LTMQ_EPIFI
ID LTMQ_EPIFI Reviewed; 537 AA.
AC Q15FB4;
DT 23-MAY-2018, integrated into UniProtKB/Swiss-Prot.
DT 25-JUL-2006, sequence version 1.
DT 03-AUG-2022, entry version 53.
DE RecName: Full=Cytochrome P450 monooxygenase ltmQ {ECO:0000303|PubMed:16765617};
DE EC=1.-.-.- {ECO:0000305|PubMed:16765617};
DE AltName: Full=Lolitrem B biosynthesis cluster 2 protein Q {ECO:0000303|PubMed:16765617};
GN Name=ltmQ {ECO:0000303|PubMed:16765617};
OS Epichloe festucae var. lolii (Neotyphodium lolii) (Acremonium lolii).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Clavicipitaceae; Epichloe.
OX NCBI_TaxID=73839;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Lp19;
RX PubMed=16765617; DOI=10.1016/j.fgb.2006.04.004;
RA Young C.A., Felitti S., Shields K., Spangenberg G., Johnson R.D.,
RA Bryan G.T., Saikia S., Scott B.;
RT "A complex gene cluster for indole-diterpene biosynthesis in the grass
RT endophyte Neotyphodium lolii.";
RL Fungal Genet. Biol. 43:679-693(2006).
RN [2]
RP FUNCTION.
RC STRAIN=Lp19;
RX PubMed=15991026; DOI=10.1007/s00438-005-1130-0;
RA Young C.A., Bryant M.K., Christensen M.J., Tapper B.A., Bryan G.T.,
RA Scott B.;
RT "Molecular cloning and genetic analysis of a symbiosis-expressed gene
RT cluster for lolitrem biosynthesis from a mutualistic endophyte of perennial
RT ryegrass.";
RL Mol. Genet. Genomics 274:13-29(2005).
RN [3]
RP INDUCTION.
RX PubMed=20519633; DOI=10.1104/pp.110.158451;
RA Eaton C.J., Cox M.P., Ambrose B., Becker M., Hesse U., Schardl C.L.,
RA Scott B.;
RT "Disruption of signaling in a fungal-grass symbiosis leads to
RT pathogenesis.";
RL Plant Physiol. 153:1780-1794(2010).
RN [4]
RP FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=22750140; DOI=10.1016/j.febslet.2012.06.035;
RA Saikia S., Takemoto D., Tapper B.A., Lane G.A., Fraser K., Scott B.;
RT "Functional analysis of an indole-diterpene gene cluster for lolitrem B
RT biosynthesis in the grass endosymbiont Epichloe festucae.";
RL FEBS Lett. 586:2563-2569(2012).
CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene clusters that
CC mediates the biosynthesis of lolitrems, indole-diterpene mycotoxins
CC that are potent tremorgens in mammals, and are synthesized by
CC clavicipitaceous fungal endophytes in association with their grass
CC hosts (PubMed:16765617, PubMed:22750140). The geranylgeranyl
CC diphosphate (GGPP) synthase ltmG is proposed to catalyze the first step
CC in lolitrem biosynthesis (PubMed:16765617, PubMed:15991026). LtmG
CC catalyzes a series of iterative condensations of isopentenyl
CC diphosphate (IPP) with dimethylallyl diphosphate (DMAPP), geranyl
CC diphosphate (GPP), and farnesyl diphosphate (FPP), to form GGPP
CC (PubMed:16765617, PubMed:15991026). GGPP then condenses with indole-3-
CC glycerol phosphate to form 3-geranylgeranylindole, an acyclic
CC intermediate, to be incorporated into paxilline (PubMed:16765617).
