ATA_ASPTN
ID ATA_ASPTN Reviewed; 442 AA.
AC Q0CJ62;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 1.
DT 03-AUG-2022, entry version 68.
DE RecName: Full=6-methylsalicylic acid decarboxylase atA {ECO:0000303|PubMed:25265334};
DE EC=1.-.-.- {ECO:0000269|PubMed:25265334};
DE AltName: Full=FAD-dependent monooxygenase atA {ECO:0000305};
DE AltName: Full=Terreic acid biosynthesis cluster protein A {ECO:0000303|PubMed:25265334};
GN Name=atA {ECO:0000303|PubMed:25265334}; ORFNames=ATEG_06272;
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: 6-methylsalicylic acid decarboxylase; part of the gene
CC cluster that mediates the biosynthesis of terreic acid, a quinone
CC epoxide inhibitor of Bruton's tyrosine kinase (PubMed:24534845,
CC PubMed:25265334). The first step of the pathway is the synthesis of 6-
CC methylsalicylic 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=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000305};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:25265334}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of terreic acid, but
CC accumulates 6-methylsalicylic acid (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 BTK 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 paxM FAD-dependent monooxygenase family.
CC {ECO:0000305}.
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DR EMBL; CH476602; EAU32816.1; -; Genomic_DNA.
DR RefSeq; XP_001215450.1; XM_001215450.1.
DR AlphaFoldDB; Q0CJ62; -.
DR SMR; Q0CJ62; -.
DR STRING; 341663.Q0CJ62; -.
DR EnsemblFungi; EAU32816; EAU32816; ATEG_06272.
DR GeneID; 4322129; -.
DR VEuPathDB; FungiDB:ATEG_06272; -.
DR eggNOG; KOG2614; Eukaryota.
DR HOGENOM; CLU_009665_6_3_1; -.
DR OMA; SAHACAP; -.
DR OrthoDB; 521070at2759; -.
DR Proteomes; UP000007963; Unassembled WGS sequence.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR002938; FAD-bd.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR Pfam; PF01494; FAD_binding_3; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 1: Evidence at protein level;
KW FAD; Flavoprotein; Glycoprotein; Membrane; Monooxygenase; Oxidoreductase;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..442
FT /note="6-methylsalicylic acid decarboxylase atA"
FT /id="PRO_0000437636"
FT TRANSMEM 7..27
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 17
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 37..38
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 240..242
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 307
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 317..321
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT CARBOHYD 107
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 442 AA; 48456 MW; 4F7F4045C3A7391F CRC64;
MTFSNRVSVA IIGGGIGGLS LAIGLLQNKN LDVAIYETAP KFAEIGAGVA LGPNAQHALA
LISPAAEHAF RIHATTSLSP EFEHVWFDFR NGNAGEKDGE VLSKVENETG QQTVHRAKFL
DELVKLIPRE IAHFGKRLIH IQKDPVSGGA QYKLFFEDGT TASADCVIGA DGIHSSVRKH
LLGESHPAAT PVFTGTVVYR GLIPMDVARD AIGEFADNSY MWCGDGGMVM TYPIDHGETL
NVVGTRNDKG RWDGPPYTRP VDEETVRNDF MGWGEIPSKV IQPTMWAILD HYPAPYYYSG
NVAIMGDAAH ATTPFQGAGA GQAIEDALVL STLFQRVTHS GLVRPALAAY NNVRLRRTQK
VVATSRDALR LFCFNDRYVD GDAQRWREVW NGRMDWLWGM DLEKQNRDAV NLFADIVEKQ
SSARETMPKF GPVPFPVATS TV
