ID   NODB_HYPPI              Reviewed;         243 AA.
AC   A0A2I6PJ07;
DT   10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT   28-MAR-2018, sequence version 1.
DT   25-MAY-2022, entry version 8.
DE   RecName: Full=Terpene cyclase nodB {ECO:0000303|PubMed:29283570};
DE            EC=4.2.3.- {ECO:0000305|PubMed:29283570};
DE   AltName: Full=Nodulisporic acid biosynthesis cluster protein B {ECO:0000303|PubMed:29283570};
GN   Name=nodB {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: Terpene cyclase; part of the gene cluster that mediates the
CC       biosynthesis of the indole diterpenes nodulisporic acids (NA).
CC       Nodulisporic acid A (NAA) and its chemically modified derivatives are
CC       of particular significance because of their highly potent insecticidal
CC       activity against blood-feeding arthropods and lack of observable
CC       adverse effects on mammals, in particular the tremogenicity associated
CC       with the paspaline-derived IDTs is not observed (PubMed:29283570). The
CC       geranylgeranyl diphosphate (GGPP) synthase ggs1, localized outside of
CC       the cluster, is proposed to catalyze the first step in nodulisporic
CC       acid biosynthesis via conversion of farnesyl pyrophosphate and
CC       isopentyl pyrophosphate into geranylgeranyl pyrophosphate (GGPP)
CC       (PubMed:29283570). Condensation of indole-3-glycerol phosphate with
CC       GGPP by the prenyl transferase nodC then forms 3-geranylgeranylindole
CC       (3-GGI) (PubMed:29283570). Epoxidation by the FAD-dependent
CC       monooxygenase nodM leads to a single-epoxidized-GGI that is substrate
CC       of the terpene cyclase nodB for cyclization to yield emindole SB
CC       (PubMed:29283570). The terminal methyl carbon, C28, of emindole SB is
CC       then oxidized by the cytochrome P450 monooxygenase nodW to produce
CC       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   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:29283570}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC       protein {ECO:0000255}.
CC   -!- SIMILARITY: Belongs to the paxB family. {ECO:0000305}.
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DR   EMBL; MG182145; AUM60064.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A2I6PJ07; -.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR   InterPro; IPR039020; PaxB-like.
DR   PANTHER; PTHR42038; PTHR42038; 1.
PE   3: Inferred from homology;
KW   Glycoprotein; Lyase; Membrane; Transmembrane; Transmembrane helix.
FT   CHAIN           1..243
FT                   /note="Terpene cyclase nodB"
FT                   /id="PRO_0000446543"
FT   TRANSMEM        19..39
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        50..70
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        75..95
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        112..132
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        134..154
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        169..189
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        205..225
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        111
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ   SEQUENCE   243 AA;  26951 MW;  D76968C613A9C308 CRC64;
     MDGFDRSNAP VEYQRVEWIS DIFVFGMGVC WLINYAGMIY TSLQEQTYSM APLALCCNFA
     WEMVYGLIYP SKSRIEQGVF LAGLVVNLGV MYTAIRFAPN EWAHAPLVMN NITLIFALGV
     LGSLTGHLAL AAEIGPALGY SWGAVACQLL LSVGGFCQLL GRSSSRGASY TLWLSRFIGS
     GCVVGFAILR YMYWSEAFNW LNSPLVLWSL GVFIAVDSLY GICLWNVKKY EHGQERSNAR
     KAQ