NODW_HYPPI
ID NODW_HYPPI Reviewed; 532 AA.
AC A0A2I6PJ08;
DT 10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT 28-MAR-2018, sequence version 1.
DT 03-AUG-2022, entry version 10.
DE RecName: Full=Cytochrome P450 monooxygenase nodW {ECO:0000303|PubMed:29283570};
DE EC=1.-.-.- {ECO:0000305|PubMed:29283570};
DE AltName: Full=Nodulisporic acid biosynthesis cluster protein W {ECO:0000303|PubMed:29283570};
GN Name=nodW {ECO:0000303|PubMed:29283570};
OS Hypoxylon pulicicidum.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Xylariomycetidae; Xylariales; Hypoxylaceae; Hypoxylon.
OX NCBI_TaxID=1243767;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], IDENTIFICATION, FUNCTION, AND PATHWAY.
RC STRAIN=MF5954 / ATCC 74245;
RX PubMed=29283570; DOI=10.1021/jacs.7b10909;
RA Van de Bittner K.C., Nicholson M.J., Bustamante L.Y., Kessans S.A., Ram A.,
RA van Dolleweerd C.J., Scott B., Parker E.J.;
RT "Heterologous biosynthesis of nodulisporic acid F.";
RL J. Am. Chem. Soc. 140:582-585(2018).
CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of the indole diterpenes nodulisporic acids
CC (NA). Nodulisporic acid A (NAA) and its chemically modified derivatives
CC are of particular significance because of their highly potent
CC insecticidal activity against blood-feeding arthropods and lack of
CC observable adverse effects on mammals, in particular the tremogenicity
CC associated with the paspaline-derived IDTs is not observed
CC (PubMed:29283570). The geranylgeranyl diphosphate (GGPP) synthase ggs1,
CC localized outside of the cluster, is proposed to catalyze the first
CC step in nodulisporic acid biosynthesis via conversion of farnesyl
CC pyrophosphate and isopentyl pyrophosphate into geranylgeranyl
CC pyrophosphate (GGPP) (PubMed:29283570). Condensation of indole-3-
CC glycerol phosphate with GGPP by the prenyl transferase nodC then forms
CC 3-geranylgeranylindole (3-GGI) (PubMed:29283570). Epoxidation by the
CC FAD-dependent monooxygenase nodM leads to a single-epoxidized-GGI that
CC is substrate of the terpene cyclase nodB for cyclization to yield
CC emindole SB (PubMed:29283570). The terminal methyl carbon, C28, of
CC emindole SB is then oxidized by the cytochrome P450 monooxygenase nodW
CC to produce nodulisporic acid F (NAF), the pentacyclic core of NAA
CC (PubMed:29283570). NAF is converted to nodulisporic acid E (NAE) via
CC prenylation. This step is probably performed by one of the indole
CC diterpene prenyltransferases nodD1 or nodD2 (Probable). Several
CC oxidation steps performed by the FAD-linked oxidoreductase nodO and one
CC of the cytochrome P450 monooxygenase nodR, nodX or nodZ further convert
CC NAE to nodulisporic acid D (NAD) (Probable). NAD is substrate of
CC cytochrome P450 monooxygenase nodJ to produce the precursor of
CC nodulisporic acid C (NAC), converted to NAC by one of the indole
CC diterpene prenyltransferases nodD1 or nodD2 (Probable). The FAD-
CC dependent monooxygenase nodY2 then oxidizes NAC to nodulisporic acid B
CC (NAB) (Probable). Finally NAB is converted to NAA by one of the
CC cytochrome P450 monooxygenases nodR, nodX or nodZ (Probable).
CC {ECO:0000269|PubMed:29283570, ECO:0000305|PubMed:29283570}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000305|PubMed:29283570}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; MG182145; AUM60065.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A2I6PJ08; -.
DR SMR; A0A2I6PJ08; -.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR002403; Cyt_P450_E_grp-IV.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00465; EP450IV.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
PE 3: Inferred from homology;
KW Heme; Iron; Membrane; Metal-binding; Monooxygenase; Oxidoreductase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..532
FT /note="Cytochrome P450 monooxygenase nodW"
FT /id="PRO_0000446580"
FT TRANSMEM 2..21
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 31..53
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 60..82
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 469
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P04798"
SQ SEQUENCE 532 AA; 60458 MW; E5CEB7FF21FCC45F CRC64;
MTLAILGISC LAAVLSHTIL FIRGEWDKHA PVLFHCFITC PIALICSLLA VGLYGITFMF
IQVWLCYISS ICLSIIIYRL FLHPLRDFPG KVSARLSTLR WMKTAAVDRK WHLEVQNMHS
VYGDFVRIRP REISVNNFNA IRDLAKCARG PFYDVNYPHK SLQMTRDRNF HLRRKKIWQK
AFSPNAMLAH EGHVRQCCQE LMGYLSSRGG QPVEVTELMQ RVTFESMGWL VFGKAFNMIQ
KGLSHPGFTQ LRSVKQLGGL LLWAPWTLIL LRNLPFLRSK ATSWLQWCSQ EVVERKQNPT
MTHDLFSHLL DDESKDTDDL VYDSELAVVA GSDSTASTLT AILFLLATHP DKQAILQKEV
DDMNIGGLPM PTSTLVNMPY LNSCINEALR LYPAVMSGSQ RETGPGGVIL DGQFIPEHML
VSMPTYTIHR DKRNFVRPDE FIPERWTSQS HLTLNPDAFI PFSVGVYGCL GKPFAMMEMR
MVISSIMSRF NLRLLPGRPM SHEASAPAYD CYIIHIPAFS LVFEPRAGNI WA
