GEDA_ASPTN
ID GEDA_ASPTN Reviewed; 486 AA.
AC Q0CCY5;
DT 07-SEP-2016, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 1.
DT 03-AUG-2022, entry version 66.
DE RecName: Full=O-methyltransferase gedA {ECO:0000303|PubMed:24009710};
DE EC=2.1.1.283 {ECO:0000269|PubMed:1444712};
DE AltName: Full=Geodin synthesis protein A {ECO:0000303|PubMed:24009710};
GN Name=gedA {ECO:0000303|PubMed:24009710}; ORFNames=ATEG_08449;
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=3182756; DOI=10.1093/oxfordjournals.jbchem.a122365;
RA Fujii I., Ebizuka Y., Sankawa U.;
RT "A novel anthraquinone ring cleavage enzyme from Aspergillus terreus.";
RL J. Biochem. 103:878-883(1988).
RN [3]
RP FUNCTION.
RX PubMed=1810248;
RA Fujii I., Chen Z.G., Ebizuka Y., Sankawa U.;
RT "Identification of emodinanthrone oxygenase in fungus Aspergillus
RT terreus.";
RL Biochem. Int. 25:1043-1049(1991).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=1444712; DOI=10.1007/bf00249062;
RA Chen Z.G., Fujii I., Ebizuka Y., Sankawa U.;
RT "Emodin O-methyltransferase from Aspergillus terreus.";
RL Arch. Microbiol. 158:29-34(1992).
RN [5]
RP FUNCTION.
RX PubMed=7665560; DOI=10.1074/jbc.270.37.21495;
RA Huang K.X., Fujii I., Ebizuka Y., Gomi K., Sankawa U.;
RT "Molecular cloning and heterologous expression of the gene encoding
RT dihydrogeodin oxidase, a multicopper blue enzyme from Aspergillus
RT terreus.";
RL J. Biol. Chem. 270:21495-21502(1995).
RN [6]
RP BIOTECHNOLOGY.
RX PubMed=10819297; DOI=10.7164/antibiotics.53.262;
RA Shinohara C., Chikanishi T., Nakashima S., Hashimoto A., Hamanaka A.,
RA Endo A., Hasumi K.;
RT "Enhancement of fibrinolytic activity of vascular endothelial cells by
RT chaetoglobosin A, crinipellin B, geodin and triticone B.";
RL J. Antibiot. 53:262-268(2000).
RN [7]
RP FUNCTION.
RX PubMed=12536215; DOI=10.1038/nbt781;
RA Askenazi M., Driggers E.M., Holtzman D.A., Norman T.C., Iverson S.,
RA Zimmer D.P., Boers M.E., Blomquist P.R., Martinez E.J., Monreal A.W.,
RA Feibelman T.P., Mayorga M.E., Maxon M.E., Sykes K., Tobin J.V., Cordero E.,
RA Salama S.R., Trueheart J., Royer J.C., Madden K.T.;
RT "Integrating transcriptional and metabolite profiles to direct the
RT engineering of lovastatin-producing fungal strains.";
RL Nat. Biotechnol. 21:150-156(2003).
RN [8]
RP BIOTECHNOLOGY.
RX PubMed=16320762; DOI=10.1038/ja.2005.79;
RA Sato S., Okusa N., Ogawa A., Ikenoue T., Seki T., Tsuji T.;
RT "Identification and preliminary SAR studies of (+)-Geodin as a glucose
RT uptake stimulator for rat adipocytes.";
RL J. Antibiot. 58:583-589(2005).
RN [9]
RP FUNCTION.
RX PubMed=19549600; DOI=10.1016/j.chembiol.2009.04.004;
RA Awakawa T., Yokota K., Funa N., Doi F., Mori N., Watanabe H.,
RA Horinouchi S.;
RT "Physically discrete beta-lactamase-type thioesterase catalyzes product
RT release in atrochrysone synthesis by iterative type I polyketide
RT synthase.";
RL Chem. Biol. 16:613-623(2009).
RN [10]
RP FUNCTION.
RX PubMed=24009710; DOI=10.1371/journal.pone.0072871;
RA Nielsen M.T., Nielsen J.B., Anyaogu D.C., Holm D.K., Nielsen K.F.,
RA Larsen T.O., Mortensen U.H.;
RT "Heterologous reconstitution of the intact geodin gene cluster in
RT Aspergillus nidulans through a simple and versatile PCR based approach.";
RL PLoS ONE 8:E72871-E72871(2013).
