IDTM_CLAPA
ID IDTM_CLAPA Reviewed; 491 AA.
AC J7FK10;
DT 02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2012, sequence version 1.
DT 03-AUG-2022, entry version 22.
DE RecName: Full=FAD-dependent monooxygenase idtM {ECO:0000303|PubMed:23468653};
DE EC=1.-.-.- {ECO:0000305|PubMed:29457197};
DE AltName: Full=Indole-diterpene biosynthesis cluster protein M {ECO:0000303|PubMed:23468653};
GN Name=idtM {ECO:0000303|PubMed:23468653};
OS Claviceps paspali (Rye ergot fungus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Clavicipitaceae; Claviceps.
OX NCBI_TaxID=40601;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], IDENTIFICATION, AND FUNCTION.
RC STRAIN=RRC-1481;
RX PubMed=23468653; DOI=10.1371/journal.pgen.1003323;
RA Schardl C.L., Young C.A., Hesse U., Amyotte S.G., Andreeva K., Calie P.J.,
RA Fleetwood D.J., Haws D.C., Moore N., Oeser B., Panaccione D.G.,
RA Schweri K.K., Voisey C.R., Farman M.L., Jaromczyk J.W., Roe B.A.,
RA O'Sullivan D.M., Scott B., Tudzynski P., An Z., Arnaoudova E.G.,
RA Bullock C.T., Charlton N.D., Chen L., Cox M., Dinkins R.D., Florea S.,
RA Glenn A.E., Gordon A., Gueldener U., Harris D.R., Hollin W., Jaromczyk J.,
RA Johnson R.D., Khan A.K., Leistner E., Leuchtmann A., Li C., Liu J., Liu J.,
RA Liu M., Mace W., Machado C., Nagabhyru P., Pan J., Schmid J., Sugawara K.,
RA Steiner U., Takach J.E., Tanaka E., Webb J.S., Wilson E.V., Wiseman J.L.,
RA Yoshida R., Zeng Z.;
RT "Plant-symbiotic fungi as chemical engineers: Multi-genome analysis of the
RT Clavicipitaceae reveals dynamics of alkaloid loci.";
RL PLoS Genet. 9:E1003323-E1003323(2013).
RN [2]
RP FUNCTION, AND PATHWAY.
RX PubMed=29457197; DOI=10.1007/s00253-018-8807-x;
RA Kozak L., Szilagyi Z., Vago B., Kakuk A., Toth L., Molnar I., Pocsi I.;
RT "Inactivation of the indole-diterpene biosynthetic gene cluster of
RT Claviceps paspali by Agrobacterium-mediated gene replacement.";
RL Appl. Microbiol. Biotechnol. 102:3255-3266(2018).
RN [3]
RP FUNCTION.
RX PubMed=32077051; DOI=10.1007/s12223-020-00777-6;
RA Kozak L., Szilagyi Z., Toth L., Pocsi I., Molnar I.;
RT "Functional characterization of the idtF and idtP genes in the Claviceps
RT paspali indole diterpene biosynthetic gene cluster.";
RL Folia Microbiol. (Praha) 65:605-613(2020).
CC -!- FUNCTION: FAD-dependent monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of paspalitrems, indole-diterpene (IDT)
CC mycotoxins that are potent tremorgens in mammals (PubMed:23468653,
CC PubMed:29457197, PubMed:32077051). The geranylgeranyl diphosphate
CC (GGPP) synthase idtG is proposed to catalyze the first step in IDT
CC biosynthesis via catalysis of a series of iterative condensations of
CC isopentenyl diphosphate (IPP) with dimethylallyl diphosphate (DMAPP),
CC geranyl diphosphate (GPP), and farnesyl diphosphate (FPP), to form GGPP
CC (Probable). Condensation of indole-3-glycerol phosphate with GGPP by
CC the prenyltransferase idtC then forms 3-geranylgeranylindole (3-GGI)
CC (Probable). Epoxidation of the two terminal alkenes of the
CC geranylgeranyl moiety by the FAD-dependent monooxygenase idtM, and
CC cyclization by the terpene cyclase idtB then leads to the production of
CC paspaline (Probable). The cytochrome P450 monooxygenase idtP then
CC catalyzes oxidative elimination of the pendant methyl group at C-12 of
CC paspaline and generates the C-10 ketone to yield 13-desoxypaxilline
CC (PubMed:32077051). The cytochrome P450 monooxygenase idtQ may catalyze
CC the C-13 oxidation of 13-desoxypaxilline to afford paxilline
CC (Probable). Considering that both paspalicine and paxilline were
CC detected in C.paspali, idtQ also catalyzes the formation of paspalinine
CC from 13-desoxypaxilline via paspalicine as an intermediate (Probable).
CC Finally, the alpha-prenyltransferase idtF prenylates paspalinine at the
CC C-20 or the C-21 positions to yield paspalitrems A and C, respectively
CC (PubMed:32077051). The hydroxylation of paspalitrem A at C-32 by a
CC still unknown oxidase affords paspalitrem B (Probable).
CC {ECO:0000269|PubMed:23468653, ECO:0000269|PubMed:29457197,
CC ECO:0000269|PubMed:32077051, ECO:0000305|PubMed:29457197}.
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000305};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000305|PubMed:23468653}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-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; JN613322; AFO85424.1; -; Genomic_DNA.
DR AlphaFoldDB; J7FK10; -.
DR SMR; J7FK10; -.
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; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 3: Inferred from homology;
KW FAD; Flavoprotein; Membrane; Monooxygenase; Oxidoreductase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..491
FT /note="FAD-dependent monooxygenase idtM"
FT /id="PRO_0000451436"
FT TRANSMEM 448..468
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 130
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 307
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 317..321
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
SQ SEQUENCE 491 AA; 53888 MW; E88D3F97F5BFEA20 CRC64;
MADDFKVVIV GGSVAGLSLA HCLERLGVSY VVLEKGSQIA PQLGASIGIL PNGGRILDQL
GIFRDVEDEI EPLNFAVIRY ADGFSFRSQY PKALHSSYGY PVSFLERQKF IQILYDKLRG
KNHVHTRKRV VSIVDGPGKA LIRTDDGDEY DADMVVGADG VHSVVRSEIW RHAKEAAGTA
VTEEEPNADI KYDYACVYGI SVNVPHADTG VQLSSLSDGV SIHLFAGKGS KFFWFIMVRT
SRDEFLELKK DSAHMARRTC EGLGSKRLSD AVYFRDVWSR CTVYQMTPLE EGVFRQWNRG
RLVCIGDAIR KMAPNIGQGA NMAIEDAAQL SNLIREMLAS PRKASATTVE KMLRDFAAMQ
KARTKSMCGQ SEFLVRMHAN EGFGRRLLGR YLIPSLQDAP AGLAGLSIRG AVKLECAGVP
SRTLGKAWEG SWGSSLRNLM YLRPRLGILS LVYVVAGLAM MYMSIYLVVP ARLAAQAFDV
SRDGTEGKGG G
