ID   TPZB_ASPTN              Reviewed;         375 AA.
AC   Q0CG33;
DT   02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT   17-OCT-2006, sequence version 1.
DT   03-AUG-2022, entry version 55.
DE   RecName: Full=Indoleamine 2,3-dioxygenase tpzB {ECO:0000303|PubMed:32843555};
DE            Short=IDO tpzB {ECO:0000303|PubMed:32843555};
DE            EC=1.13.11.52 {ECO:0000269|PubMed:32843555};
DE   AltName: Full=Terreazepine biosynthesis cluster protein B {ECO:0000303|PubMed:32843555};
GN   Name=tpzB {ECO:0000303|PubMed:32843555}; ORFNames=ATEG_07359;
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, CATALYTIC ACTIVITY, AND PATHWAY.
RX   PubMed=32843555; DOI=10.1128/mbio.01691-20;
RA   Caesar L.K., Robey M.T., Swyers M., Islam M.N., Ye R., Vagadia P.P.,
RA   Schiltz G.E., Thomas P.M., Wu C.C., Kelleher N.L., Keller N.P., Bok J.W.;
RT   "Heterologous expression of the unusual terreazepine biosynthetic gene
RT   cluster reveals a promising approach for identifying new chemical
RT   scaffolds.";
RL   MBio 11:0-0(2020).
CC   -!- FUNCTION: Indoleamine 2,3-dioxygenase; part of the gene cluster that
CC       mediates the biosynthesis of terreazepine, (PubMed:32843555). The first
CC       step of terreazepine biosynthesis is catalyzed by the indoleamine 2,3-
CC       dioxygenase tpzB which produces N-formyl-kynurenine through the
CC       catabolism of tryptophan (PubMed:32843555). The two-module NRPS tpzA
CC       then utilizes anthranilate and kynurenine to assemble terreazepine
CC       (PubMed:32843555). The first adenylation domain of tpzA (A1) loads
CC       anthranilate onto the T1 domain, while A2 loads kynurenine, generated
CC       through spontaneous nonenzymatic deformylation of the tzpB-supplied N-
CC       formyl-kynurenine (PubMed:32843555). TpzA produces a 2:1 mixture of S-R
CC       enantiomers, which suggests that the A2 domain accepts both D- and L-
CC       kynurenine (PubMed:32843555). The peptide bond formation between the
CC       tethered amino acids is catalyzed by the first condensation domain (C1)
CC       between anthranilate's carbonyl carbon and kynurenine's aliphatic
CC       primary amine (PubMed:32843555). The second C domain (C2) catalyzes the
CC       final cyclization event between the aromatic amine of kynurenine and
CC       the tethered carbonyl carbon, yielding the final terreazepine product
CC       (PubMed:32843555). The T3 domain may facilitate the interaction with
CC       downstream tailoring enzymes (PubMed:32843555).
CC       {ECO:0000269|PubMed:32843555}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=D-tryptophan + O2 = N-formyl-D-kynurenine;
CC         Xref=Rhea:RHEA:14189, ChEBI:CHEBI:15379, ChEBI:CHEBI:57719,
CC         ChEBI:CHEBI:60051; EC=1.13.11.52;
CC         Evidence={ECO:0000250|UniProtKB:P14902};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-tryptophan + O2 = N-formyl-L-kynurenine;
CC         Xref=Rhea:RHEA:24536, ChEBI:CHEBI:15379, ChEBI:CHEBI:57912,
CC         ChEBI:CHEBI:58629; EC=1.13.11.52;
CC         Evidence={ECO:0000250|UniProtKB:P14902};
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P14902};
CC       Note=Binds 1 heme group per subunit. {ECO:0000250|UniProtKB:P14902};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:32843555}.
CC   -!- SIMILARITY: Belongs to the indoleamine 2,3-dioxygenase family.
CC       {ECO:0000305}.
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DR   EMBL; CH476603; EAU32743.1; -; Genomic_DNA.
DR   RefSeq; XP_001210045.1; XM_001210045.1.
DR   AlphaFoldDB; Q0CG33; -.
DR   SMR; Q0CG33; -.
DR   STRING; 341663.Q0CG33; -.
DR   EnsemblFungi; EAU32743; EAU32743; ATEG_07359.
DR   GeneID; 4319034; -.
DR   VEuPathDB; FungiDB:ATEG_07359; -.
DR   eggNOG; ENOG502QV6W; Eukaryota.
DR   HOGENOM; CLU_010089_0_1_1; -.
DR   OMA; CHLLERM; -.
DR   OrthoDB; 1206249at2759; -.
DR   Proteomes; UP000007963; Unassembled WGS sequence.
DR   GO; GO:0020037; F:heme binding; IEA:InterPro.
DR   GO; GO:0033754; F:indoleamine 2,3-dioxygenase activity; IEA:UniProtKB-EC.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0019441; P:tryptophan catabolic process to kynurenine; IEA:InterPro.
DR   InterPro; IPR000898; Indolamine_dOase.
DR   InterPro; IPR037217; Trp/Indoleamine_2_3_dOase-like.
DR   PANTHER; PTHR28657; PTHR28657; 1.
DR   Pfam; PF01231; IDO; 1.
DR   SUPFAM; SSF140959; SSF140959; 1.
DR   PROSITE; PS00876; IDO_1; 1.
PE   1: Evidence at protein level;
KW   Dioxygenase; Heme; Iron; Metal-binding; Oxidoreductase; Reference proteome.
FT   CHAIN           1..375
FT                   /note="Indoleamine 2,3-dioxygenase tpzB"
FT                   /id="PRO_0000452967"
FT   BINDING         311
FT                   /ligand="heme"
FT                   /ligand_id="ChEBI:CHEBI:30413"
FT                   /ligand_part="Fe"
FT                   /ligand_part_id="ChEBI:CHEBI:18248"
FT                   /note="proximal binding residue"
FT                   /evidence="ECO:0000250|UniProtKB:P14902"
SQ   SEQUENCE   375 AA;  42348 MW;  E10DD3D5E87C0950 CRC64;
     MSTISDIKLE DYWISPRLGF LSDQPVLTEL PNPYYRCWEQ MISSVLPTDG WVLIRRQIDQ
     MPLLSTKKLH TEPEWRRAYT LLTTLAQVYI WGEANPSDKL PRSVAVPLRE VSEHLRISPC
     ASFASFCLWN VAPVPGVVPT DPDAYDPDNL HIINSFTGTK DEEWFFVISA SIEATGGRII
     ARMLEAVEAV HHDRIHVVNE FLNELASCIA EICHLLERMY EKCNPSVFCH RLRRFFSGSK
     AKEDAGLPRG VFYEGTDGGG DWLQYCGGSN AQSSLIQLFD IILGVKQSGP GIRRACTSFH
     QEMRQYMPGP HRDFLAQMEK LSNVRSYVLS HPRHSNLHNS YDQAVAALAL LRQKHMIVAS
     RLPHPLAIMA STISG