CC -!- FUNCTION: O-methyltransferase; part of the gene cluster that mediates
CC the biosynthesis of geodin, an intermediate in the biosynthesis of
CC other natural products (PubMed:7665560, PubMed:19549600,
CC PubMed:24009710). The pathway begins with the synthesis of atrochrysone
CC thioester by the polyketide synthase (PKS) gedC (PubMed:12536215,
CC PubMed:19549600). The atrochrysone carboxyl ACP thioesterase gedB then
CC breaks the thioester bond and releases the atrochrysone carboxylic acid
CC from gedC (PubMed:19549600). The atrochrysone carboxylic acid is then
CC converted to atrochrysone which is further transformed into
CC emodinanthrone (PubMed:24009710). The next step is performed by the
CC emodinanthrone oxygenase gedH that catalyzes the oxidation of
CC emodinanthrone to emodin (PubMed:1810248). Emodin O-methyltransferase
CC encoded probably by gedA then catalyzes methylation of the 8-hydroxy
CC group of emodin to form questin (PubMed:1444712). Ring cleavage of
CC questin by questin oxidase gedK leads to desmethylsulochrin via several
CC intermediates including questin epoxide (PubMed:3182756). Another
CC methylation step probably catalyzed by methyltransferase gedG leads to
CC the formation of sulochrin which is further converted to dihydrogeodin
CC by the sulochrin halogenase gedL (PubMed:24009710). Finally, the
CC dihydrogeodin oxidase gedJ catalyzes the stereospecific phenol
CC oxidative coupling reaction converting dihydrogeodin to geodin
CC (PubMed:7665560). {ECO:0000269|PubMed:12536215,
CC ECO:0000269|PubMed:1444712, ECO:0000269|PubMed:1810248,
CC ECO:0000269|PubMed:19549600, ECO:0000269|PubMed:24009710,
CC ECO:0000269|PubMed:3182756, ECO:0000269|PubMed:7665560}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=emodin + S-adenosyl-L-methionine = H(+) + questin + S-
CC adenosyl-L-homocysteine; Xref=Rhea:RHEA:36643, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57676, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:77659; EC=2.1.1.283;
CC Evidence={ECO:0000269|PubMed:1444712};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36644;
CC Evidence={ECO:0000269|PubMed:1444712};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.34 uM for emodin {ECO:0000269|PubMed:1444712};
CC KM=4.1 uM for S-adenosyl-l-methionine (SAM)
CC {ECO:0000269|PubMed:1444712};
CC pH dependence:
CC Optimum pH is 7.0-8.0. {ECO:0000269|PubMed:1444712};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:24009710}.
CC -!- BIOTECHNOLOGY: Geodin shows the glucose uptake stimulator activity
CC towards rat adipocytes (PubMed:16320762). Geodin also enhances the
CC fibrinolytic activity of vascular endothelial cells (PubMed:10819297).
CC {ECO:0000269|PubMed:10819297, ECO:0000269|PubMed:16320762}.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. Cation-independent O-methyltransferase family.
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DR EMBL; CH476605; EAU31622.1; -; Genomic_DNA.
DR RefSeq; XP_001217070.1; XM_001217070.1.
DR AlphaFoldDB; Q0CCY5; -.
DR SMR; Q0CCY5; -.
DR EnsemblFungi; EAU31622; EAU31622; ATEG_08449.
DR GeneID; 4353099; -.
DR VEuPathDB; FungiDB:ATEG_08449; -.
DR eggNOG; KOG3178; Eukaryota.
DR HOGENOM; CLU_005533_0_1_1; -.
DR OMA; CRGLVWI; -.
DR OrthoDB; 817726at2759; -.
DR BioCyc; MetaCyc:MON-17513; -.
DR SABIO-RK; Q0CCY5; -.
DR Proteomes; UP000007963; Unassembled WGS sequence.
DR GO; GO:0008171; F:O-methyltransferase activity; IEA:InterPro.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR016461; COMT-like.
DR InterPro; IPR001077; O_MeTrfase_dom.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF00891; Methyltransf_2; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS51683; SAM_OMT_II; 1.
PE 1: Evidence at protein level;
KW Methyltransferase; Reference proteome; S-adenosyl-L-methionine;
KW Transferase.
FT CHAIN 1..486
FT /note="O-methyltransferase gedA"
FT /id="PRO_0000437065"
FT ACT_SITE 373
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01020"
FT BINDING 298..299
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:O04385"
FT BINDING 321
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01020"
FT BINDING 353..354
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:O04385"
FT BINDING 369
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:O04385"
SQ SEQUENCE 486 AA; 53916 MW; 9F6B4B1F2FDB3961 CRC64;
MERQPKSLSD AVQLLQTTEI ISKCTQTIIA EWSNEAETFK KRASSGRAGA ELVLPSHELF
NAQRTITAAI GKLIELVSEP SVRILEIAGQ YQESRALYIA VERRIPDILA SQDNEGGMPV
KELSSRTGIE YRKLSRILRY LCSMGTFRQV GPDVFANNTI SACLVANEPL RAYVRLTGSE
AFTASDRLPK TLLDPSTGPS YDVTRTAWQD AIGTTKPRWE WIEERVEPDK LLDSGYHYPG
IPSLILEPQP PGEDGLVARP ELEIMGLAMV GGGRVFGAAH VFDFPWASLD NALVVDVGGG
VGGFALQLSK VYPDLRFVIQ DRGPVIQQAL ESVWPNENPA ALKDQRVQFM EHSFFDKNPV
EGADVYYLRY VLHDWSDDYC VNILSHIRES MAPHSRLLIC EQVMNTTIGD PDLTSAPAPL
PANYGFHARF SHSRDLTMMA AINGIERTPE EFKTILKSAG LALKQIWECR SQVSLLEAVR
ADARTA
