NODM_HYPPI
ID NODM_HYPPI Reviewed; 463 AA.
AC A0A2I6PIZ2;
DT 10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT 28-MAR-2018, sequence version 1.
DT 03-AUG-2022, entry version 12.
DE RecName: Full=FAD-dependent monooxygenase nodM {ECO:0000303|PubMed:29283570};
DE EC=1.-.-.- {ECO:0000305|PubMed:29283570};
DE AltName: Full=Nodulisporic acid biosynthesis cluster protein M {ECO:0000303|PubMed:29283570};
GN Name=nodM {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-dependent 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=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:A6T923};
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 paxM FAD-dependent monooxygenase family.
CC {ECO:0000305}.
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DR EMBL; MG182145; AUM60051.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A2I6PIZ2; -.
DR SMR; A0A2I6PIZ2; -.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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; 2.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 3: Inferred from homology;
KW FAD; Flavoprotein; Membrane; Monooxygenase; Oxidoreductase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..463
FT /note="FAD-dependent monooxygenase nodM"
FT /id="PRO_0000446562"
FT TRANSMEM 5..25
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 438..458
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 35..36
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 131
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 231..233
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 305
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 315..319
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
SQ SEQUENCE 463 AA; 51861 MW; B93368C3ABBC3E4D CRC64;
MSTPEFKVII VGGSLAGLTL AHCLLRAGIS HIVLERRSVI APEEGASIGI LPNGARVLDQ
LGIYEHIQDT TEPLSTAHIR YPDGFYFSSR YPEIIKERFG YPIAFLPRRR LLEILYTSYP
DHSNIYTNKN VIKVQSHDNQ VSVLTEDGNT YRGDLVVGAD GVNSRVLSEI WKLAGNPSLT
KREGRGRTIE YACVFGISSP ISDLKPGEQV NAFYDGLTIV TIHGRNGEIF WFFIKKLSRR
YIYPDLIRLQ QKDAEGICEE AKSLTVWKGV TFGDIWERRE TASLTVLDEF LHHTWSWDRS
VCVGDSIHKM TPNFGQGANT AIEDSAALAN LLHSLIKEKR AEKPTDSDIS LLLRQFKSQR
LRRVQKIYKM SRFVTRLQAR DGLLNTLLGR HYAPYAADLP AKIASGCIAG AEVLDYLPLP
KVTGAGWNRG HRRSTMYILL GFTGVFTSAL AMVVLLHIRD IAS
