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KOJA_ASPOR
ID   KOJA_ASPOR              Reviewed;         428 AA.
AC   Q2U5I0;
DT   06-JUL-2016, integrated into UniProtKB/Swiss-Prot.
DT   24-JAN-2006, sequence version 1.
DT   03-AUG-2022, entry version 64.
DE   RecName: Full=Probable FAD-dependent monooxygenase kojA {ECO:0000305};
DE            EC=1.14.13.- {ECO:0000305|PubMed:20849972};
DE   AltName: Full=Kojic acid biosynthesis protein A {ECO:0000303|PubMed:21514215};
GN   Name=kojA {ECO:0000303|PubMed:21514215}; ORFNames=AO090113000136;
OS   Aspergillus oryzae (strain ATCC 42149 / RIB 40) (Yellow koji mold).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC   Aspergillus subgen. Circumdati.
OX   NCBI_TaxID=510516;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 42149 / RIB 40;
RX   PubMed=16372010; DOI=10.1038/nature04300;
RA   Machida M., Asai K., Sano M., Tanaka T., Kumagai T., Terai G., Kusumoto K.,
RA   Arima T., Akita O., Kashiwagi Y., Abe K., Gomi K., Horiuchi H.,
RA   Kitamoto K., Kobayashi T., Takeuchi M., Denning D.W., Galagan J.E.,
RA   Nierman W.C., Yu J., Archer D.B., Bennett J.W., Bhatnagar D.,
RA   Cleveland T.E., Fedorova N.D., Gotoh O., Horikawa H., Hosoyama A.,
RA   Ichinomiya M., Igarashi R., Iwashita K., Juvvadi P.R., Kato M., Kato Y.,
RA   Kin T., Kokubun A., Maeda H., Maeyama N., Maruyama J., Nagasaki H.,
RA   Nakajima T., Oda K., Okada K., Paulsen I., Sakamoto K., Sawano T.,
RA   Takahashi M., Takase K., Terabayashi Y., Wortman J.R., Yamada O.,
RA   Yamagata Y., Anazawa H., Hata Y., Koide Y., Komori T., Koyama Y.,
RA   Minetoki T., Suharnan S., Tanaka A., Isono K., Kuhara S., Ogasawara N.,
RA   Kikuchi H.;
RT   "Genome sequencing and analysis of Aspergillus oryzae.";
RL   Nature 438:1157-1161(2005).
RN   [2]
RP   BIOTECHNOLOGY.
RX   PubMed=7714722; DOI=10.1111/j.2042-7158.1994.tb03253.x;
RA   Cabanes J., Chazarra S., Garcia-Carmona F.;
RT   "Kojic acid, a cosmetic skin whitening agent, is a slow-binding inhibitor
RT   of catecholase activity of tyrosinase.";
RL   J. Pharm. Pharmacol. 46:982-985(1994).
RN   [3]
RP   REVIEW ON BIOTECHNOLOGY.
RX   PubMed=17119644; DOI=10.1039/b603758p;
RA   Bentley R.;
RT   "From miso, sake and shoyu to cosmetics: a century of science for kojic
RT   acid.";
RL   Nat. Prod. Rep. 23:1046-1062(2006).
RN   [4]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=20849972; DOI=10.1016/j.fgb.2010.08.014;
RA   Terabayashi Y., Sano M., Yamane N., Marui J., Tamano K., Sagara J.,
RA   Dohmoto M., Oda K., Ohshima E., Tachibana K., Higa Y., Ohashi S., Koike H.,
RA   Machida M.;
RT   "Identification and characterization of genes responsible for biosynthesis
RT   of kojic acid, an industrially important compound from Aspergillus
RT   oryzae.";
RL   Fungal Genet. Biol. 47:953-961(2010).
RN   [5]
RP   INDUCTION.
RX   PubMed=21897021; DOI=10.1271/bbb.110235;
RA   Oda K., Kobayashi A., Ohashi S., Sano M.;
RT   "Aspergillus oryzae laeA regulates kojic acid synthesis genes.";
RL   Biosci. Biotechnol. Biochem. 75:1832-1834(2011).
RN   [6]
RP   INDUCTION.
RX   PubMed=21514215; DOI=10.1016/j.jbiosc.2011.03.010;
RA   Marui J., Yamane N., Ohashi-Kunihiro S., Ando T., Terabayashi Y., Sano M.,
RA   Ohashi S., Ohshima E., Tachibana K., Higa Y., Nishimura M., Koike H.,
RA   Machida M.;
RT   "Kojic acid biosynthesis in Aspergillus oryzae is regulated by a
RT   Zn(II)(2)Cys(6) transcriptional activator and induced by kojic acid at the
RT   transcriptional level.";
RL   J. Biosci. Bioeng. 112:40-43(2011).
RN   [7]
RP   INDUCTION.
RX   PubMed=26657710; DOI=10.1016/j.jbiotec.2015.11.023;
RA   Liu J.M., Yu T.C., Lin S.P., Hsu R.J., Hsu K.D., Cheng K.C.;
RT   "Evaluation of kojic acid production in a repeated-batch PCS biofilm
RT   reactor.";
RL   J. Biotechnol. 218:41-48(2016).
RN   [8]
RP   BIOTECHNOLOGY.
