NANC_ASPNN
ID NANC_ASPNN Reviewed; 410 AA.
AC A0A6G9KIF9;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 12-AUG-2020, sequence version 1.
DT 03-AUG-2022, entry version 8.
DE RecName: Full=Indoleamine 2,3-dioxygenase nanC {ECO:0000303|PubMed:32182055};
DE Short=IDO nanC {ECO:0000303|PubMed:32182055};
DE EC=1.13.11.52 {ECO:0000269|PubMed:32182055};
DE AltName: Full=Nanangelenin A biosynthesis cluster protein C {ECO:0000303|PubMed:32182055};
GN Name=nanC {ECO:0000303|PubMed:32182055}; ORFNames=FE257_001450;
OS Aspergillus nanangensis.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus.
OX NCBI_TaxID=2582783;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, AND
RP PATHWAY.
RC STRAIN=CBS 146238 / FRR 6048 / MST FP2251;
RX PubMed=32182055; DOI=10.1021/jacs.0c01605;
RA Li H., Gilchrist C.L.M., Phan C.S., Lacey H.J., Vuong D., Moggach S.A.,
RA Lacey E., Piggott A.M., Chooi Y.H.;
RT "Biosynthesis of a new benzazepine alkaloid nanangelenin A from Aspergillus
RT nanangensis involves an unusual l-kynurenine-incorporating NRPS catalyzing
RT regioselective lactamization.";
RL J. Am. Chem. Soc. 142:7145-7152(2020).
CC -!- FUNCTION: Indoleamine 2,3-dioxygenase; part of the gene cluster that
CC mediates the biosynthesis of the benzazepine alkaloid nanangelenin A
CC which contains an unprecedented 3,4-dihydro-1-benzazepine-2,5-dione-N-
CC prenyl-N-acetoxy-anthranilamide scaffold (PubMed:32182055). The first
CC step of nanangelenin biosynthesis is catalyzed by the indoleamine 2,3-
CC dioxygenase nanC which produces N-formyl-kynurenine through the
CC catabolism of tryptophan (PubMed:32182055). The two-module NRPS nanA
CC then utilizes anthranilate (Ant) and L-kynurenine (L-Kyn) to assemble
CC the dipeptide product nanangelenin B (PubMed:32182055). The first
CC adenylation domain of nanA (A1) loads anthranilate onto the T1 domain,
CC while A2 loads kynurenine, generated through spontaneous nonenzymatic
CC deformylation of the nanC-supplied N-formyl-kynurenine
CC (PubMed:32182055). The peptide bond formation between the tethered
CC amino acids is catalyzed by the first condensation domain (C1) between
CC anthranilate's carbonyl carbon and kynurenine's aliphatic primary amine
CC (PubMed:32182055). The second C domain (C2) catalyzes the final
CC cyclization event between the aromatic amine of kynurenine and the
CC tethered carbonyl carbon, yielding nanangelenin B (PubMed:32182055).
CC The terminal T3 domain enhances the catalytic efficiency of C2,
CC suggesting the T2-tethered Ant-L-Kyn is transferred to T3 prior to
CC cyclization by C2 (PubMed:32182055). Once released from nanA,
CC nanangelenin B is then prenylated by the prenyltransferase nanD to form
CC nanangelenin C (PubMed:32182055). Nanangelenin C is then N-hydroxylated
CC by the FAD-dependent monooxygenase nanF and further acetylated by the
CC acetyltransferase nanB to yield nanangelenin F (PubMed:32182055).
CC Finally, the N-methyltransferase nanE methylates the amide nitrogen of
CC 1-benzazepine to convert nanangelenin F into nanangelenin A
CC (PubMed:32182055). NanE is also able to methylate most of the
CC intermediates of the pathway such as nanangelenin B and nanangelenin C
CC to produce nanangelenin D and nanangelenin E, respectively
CC (PubMed:32182055). {ECO:0000269|PubMed:32182055}.
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:32182055}.
CC -!- SIMILARITY: Belongs to the indoleamine 2,3-dioxygenase family.
CC {ECO:0000305}.
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DR EMBL; MT024570; QIQ51363.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A6G9KIF9; -.
DR SMR; A0A6G9KIF9; -.
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; 2.
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.
FT CHAIN 1..410
FT /note="Indoleamine 2,3-dioxygenase nanC"
FT /id="PRO_0000452966"
FT BINDING 309
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 410 AA; 46457 MW; 23829370DB13B748 CRC64;
MLSPVEVDLE AYDISRVSGF LPDKCPLRKL PDPYYVPWER LTAHLEPLIR AKRLQHELDQ
MPVLGITRLT SQPMRRRAYV LLSFLAQAYL WGEDIPNTTL PQAIAKPLTE VSTLLEIKPF
ATFAAFCLWS FSVHFDDDIG GDCHKFLDNM SMTCSFTGTT DEAWFFNVST AIEARGGRII
PSILNAISAV QNNDMLTVEG FLLDFTICLR DLCDLIDRMH ENCRPSVFYH RIRPFLSGTS
NNNPATENSK GVFYVQAEDG TGEWHRYSGG SNAQSSLIQL FDITLGINHD IGYKTRYLRE
MRSYMPAQHR RFLARMEEIS NLRPYALSHG PGSSNMCSLY NSAVLGLKNL RDKHMALVFR
YIIIPRAKEK AGNGLAIRQK DLVGTGGTDM IPFLRETRDD TMNAVHLPYS
