LTMC_EPIFI
ID LTMC_EPIFI Reviewed; 345 AA.
AC Q15FB2;
DT 23-MAY-2018, integrated into UniProtKB/Swiss-Prot.
DT 25-JUL-2006, sequence version 1.
DT 03-AUG-2022, entry version 49.
DE RecName: Full=Prenyltransferase ltmC {ECO:0000303|PubMed:16765617};
DE EC=2.5.1.- {ECO:0000305};
DE AltName: Full=Lolitrem B biosynthesis cluster 2 protein C {ECO:0000303|PubMed:16765617};
GN Name=ltmC {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.
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: Prenyltransferase; part of the gene cluster that mediates the
CC biosynthesis of lolitrems, indole-diterpene mycotoxins that are potent
CC tremorgens in mammals, and are synthesized by clavicipitaceous fungal
CC endophytes in association with their grass hosts (PubMed:16765617). The
CC geranylgeranyl diphosphate (GGPP) synthase ltmG is proposed to catalyze
CC the first step in lolitrem biosynthesis (PubMed:16765617,
CC PubMed:15991026). LtmG catalyzes 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 (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=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q12051};
CC Note=Binds 3 Mg(2+) ions per subunit. {ECO:0000250|UniProtKB:Q12051};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000305|PubMed:16765617}.
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 -!- SIMILARITY: Belongs to the FPP/GGPP synthase family. {ECO:0000305}.
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DR EMBL; DQ443465; ABF20225.1; -; Genomic_DNA.
DR AlphaFoldDB; Q15FB2; -.
DR SMR; Q15FB2; -.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0008299; P:isoprenoid biosynthetic process; IEA:InterPro.
DR Gene3D; 1.10.600.10; -; 1.
DR InterPro; IPR008949; Isoprenoid_synthase_dom_sf.
DR InterPro; IPR000092; Polyprenyl_synt.
DR Pfam; PF00348; polyprenyl_synt; 1.
DR SUPFAM; SSF48576; SSF48576; 1.
PE 2: Evidence at transcript level;
KW Glycoprotein; Magnesium; Metal-binding; Transferase.
FT CHAIN 1..345
FT /note="Prenyltransferase ltmC"
FT /id="PRO_0000444324"
FT BINDING 112
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 119
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 119
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 123
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 123
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 128
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 212
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 213
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 243
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 250
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 260
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT CARBOHYD 130
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 345 AA; 38997 MW; 708DE5A6C4FA50BD CRC64;
MTSGAWLVAR PAAIEIAALL FAFTLGYLVK YTINYQSVVS QAIDHYGYGY ERTSHEGIGG
SNGKIPDCPY SYVISLYGHN HFSPLVDFLH PTLKHKYPKK HSLILDIMDA VHLCLIMVDD
ICDHSPKRKN HTTAHLLYGS CETANRAYFV LTKVINRAMK EQPVLGIELL RALELILEGQ
DMSLVWRRDG LRSFESYGEE SLLTYKNMAL LKTGTLFVLL GRLLNQGGHQ SDDLLGRFGW
YAQLQNDCKN IYSEEYAFNK GTVAEDLRNR ELSFPVVVAL NDKHTEPQIR KAFQSQNQGD
IKRALQALES PSVKNTCLKT LQEAGQGLEN LVAVWGRKEQ MHFTK
