ID   ATG_ASPTN               Reviewed;         129 AA.
AC   Q0CJ54;
DT   02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT   17-OCT-2006, sequence version 1.
DT   03-AUG-2022, entry version 58.
DE   RecName: Full=Cytochrome P450 monooxygenase atG {ECO:0000303|PubMed:25265334};
DE            EC=1.-.-.- {ECO:0000269|PubMed:25265334};
DE   AltName: Full=Terreic acid biosynthesis cluster protein G {ECO:0000303|PubMed:25265334};
GN   Name=atG {ECO:0000303|PubMed:25265334}; ORFNames=ATEG_06280;
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 (BTK) (PubMed:24534845, PubMed:25265334).
CC       The first step of the pathway is the synthesis of 6-methylsalicylic
CC       acid (6-MSA) by the 6-methylsalicylic acid synthase atX
CC       (PubMed:9003280, PubMed:9438344, PubMed:25265334). In the biosynthesis
CC       of 6-MSA, atX utilizes one acetyl-CoA and three malonyl-CoAs as its
CC       substrates and catalyzes a series of programmed reactions including
CC       Claisen condensation, dehydration, reduction, and cyclization to yield
CC       6-MSA (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
CC       (PubMed:25265334). {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; EAU32824.1; -; Genomic_DNA.
DR   RefSeq; XP_001215458.1; XM_001215458.1.
DR   AlphaFoldDB; Q0CJ54; -.
DR   STRING; 33178.CADATEAP00007930; -.
DR   EnsemblFungi; EAU32824; EAU32824; ATEG_06280.
DR   GeneID; 4322429; -.
DR   VEuPathDB; FungiDB:ATEG_06280; -.
DR   eggNOG; KOG0159; Eukaryota.
DR   HOGENOM; CLU_001570_19_1_1; -.
DR   OMA; LAYCEIN; -.
DR   OrthoDB; 1888657at2759; -.
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..129
FT                   /note="Cytochrome P450 monooxygenase atG"
FT                   /id="PRO_0000437642"
FT   BINDING         69
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   129 AA;  14741 MW;  DE65716988A9584B CRC64;
     MTALQQFSRD GTFLSEALQT PISMNIWNTH YNKDFFPGPT EFWPERWMGE GTRELEKYLV
     PFGSGSRMCT GQNLSIAEQV LTIATLFRNY ELELYQTTKK NVVMASYCMI SLPGSESPGI
     QVKVRKTVQ