ID   NODO_HYPPI              Reviewed;         448 AA.
AC   A0A2I6PJ02;
DT   10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT   28-MAR-2018, sequence version 1.
DT   25-MAY-2022, entry version 11.
DE   RecName: Full=FAD-linked oxidoreductase nodO {ECO:0000303|PubMed:29283570};
DE            EC=1.1.1.- {ECO:0000305|PubMed:29283570};
DE   AltName: Full=Nodulisporic acid biosynthesis cluster protein O {ECO:0000303|PubMed:29283570};
GN   Name=nodO {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: FAD-linked oxidoreductase; 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=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000305};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000305|PubMed:29283570}.
CC   -!- SIMILARITY: Belongs to the oxygen-dependent FAD-linked oxidoreductase
CC       family. {ECO:0000305}.
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DR   EMBL; MG182145; AUM60052.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A2I6PJ02; -.
DR   SMR; A0A2I6PJ02; -.
DR   GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR   Gene3D; 3.30.465.10; -; 1.
DR   InterPro; IPR016166; FAD-bd_PCMH.
DR   InterPro; IPR036318; FAD-bd_PCMH-like_sf.
DR   InterPro; IPR016169; FAD-bd_PCMH_sub2.
DR   InterPro; IPR006094; Oxid_FAD_bind_N.
DR   Pfam; PF01565; FAD_binding_4; 1.
DR   SUPFAM; SSF56176; SSF56176; 1.
DR   PROSITE; PS51387; FAD_PCMH; 1.
PE   3: Inferred from homology;
KW   FAD; Flavoprotein; Oxidoreductase.
FT   CHAIN           1..448
FT                   /note="FAD-linked oxidoreductase nodO"
FT                   /id="PRO_0000446567"
FT   DOMAIN          35..206
FT                   /note="FAD-binding PCMH-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
SQ   SEQUENCE   448 AA;  50159 MW;  CB9228CFD71FEE9D CRC64;
     MEVSSSETLP ILWRTSPPSN DYENARCRVF NGRQPEHFPL AIVKANKVEH IVAAVKLAAE
     LDACIAVRSG GHSLSCWTIR HGAILIDLED YQHLSYDDEI HEVQASPSTL GADLLTFLAK
     KKRFFPVGHS GDIGLGGYLL QGGIGLNSRG YGYACEYITG LDIITADGEI KHCDKTENSD
     LYWAARGAGP EFPAIVIRFF LKTCPLLPVC KRSRYVWPAA MYGKVFKWLE ELLNSLSEDV
     EIAVFGFVLP RLNQPGLVLH ATAFGDSSEN VREKLTPIIK NHPPGTFLAE DFVSTNFPED
     YDLGKDTMPR GARYFTDSVF LKPGIDFVAT CKGMFTELKH PRALAYWQPM KTNIDRILPD
     MAMSIHSHHY VSLLAIYEDP SEDQQQISWI IDRMKSLEPA ILGTFIGDAH PVERPSNYWS
     EEAEERVITI GRKWDPSSRI RGIVLSDA