NAND_ASPNN
ID NAND_ASPNN Reviewed; 435 AA.
AC A0A6G9KJL7;
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=Prenyltransferase nanD {ECO:0000303|PubMed:32182055};
DE EC=2.5.1.- {ECO:0000269|PubMed:32182055};
DE AltName: Full=Nanangelenin A biosynthesis cluster protein D {ECO:0000303|PubMed:32182055};
GN Name=nanD {ECO:0000303|PubMed:32182055}; ORFNames=FE257_001451;
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: Prenyltransferase; part of the gene cluster that mediates the
CC biosynthesis of the benzazepine alkaloid nanangelenin A which contains
CC an unprecedented 3,4-dihydro-1-benzazepine-2,5-dione-N-prenyl-N-
CC 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 tryptophan dimethylallyltransferase family.
CC {ECO:0000305}.
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DR EMBL; MT024570; QIQ51364.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A6G9KJL7; -.
DR SMR; A0A6G9KJL7; -.
DR GO; GO:0004659; F:prenyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0009820; P:alkaloid metabolic process; IEA:InterPro.
DR GO; GO:0044249; P:cellular biosynthetic process; IEA:UniProt.
DR GO; GO:1901576; P:organic substance biosynthetic process; IEA:UniProt.
DR CDD; cd13929; PT-DMATS_CymD; 1.
DR InterPro; IPR033964; Aro_prenylTrfase.
DR InterPro; IPR017795; Aro_prenylTrfase_DMATS.
DR InterPro; IPR012148; DMATS-type_fun.
DR PANTHER; PTHR40627; PTHR40627; 1.
DR Pfam; PF11991; Trp_DMAT; 1.
DR PIRSF; PIRSF000509; Trp_DMAT; 1.
DR SFLD; SFLDS00036; Aromatic_Prenyltransferase; 1.
DR TIGRFAMs; TIGR03429; arom_pren_DMATS; 1.
PE 1: Evidence at protein level;
KW Prenyltransferase; Transferase.
FT CHAIN 1..435
FT /note="Prenyltransferase nanD"
FT /id="PRO_0000452968"
FT BINDING 101
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 114
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 202
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 204
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 206
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 280
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 282
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 364
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 429
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 433
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
SQ SEQUENCE 435 AA; 49596 MW; D20E050E00CDBA24 CRC64;
MAIIEPQMEN QNTIPIYARE ETPYDTLSKV LTFSNIDQEE YWRRIAPLLG KLLQQGSNYT
IHQQYQHLCF YALHVIPLLG PFPVEGRSSY NCPLGGVGAI EPSQNFQKSG TSLRYTFEPT
STGAISGRSD PFNRFMIDDA LSRFRQAGVR FNPHLYEALK KEVLLTDEEA EAICQHHDVP
KMEFRAQACI AVDLDGGNMS VKLYVYPMLK ATLLNIPNWE LCLNAIRHVD GEGQFTSATA
ALETYLRTQC PTTVREQTSA TTQVSYIACD LVDLQRARFK VYLFDLHVSF ERIITHWTMG
GRLNDEVTMS GLGILRELWD ELKIPEGRRK PIERPPKPGD GPTMPLFFNY EMKAGDRLPK
VKAYLPLVGM PEMPIARKLA AFFQRYGFPV EGRQYVDTLA GYFPDEDLEI VTHHQAFLSF
SYSAKTGPYM TIYYH
