ATC_ASPTN
ID ATC_ASPTN Reviewed; 596 AA.
AC Q0CJ60;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 1.
DT 25-MAY-2022, entry version 72.
DE RecName: Full=Cyclase atC {ECO:0000303|PubMed:25265334};
DE EC=4.2.1.- {ECO:0000269|PubMed:25265334};
DE AltName: Full=Terreic acid biosynthesis cluster protein C {ECO:0000303|PubMed:25265334};
DE Flags: Precursor;
GN Name=atC {ECO:0000303|PubMed:25265334}; ORFNames=ATEG_06274;
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: Cyclase; part of the gene cluster that mediates the
CC biosynthesis of terreic acid, a quinone epoxide inhibitor of Bruton's
CC tyrosine kinase (PubMed:24534845, PubMed:25265334). The first step of
CC the pathway is the synthesis of 6-methylsalicylic acid (6-MSA) by the
CC 6-methylsalicylic acid synthase atX (PubMed:9003280, PubMed:9438344,
CC PubMed:25265334). In the biosynthesis of 6-MSA, atX utilizes one
CC acetyl-CoA and three malonyl-CoAs as its substrates and catalyzes a
CC series of programmed reactions including Claisen condensation,
CC dehydration, reduction, and cyclization to yield 6-MSA (PubMed:9003280,
CC PubMed:9438344, PubMed:25265334). The 6-methylsalicylic acid
CC decarboxylase atA then catalyzes the decarboxylative hydroxylation of
CC 6-MSA to 3-methylcatechol (PubMed:25265334). The next step is the
CC conversion of 3-methylcatechol to terremutin via several oxidation
CC steps involving the cytochrome P450 monooxygenase atE and probably also
CC the cytochrome P450 monooxygenase atG (PubMed:25265334). Lastly, atC is
CC required for the oxidation of terremutin to terreic acid
CC (PubMed:25265334). No function could be assigned to atD yet, although
CC it is involved in the biosynthesis of terreic acid (PubMed:25265334).
CC {ECO:0000269|PubMed:25265334, ECO:0000269|PubMed:9003280,
CC ECO:0000269|PubMed:9438344, ECO:0000305|PubMed:24534845}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:25265334}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of terreic acid, but
CC accumulates terremutin (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 GMC oxidoreductase family. {ECO:0000305}.
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DR EMBL; CH476602; EAU32818.1; -; Genomic_DNA.
DR RefSeq; XP_001215452.1; XM_001215452.1.
DR AlphaFoldDB; Q0CJ60; -.
DR SMR; Q0CJ60; -.
DR STRING; 341663.Q0CJ60; -.
DR EnsemblFungi; EAU32818; EAU32818; ATEG_06274.
DR GeneID; 4322098; -.
DR VEuPathDB; FungiDB:ATEG_06274; -.
DR eggNOG; KOG1238; Eukaryota.
DR HOGENOM; CLU_002865_6_3_1; -.
DR OMA; CAMGNSS; -.
DR OrthoDB; 798314at2759; -.
DR Proteomes; UP000007963; Unassembled WGS sequence.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR GO; GO:0016614; F:oxidoreductase activity, acting on CH-OH group of donors; IEA:InterPro.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR012132; GMC_OxRdtase.
DR InterPro; IPR000172; GMC_OxRdtase_N.
DR InterPro; IPR007867; GMC_OxRtase_C.
DR PANTHER; PTHR11552; PTHR11552; 1.
DR Pfam; PF05199; GMC_oxred_C; 1.
DR Pfam; PF00732; GMC_oxred_N; 1.
DR PIRSF; PIRSF000137; Alcohol_oxidase; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Lyase; Reference proteome; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..596
FT /note="Cyclase atC"
FT /evidence="ECO:0000255"
FT /id="PRO_0000437638"
FT CARBOHYD 43
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 69
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 87
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 280
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 358
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 408
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 411
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 542
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 596 AA; 63451 MW; 9830DC37EE86F8E9 CRC64;
MRVFPTYIAV SGLFGGAFAA FGATNIKGQT KLFGTSFGIL AKNASYDYVI VGGGTAGLTV
AARLAAQPNV SVAVIEAGSF YEIDNGNISQ VPGYGANYLS FNDLTPSPVL VDWGLITEPQ
DGLNNRQIHY SAGKTLGGRA TKGSYQRWAE LVDDDTYTWD KLLPYLKKSV DFTKPKDAAT
YPYDASVYSP EGGPLQVSFP NYRAPCDDFM ETAFTKSGLK PIKGLNSGHL DGFAPTTFVI
NPADQTRSSS EAAFLQEALD TTAMTLYLRT LAKKILFDTN KTANGVLVET NGAEYTISAK
KEVILSAGVF HSPQLLLLSG IGQADSLEKF GIPVISDLAG VGQNLWDHLF IFTSHEMNIT
TNSGVLVDPE LLAEAVESYL NQQTGPLTGI GGGVVGWEKL PNRVSFSNST NETLASFPDD
FPEVEYVALA PGSNPASDPL ANHFASVTAA VQSTSSRGYV KLRSADPHDA PIININALSH
PADADLAVGA IKRLRQIAEA TGVRVKEVLP GPEVVSDAEI LEWVRNNAVN GYHASSTCAM
GNSSNPDAVV DTRAKVYGVS NLRVVDASAL PYLPPGHPMS SIYAFAELIA EDILSK
