ID   NANE_ASPNN              Reviewed;         405 AA.
AC   A0A6G9KJC3;
DT   02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT   12-AUG-2020, sequence version 1.
DT   03-AUG-2022, entry version 7.
DE   RecName: Full=N-methyltransferase nanE {ECO:0000303|PubMed:32182055};
DE            EC=2.1.1.- {ECO:0000269|PubMed:32182055};
DE   AltName: Full=Nanangelenin A biosynthesis cluster protein E {ECO:0000303|PubMed:32182055};
GN   Name=nanE {ECO:0000303|PubMed:32182055}; ORFNames=FE257_001453;
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, AND 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: N-methyltransferase; part of the gene cluster that mediates
CC       the biosynthesis of the benzazepine alkaloid nanangelenin A which
CC       contains an unprecedented 3,4-dihydro-1-benzazepine-2,5-dione-N-prenyl-
CC       N-acetoxy-anthranilamide scaffold (PubMed:32182055). The first step of
CC       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   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:32182055}.
CC   -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC       superfamily. Cation-independent O-methyltransferase family.
CC       {ECO:0000305}.
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DR   EMBL; MT024570; QIQ51366.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A6G9KJC3; -.
DR   SMR; A0A6G9KJC3; -.
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   3: Inferred from homology;
KW   Methyltransferase; S-adenosyl-L-methionine; Transferase.
FT   CHAIN           1..405
FT                   /note="N-methyltransferase nanE"
FT                   /id="PRO_0000452969"
FT   BINDING         238..239
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250|UniProtKB:O04385"
FT   BINDING         261
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01020"
FT   BINDING         290..291
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250|UniProtKB:O04385"
SQ   SEQUENCE   405 AA;  44974 MW;  B168C0C7B55713F5 CRC64;
     MTIANTPAEL LASSISTLAS RYAEKVQAGE NADTEIASIV SACKDLDALV TPPESWNDRM
     AMSYTISTAI ALLLNWDVFQ ILAAQAKPTS LETLATSCGC SKSLLRCALR EAVAHRMLDE
     LSPETYALNS RSSCLLDENK AAWIHYLTDI GLVTAAYLPK YVKSINGKIP EHSHRIALQM
     AFNVDETFYE FLHRKDPKRG VNFDKAMQRH IKGDAQASIE SVFDFSILRP GAVVVDVGGG
     KGHHCIRIAK KHPHLSFIIQ DYEANGPSDG EDTLPEALAR RVRWQRHNFH HKQPMDGADV
     YLLSNILMDN TVSDCNRILT NIVDAMVPNH SVLLVDDAID TLSEDSHSAY SSSMNLHMLS
     CFGTLFRTQE DWLMLFSEVA GGKLSIVSSW MIDAGRMIFA LRRKF