LTME_EPIFI
ID LTME_EPIFI Reviewed; 788 AA.
AC Q15FB7;
DT 23-MAY-2018, integrated into UniProtKB/Swiss-Prot.
DT 25-JUL-2006, sequence version 1.
DT 03-AUG-2022, entry version 62.
DE RecName: Full=Multi-functional prenyltransferase ltmE {ECO:0000303|PubMed:16765617};
DE EC=2.5.1.- {ECO:0000305|PubMed:16765617};
DE AltName: Full=Lolitrem B biosynthesis cluster 3 protein E {ECO:0000303|PubMed:16765617};
GN Name=ltmE {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: Multi-functional prenyltransferase; part of the gene cluster
CC that mediates the biosynthesis of lolitrems, indole-diterpene
CC mycotoxins that are potent tremorgens in mammals, and are synthesized
CC by 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=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:0000269|PubMed:22750140}.
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: Does not produce lolitremanes but accumulates
CC both simple and O-prenylated paspalanes (PubMed:22750140).
CC {ECO:0000269|PubMed:22750140}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the FPP/GGPP synthase
CC family. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the tryptophan
CC dimethylallyltransferase family. {ECO:0000305}.
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DR EMBL; DQ443465; ABF20220.1; -; Genomic_DNA.
DR AlphaFoldDB; Q15FB7; -.
DR SMR; Q15FB7; -.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004659; F:prenyltransferase activity; IEA:UniProt.
DR GO; GO:0009820; P:alkaloid metabolic process; IEA:InterPro.
DR GO; GO:0008299; P:isoprenoid biosynthetic process; IEA:InterPro.
DR CDD; cd13929; PT-DMATS_CymD; 1.
DR Gene3D; 1.10.600.10; -; 1.
DR InterPro; IPR033964; Aro_prenylTrfase.
DR InterPro; IPR017795; Aro_prenylTrfase_DMATS.
DR InterPro; IPR008949; Isoprenoid_synthase_dom_sf.
DR InterPro; IPR000092; Polyprenyl_synt.
DR PANTHER; PTHR40627; PTHR40627; 1.
DR Pfam; PF00348; polyprenyl_synt; 1.
DR Pfam; PF11991; Trp_DMAT; 1.
DR SFLD; SFLDS00036; Aromatic_Prenyltransferase; 1.
DR SUPFAM; SSF48576; SSF48576; 1.
DR TIGRFAMs; TIGR03429; arom_pren_DMATS; 1.
PE 2: Evidence at transcript level;
KW Magnesium; Metal-binding; Transferase.
FT CHAIN 1..788
FT /note="Multi-functional prenyltransferase ltmE"
FT /id="PRO_0000444325"
FT REGION 283..337
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 283..311
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 314..337
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 18
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 51
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 58
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 58
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 67
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 151
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 152
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 182
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 189
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 199
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 404..405
FT /ligand="L-tryptophan"
FT /ligand_id="ChEBI:CHEBI:57912"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT BINDING 427
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT BINDING 599
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT BINDING 601
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT BINDING 603
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT BINDING 687
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
SQ SEQUENCE 788 AA; 87565 MW; AC01B3CFD4DFA7B5 CRC64;
MKPTTRCPFD YLVSQCGKHH FKTFVQLLSP LLQDEDPDRY ALILDIMDAV HFSAILIDDI
ANQSALRRNQ PAAHVVFGET ETATRAYLVL LRVVNRTMRE NPVLAGELLN SLEEIHQGQD
ESLVWRRDGL ETFPVADDER LAAYVRMSRL KTGSLFVLLG RLLANGGTEF DDLLVRFGLY
AQLQHDCKNI YSPEYALNKG SVAEDLRNGE LSYPVVVALI ENKAEGIVGE ALRTRSDGDT
EQALRVLESP AVKDACLHAL EAASVGLEDL VEAWGRREKM RSDTLDGDDL TRPSTITQHE
QDDHVDRAAI DAKSDASGSS NKSLTPPETA PTTDTLSETA VGDISSVDVD YWTRRCVPII
GSLLKSCRVY SEAERETQLR FLQEHVLPNL GPRPSSPGSQ IQSMATFSGF PLQPSINLSG
SGQAKVRYTF EPLDSLSGTE VDPFALAPAQ RVLEKLSTLL GVWPGWIDAL IAAYHPTREE
VEQLHPNLHE YLRGVLVRTT GRQDVQVPPM PRMWVCFVAL DLEGASQALK VYFDPKIKEA
VTGIPSCKYT CQILRTVDRF GNAKAVDMLE QFLAEEHSIG AVELIAIDCV PEEMQPSARI
KVYVHTMSNS FQTVRKYMTM GGRCMDPATL EGLENLHDVW YSLLGESQGI VNEEYSKPLT
GFSSMQHHLY FSYEMTPGNA DPGVKVYIPV QSYAPDDKTI AQNYEANFRQ LNWPWGEPGV
YEAVIESALG PVKHSRATFL HGGSSFIFSK GRGVYQSIYL DPPLEEGGNI AVFEHHDDQD
TIVDLGNM
