ID   NANF_ASPNN              Reviewed;         459 AA.
AC   A0A6G9KH61;
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=FAD-dependent monooxygenase nanF {ECO:0000303|PubMed:32182055};
DE            EC=1.1.1.- {ECO:0000269|PubMed:32182055};
DE   AltName: Full=Nanangelenin A biosynthesis cluster protein F {ECO:0000303|PubMed:32182055};
GN   Name=nanF {ECO:0000303|PubMed:32182055}; ORFNames=FE257_013097;
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: FAD-dependent monooxygenase; 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   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000305};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:32182055}.
CC   -!- SIMILARITY: Belongs to the paxM FAD-dependent monooxygenase family.
CC       {ECO:0000305}.
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DR   EMBL; MT024570; QIQ51367.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A6G9KH61; -.
DR   SMR; A0A6G9KH61; -.
DR   GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR   GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR   GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR   Gene3D; 3.50.50.60; -; 1.
DR   InterPro; IPR002938; FAD-bd.
DR   InterPro; IPR036188; FAD/NAD-bd_sf.
DR   Pfam; PF01494; FAD_binding_3; 1.
DR   SUPFAM; SSF51905; SSF51905; 1.
PE   3: Inferred from homology;
KW   FAD; Flavoprotein; Monooxygenase; Oxidoreductase.
FT   CHAIN           1..459
FT                   /note="FAD-dependent monooxygenase nanF"
FT                   /id="PRO_0000452970"
FT   BINDING         327
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:A6T923"
FT   BINDING         337..341
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:A6T923"
SQ   SEQUENCE   459 AA;  49832 MW;  006E388050C3A977 CRC64;
     MTVDDSLSPA GVATPHSSGI RVVVVGLGIA GLTTAIECHR KGHTVIALEK SPVIRVLGDS
     LGLGSNATNV LEKWADGKIL QQLKSLADDI SIFEALDSAG KLYAKDDAKG FGADNGMIIN
     RGSLATTLHE YAKMLEIDIR FGAAVTGHWE DESAAGVIIN GEQRLVADCV IGCDGIHSKT
     REAVLTKEPT AVPSGQAVFR ASFDSTSVCN DPNARWILAE KGVRDRLSQY MAEGGLALSL
     ATGKRGQNIT WQLWHEDNHN ANELWSEHNS AKLENALGMI RHWPIYSKVV PILRHTPKEA
     LTDFKLVNRA ALPTWISHAG RIIIIGDAAH PVLPIVGQGG GQGIEDAATV AICLQLAGKT
     HISLALQAVE RLRYARTSII QSSGPKIYAG VRNPDWKAIE KDPSLIMLPR PKWIFGYDVP
     RDVYEQFPLV KRAIEEGSSY TPKNIPPGGR YEFLHDFKE