LTMM_EPIFF
ID LTMM_EPIFF Reviewed; 472 AA.
AC Q56RZ2;
DT 23-MAY-2018, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2005, sequence version 1.
DT 03-AUG-2022, entry version 42.
DE RecName: Full=FAD-dependent monooxygenase ltmM {ECO:0000303|PubMed:15991026};
DE EC=1.-.-.- {ECO:0000305|PubMed:15991026};
DE AltName: Full=Lolitrem B biosynthesis cluster 1 protein M {ECO:0000303|PubMed:15991026};
GN Name=ltmM;
OS Epichloe festucae (strain Fl1).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Clavicipitaceae; Epichloe.
OX NCBI_TaxID=877507;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Fl1;
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 [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=E894;
RA Young C.A., Schardl C.L.;
RT "Epichloe festucae IDT gene cluster.";
RL Submitted (AUG-2011) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION.
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 [4]
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 [5]
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: FAD-dependent monooxygenase; part of the gene cluster 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). The geranylgeranyl diphosphate (GGPP) synthase
CC ltmG is proposed to catalyze the first step in lolitrem biosynthesis
CC (PubMed:16765617, PubMed:15991026). LtmG catalyzes a series of
CC iterative condensations of isopentenyl diphosphate (IPP) with
CC dimethylallyl diphosphate (DMAPP), geranyl diphosphate (GPP), and
CC farnesyl diphosphate (FPP), to form GGPP (PubMed:16765617,
CC PubMed:15991026). GGPP then condenses with indole-3-glycerol phosphate
CC to form 3-geranylgeranylindole, an acyclic intermediate, to be
CC incorporated into paxilline (PubMed:16765617). Either ltmG or ltmC
CC could be responsible for this step, as both are putative prenyl
CC transferases (PubMed:16765617). The FAD-dependent monooxygenase ltmM
CC then catalyzes the epoxidation of the two terminal alkenes of the
CC geranylgeranyl moiety, which is subsequently cyclized by ltmC, to
CC paspaline (PubMed:16765617, PubMed:15991026). The cytochrome P450
CC 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=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000305};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000305|PubMed:15991026}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-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 -!- SIMILARITY: Belongs to the paxM FAD-dependent monooxygenase family.
CC {ECO:0000305}.
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DR EMBL; AY742905; AAW88515.1; -; Genomic_DNA.
DR EMBL; JN613320; AFO85413.1; -; Genomic_DNA.
DR AlphaFoldDB; Q56RZ2; -.
DR SMR; Q56RZ2; -.
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 2: Evidence at transcript level;
KW FAD; Flavoprotein; Glycoprotein; Membrane; Monooxygenase; Oxidoreductase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..472
FT /note="FAD-dependent monooxygenase ltmM"
FT /id="PRO_0000444351"
FT TRANSMEM 7..27
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 450..470
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 306
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 316..320
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT CARBOHYD 186
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 472 AA; 52503 MW; 72251046C254CE08 CRC64;
MTSDFKVIIV GGSVAGLSLA HCLEKIGVSF VVLEKGNQIA PQLGASIGIL PNGGRILDQL
GIFHSIEDEI EPLESAMMRY PDGFSFKSQY PQALHTSFGY PVAFLERQRF LQILYDKLKS
KDCVFTNKRV VSIASGQDKV TAKTSDGAKY LADIVIGADG VHSIVRSEIW RHLKENSQIS
VLEAPNASIK HDYSCIYGIS LNVPQIILGI QLNCLDDGVS IHLFTGKQSK LFWFVIIKTP
QASFAKVEID NTHTARCICE GLRTKKVSDT LCFEDVWSRC TIFKMTPLEE GVFKHWNYGR
LACIGDAIRK MAPNNGQGAN MAIEDACSLA NILQKKISHG SIRDQDINSM FQEFSMAQRA
RTESVCAQSE FLVRMHANQG IGRRLLGRYL IPFLYDAPAG LSGFSISGAT RIEFIDLPTR
SLRGAWGKSW RGSWEFILQS LVYLRPKFRI VYALYLVAAA AFILYCLSSL FP