RX   PubMed=27197670; DOI=10.4014/jmb.1603.03040;
RA   Kim T.Y., Jang J.Y., Jeon S.J., Lee H.W., Bae C.H., Yeo J.H., Lee H.B.,
RA   Kim I.S., Park H.W., Kim J.C.;
RT   "Nematicidal activity of kojic acid produced by Aspergillus oryzae against
RT   Meloidogyne incognita.";
RL   J. Microbiol. Biotechnol. 26:1383-1391(2016).
CC   -!- FUNCTION: Probable FAD-dependent monooxygenase; part of the gene
CC       cluster that mediates the biosynthesis of 5-hydroxy-2-hydroxymethyl-
CC       1,4-pyrone, also know as kojic acid, a by-product in the fermentation
CC       process of malting rice that acts as a chelation agent
CC       (PubMed:20849972). Glucose might be converted to kojic acid by a
CC       combination of dehydrogenase and dehydratase reactions involving kojA
CC       and probably additional enzymes (PubMed:20849972).
CC       {ECO:0000269|PubMed:20849972}.
CC   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000305};
CC   -!- INDUCTION: Expression is controlled by the kojic acid gene cluster
CC       transcription factor kojR (PubMed:21514215). Expression is also
CC       positively regulated by the secondary metabolism general regulator laeA
CC       (PubMed:21897021). Finally, nitrogen deficiency also positively
CC       regulates expression (PubMed:26657710). {ECO:0000269|PubMed:21514215,
CC       ECO:0000269|PubMed:21897021, ECO:0000269|PubMed:26657710}.
CC   -!- DISRUPTION PHENOTYPE: Leads to the loss of kojic acid production
CC       (PubMed:20849972). {ECO:0000269|PubMed:20849972}.
CC   -!- BIOTECHNOLOGY: Kojic acid can be used for several biotechnological
CC       applications, including use as an antibiotic, as an additive to prevent
CC       browning of food materials, and as an antioxidant (PubMed:17119644).
CC       Kojic acid is also interesting as an inhibitor of tyrosinase
CC       (PubMed:7714722). Finally, kojic acid has also been shown to have
CC       strong nematicidal activity (PubMed:27197670).
CC       {ECO:0000269|PubMed:17119644, ECO:0000269|PubMed:27197670,
CC       ECO:0000269|PubMed:7714722}.
CC   -!- SIMILARITY: Belongs to the aromatic-ring hydroxylase family.
CC       {ECO:0000305}.
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DR   EMBL; AP007166; BAE63185.1; -; Genomic_DNA.
DR   RefSeq; XP_001824318.1; XM_001824266.1.
DR   AlphaFoldDB; Q2U5I0; -.
DR   SMR; Q2U5I0; -.
DR   EnsemblFungi; BAE63185; BAE63185; AO090113000136.
DR   GeneID; 5995965; -.
DR   KEGG; aor:AO090113000136; -.
DR   VEuPathDB; FungiDB:AO090113000136; -.
DR   HOGENOM; CLU_565958_0_0_1; -.
DR   OMA; TIFFAHE; -.
DR   Proteomes; UP000006564; Chromosome 5.
DR   GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR   GO; GO:2001317; P:kojic acid biosynthetic process; IMP:GO_Central.
DR   Gene3D; 3.50.50.60; -; 1.
DR   InterPro; IPR006076; FAD-dep_OxRdtase.
DR   InterPro; IPR036188; FAD/NAD-bd_sf.
DR   Pfam; PF01266; DAO; 1.
DR   SUPFAM; SSF51905; SSF51905; 1.
PE   1: Evidence at protein level;
KW   FAD; Flavoprotein; Monooxygenase; Oxidoreductase; Reference proteome.
FT   CHAIN           1..428
FT                   /note="Probable FAD-dependent monooxygenase kojA"
FT                   /id="PRO_0000436873"
FT   BINDING         52..60
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:P20586"
FT   BINDING         257..259
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P20586"
FT   BINDING         328..329
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:P20586"
FT   SITE            421
FT                   /note="Important for catalytic activity"
FT                   /evidence="ECO:0000250|UniProtKB:P20586"
SQ   SEQUENCE   428 AA;  47791 MW;  A91E7B37C0957558 CRC64;
     MRVATQLRVG IVGGGWNGCH LALELKKQGH RVSLFEQKPD IFQGVSGNFG IRLHKGPHYP
     RSKATRDSCR EALVKFCETY PELVVHHESA IYAHGEADAL GNPSKVSDEA FRDVCYESPE
     CTAVDPKANG FQGLISAYNL DEPSVAIGDR LRNTFKEKLG RAGIYVHLNA TVDRIIHTED
     TNRIQTGDGQ YVFDVVINAT GYTSLLPQNI ADALPVDIGI TYQTCIALVY EDQQPQEKPL
     SFIVMDGWFP CVMPAIDTNE PLQKKYILTH GSYTILGSFD RHEEGQELLD SLDEEAIAAR
     IKPHCEREIT RFWPGFLDRF QYRGWKGSVL AKLKTTSEFR SSLTFEKDGV IHIFPGKVSN
     VVTAAEEVVP LINDIARRRH GVVREWNGVR FTVSSAFHTH SKEIGDKPGL GEHHTSNLQT
     YVSLVTAN
 
 
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