LTMS_EPIFF
ID LTMS_EPIFF Reviewed; 283 AA.
AC J7FJH0;
DT 23-MAY-2018, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2012, sequence version 1.
DT 25-MAY-2022, entry version 8.
DE RecName: Full=Lolitrem B biosynthesis cluster protein S {ECO:0000303|PubMed:23468653};
DE Flags: Precursor;
GN Name=ltmS {ECO:0000303|PubMed:23468653};
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], IDENTIFICATION, AND FUNCTION.
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.
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 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: Part of the gene cluster that mediates the biosynthesis of
CC lolitrems, indole-diterpene mycotoxins that are potent tremorgens in
CC mammals, and are synthesized by clavicipitaceous fungal endophytes in
CC association with their grass hosts (PubMed:23468653). 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, ECO:0000269|PubMed:23468653}.
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 ltmS family. {ECO:0000305}.
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DR EMBL; JN613320; AFO85412.1; -; Genomic_DNA.
DR AlphaFoldDB; J7FJH0; -.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
PE 2: Evidence at transcript level;
KW Membrane; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..283
FT /note="Lolitrem B biosynthesis cluster protein S"
FT /id="PRO_5003792126"
FT TRANSMEM 73..93
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 112..132
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 157..177
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 219..239
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 250..270
FT /note="Helical"
FT /evidence="ECO:0000255"
SQ SEQUENCE 283 AA; 31666 MW; 014DE8E3AA4CE7A3 CRC64;
MSRSDWIFIS LQGFFCLAGV IWKSREGYPI IDFPCPLQFI DSSDATLSYG TTSPWFGFRA
VASMQSIWDN GPWFWLHLML YIAQLVGLIL IILHETVPHG AFLRKFESLA ALGYLSYTVG
LSTAFPVFSL WILNQYRAEK LVTAWPRRQE KAFLRTIFWC TGISHIGIFM VAIVATLLHR
DATAPFHIGN SLLGVPDCSQ FPCSEIAARH ARLRQINEMT GTSSGFFLTV GLFSQALEAE
NKHLSLRVMV RMFFVSLIAG PAAGSADVLL LRDSITRSKK DCG