CC Either ltmG or ltmC could be responsible for this step, as both are
CC putative prenyl transferases (PubMed:16765617). The FAD-dependent
CC monooxygenase ltmM then catalyzes the epoxidation of the two terminal
CC alkenes of the geranylgeranyl moiety, which is subsequently cyclized by
CC ltmB, to paspaline (PubMed:16765617, PubMed:15991026). The cytochrome
CC P450 monooxygenases ltmQ and ltmP can sequentially oxidize paspaline to
CC terpendole E and terpendole F (PubMed:22750140). Alternatively, ltmP
CC converts paspaline to an intermediate which is oxidized by ltmQ to
CC terpendole F (PubMed:22750140). LtmF, ltmK, ltmE and ltmJ appear to be
CC unique to the epichloe endophytes (PubMed:16765617, PubMed:15991026).
CC The prenyltransferase ltmF is involved in the 27-hydroxyl-O-prenylation
CC (PubMed:22750140). The cytochrome P450 monooxygenase ltmK is required
CC for the oxidative acetal ring formation (PubMed:22750140). The multi-
CC functional prenyltransferase ltmE is required for C20- and C21-
CC prenylations of the indole ring of paspalanes and acts together with
CC the cytochrome P450 monooxygenase ltmJ to yield lolitremanes by
CC multiple oxidations and ring closures (PubMed:22750140). The
CC stereoisomer pairs of lolitriol and lolitrem N or lolitrem B and
CC lolitrem F may be attributed to variations in the way in which ring
CC closure can occur under the action of ltmJ (PubMed:22750140). While the
CC major product of this pathway is lolitrem B, the prenyl transferases
CC and cytochrome P450 monooxygenases identified in this pathway have a
CC remarkable versatility in their regio- and stereo-specificities to
CC generate a diverse range of metabolites that are products of a
CC metabolic grid rather than a linear pathway (PubMed:22750140).
CC {ECO:0000269|PubMed:15991026, ECO:0000269|PubMed:16765617,
CC ECO:0000269|PubMed:22750140}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:22750140}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- INDUCTION: Expression is down-regulated when the stress-activated
CC mitogen-activated protein kinase (sakA) is deleted (PubMed:20519633).
CC {ECO:0000269|PubMed:20519633}.
CC -!- DISRUPTION PHENOTYPE: Accumulates the paspalane 13-desoxypaxilline
CC (PubMed:22750140). {ECO:0000269|PubMed:22750140}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; DQ443465; ABF20223.1; -; Genomic_DNA.
DR AlphaFoldDB; Q15FB4; -.
DR SMR; Q15FB4; -.
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; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 2: Evidence at transcript level;
KW Glycoprotein; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW Oxidoreductase; Transmembrane; Transmembrane helix.
FT CHAIN 1..537
FT /note="Cytochrome P450 monooxygenase ltmQ"
FT /id="PRO_0000444334"
FT TRANSMEM 10..30
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 476
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"
FT CARBOHYD 182
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 188
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 310
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 537 AA; 61484 MW; 2759A4E15BF29105 CRC64;
MKMLTEHFDF PKLNFATIVI SGATIIGIIF LRYLNYPTKV NVPVVGIGVR YTKWLAAIIN
VRHARQSIRE GYAKYGDFAF QIPTMTRMEV FICDRQMTRE YQNVDDYHLS FRAVMTEEFQ
FKWLLPGQAH EARIIPNSVI AKALSWQRTR ANKPSDPFFE SFSAEFMQGF QEEMRRLIQY
QNSSVMSNRS GAVLDPAHGW HAVPCFPLAL KVIGRLTTYV LFGKPLCQDA TFLNMCCQFG
DVIPRDAIIL RSWPALARPL IVKILSAPRV MGKLRNILIV EIKSRRESHE TNPMSDILDF
TMAWVDRHPN ASFDDQHIAE MMINTIFAAL HTSSQLVVHT IFELASRPEY SDALLEEIDA
CFEKHGKGTK AALDSMFKVD SFIKETQRFN PLDASALARL ALKDFTFSNG LNIPKGSVIF
TPNSPIFEDE RYYKDPKVFD GFRFARMRND PKLGLFCDLT ATNEQSMHFG TGRHACPGRF
MVSDEVKLAV IHILSNFDFC IENFGPRPAN QPFGKFLLPD MSAKIWLREK RAREKNL
