembled WGS sequence.
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; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR SUPFAM; SSF48264; SSF48264; 1.
PE 1: Evidence at protein level;
KW Heme; Iron; Metal-binding; Monooxygenase; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..467
FT /note="Cytochrome P450 monooxygenase atE"
FT /id="PRO_0000437639"
FT BINDING 387
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"
SQ SEQUENCE 467 AA; 53877 MW; 98F88D661ABD5F3F CRC64;
MSKWAKQYGG IFSLKRFRNT TIVLTDWKIM KELVDKKSTN FSHRPPSKVA DLITRGNHIL
MMQYGETWRT MRKLIHQYLM ESQCEKEHWK VQEAEAAQML HDFLVDPENH MKHPKRYSNS
ITMSLVFGIR AKSVNDEYMT RLYSLMEKWS LVLETGATPP VDSWPLLQWI PERFMGYWRR
RATEVGDLMT GLYTEVLHVI ENRRKAGIYK DSLMDRVLDK KDKYRFDEHQ LAFLGGTLME
GGSDTSSSLI LAIVQAMTQY PEVQKKAHAE IDSVIGTDRS PAWSDFRKLP YINMMIKEAH
RWRPVLPLGV VHGLATDDSY NGMHLPKHST VILNVWGMHM DPDRFENPDA FIPERYANFP
ELAPHYAALA DGAARDHFGY GAGRRICPGI HLAERNLFIA VAKLLWAFEF KNNPAGKNDA
SAETGSSQGF MHCVKDYDAI VTVRGEERRQ TILRELEQAQ TVFAKYD
