LOLT1_EPIUN
ID LOLT1_EPIUN Reviewed; 454 AA.
AC Q5MNI0;
DT 23-MAY-2018, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-2005, sequence version 1.
DT 25-MAY-2022, entry version 50.
DE RecName: Full=L-cysteine desulfhydrase-like protein lolT1 {ECO:0000303|PubMed:15654104};
DE EC=4.4.1.- {ECO:0000305|PubMed:15654104};
DE AltName: Full=Loline biosynthesis cluster 1 protein T {ECO:0000303|PubMed:15654104};
GN Name=lolT1 {ECO:0000303|PubMed:15654104};
GN Synonyms=lolT {ECO:0000303|PubMed:15654104};
OS Epichloe uncinata (Endophyte fungus) (Neotyphodium uncinatum).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Clavicipitaceae; Epichloe.
OX NCBI_TaxID=5050;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], INDUCTION, AND FUNCTION.
RC STRAIN=CBS 102646;
RX PubMed=15654104; DOI=10.1534/genetics.104.035972;
RA Spiering M.J., Moon C.D., Wilkinson H.H., Schardl C.L.;
RT "Gene clusters for insecticidal loline alkaloids in the grass-endophytic
RT fungus Neotyphodium uncinatum.";
RL Genetics 169:1403-1414(2005).
RN [2]
RP FUNCTION.
RX PubMed=15861432; DOI=10.1002/cbic.200400327;
RA Blankenship J.D., Houseknecht J.B., Pal S., Bush L.P., Grossman R.B.,
RA Schardl C.L.;
RT "Biosynthetic precursors of fungal pyrrolizidines, the loline alkaloids.";
RL ChemBioChem 6:1016-1022(2005).
RN [3]
RP FUNCTION.
RX PubMed=16755627; DOI=10.1002/cbic.200600066;
RA Faulkner J.R., Hussaini S.R., Blankenship J.D., Pal S., Branan B.M.,
RA Grossman R.B., Schardl C.L.;
RT "On the sequence of bond formation in loline alkaloid biosynthesis.";
RL ChemBioChem 7:1078-1088(2006).
RN [4]
RP FUNCTION.
RC STRAIN=CBS 102646;
RX PubMed=18655839; DOI=10.1016/j.fgb.2008.07.001;
RA Spiering M.J., Faulkner J.R., Zhang D.X., Machado C., Grossman R.B.,
RA Schardl C.L.;
RT "Role of the LolP cytochrome P450 monooxygenase in loline alkaloid
RT biosynthesis.";
RL Fungal Genet. Biol. 45:1307-1314(2008).
RN [5]
RP FUNCTION.
RX PubMed=24374065; DOI=10.1016/j.phytochem.2013.11.015;
RA Pan J., Bhardwaj M., Faulkner J.R., Nagabhyru P., Charlton N.D.,
RA Higashi R.M., Miller A.F., Young C.A., Grossman R.B., Schardl C.L.;
RT "Ether bridge formation in loline alkaloid biosynthesis.";
RL Phytochemistry 98:60-68(2014).
RN [6]
RP FUNCTION, AND BIOTECHNOLOGY.
RX PubMed=25531527; DOI=10.1371/journal.pone.0115590;
RA Pan J., Bhardwaj M., Nagabhyru P., Grossman R.B., Schardl C.L.;
RT "Enzymes from fungal and plant origin required for chemical diversification
RT of insecticidal loline alkaloids in grass-Epichloe symbiota.";
RL PLoS ONE 9:E115590-E115590(2014).
RN [7]
RP FUNCTION.
RX PubMed=29537853; DOI=10.1021/acs.biochem.8b00157;
RA Pan J., Bhardwaj M., Zhang B., Chang W.C., Schardl C.L., Krebs C.,
RA Grossman R.B., Bollinger J.M. Jr.;
RT "Installation of the ether bridge of lolines by the iron- and 2-
RT oxoglutarate-dependent oxygenase, lolO: regio- and stereochemistry of
RT sequential hydroxylation and oxacyclization reactions.";
RL Biochemistry 57:2074-2083(2018).
CC -!- FUNCTION: L-cysteine desulfhydrase-like protein; part of the gene
CC cluster that mediates the biosynthesis of loline alkaloids, potent
CC insecticidal agents composed of a pyrrolizidine ring system and an
CC uncommon ether bridge linking carbons 2 and 7 (PubMed:15654104).
CC Lolines are structurally differentiated by the various modifications of
CC the L-amino group and include norloline, loline, N-methylloline, N-
CC acetylloline, N-acetylnorloline, and N-formylloline (PubMed:15861432,
CC PubMed:25531527). The first committed step is the condensation of O-
CC acetyl-L-homoserine (derived from L-aspartic acid) and L-proline,
CC probably catalyzed by the gamma-type pyridoxal 5'-phosphate(PLP)-
CC dependent enzyme lolC, to give the diamino diacid, NACPP
CC (PubMed:15861432, PubMed:16755627). Ensuing cyclization,
CC decarboxylation, and acetylation steps yield 1-exo-
CC acetamidopyrrolizidine (AcAP)(PubMed:24374065). LolO is required for
CC installation of the ether bridge upon the pathway intermediate, 1-exo-
CC acetamidopyrrolizidine (AcAP) (PubMed:29537853). In sequential 2-
CC oxoglutarate- and O(2)-consuming steps, lolO removes hydrogens from C2
CC and C7 of AcAP to form both carbon-oxygen bonds in N-acetylnorloline
CC (NANL), the precursor to all other lolines (PubMed:24374065,
CC PubMed:29537853). The enzymes lolD, lolE, lolF and lolT have also been
CC proposed to be involved in the ether-bridge installation
CC (PubMed:15654104). Further processing of the exocyclic moiety of NANL
CC by fungal N-acetamidase (LolN), methyltransferase (LolM), and
CC cytochrome P450 (LolP) enzymes, with occasional involvement of a plant
CC acetyltransferase, generates the other known lolines (PubMed:25531527,
CC PubMed:18655839). LolN transforms NANL to norlonine which is
CC monomethylated and dimethylated to respectively lonine and N-
CC methyllonine (NML) by lolM (PubMed:25531527). LolP catalyzes
CC hydroxylation of the methyl group in N-methylloline (NML) and further
CC oxygenation to N-formylloline (NFL) (PubMed:18655839). A plant
CC acetyltransferase is responsible for the acetylation of loline to form
CC N-acetylloline (NAL) (PubMed:25531527). LolA might interact with
CC aspartate kinase to prevent feedback inhibition of its activity by
CC these end products and thereby promote production of L-homoserine from
CC L-aspartate (PubMed:15654104). {ECO:0000269|PubMed:15654104,
CC ECO:0000269|PubMed:15861432, ECO:0000269|PubMed:16755627,
CC ECO:0000269|PubMed:18655839, ECO:0000269|PubMed:24374065,
CC ECO:0000269|PubMed:25531527, ECO:0000269|PubMed:29537853}.
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000250};
CC -!- PATHWAY: Alkaloid biosynthesis. {ECO:0000269|PubMed:15654104}.
CC -!- INDUCTION: Expression is induced in loline alkaloid-producing cultures
CC as well as in planta (PubMed:15654104). {ECO:0000269|PubMed:15654104}.
CC -!- BIOTECHNOLOGY: Loline alkaloids show broad-spectrum anti-insect
CC activity, and different lolines may have different biological
CC activities (PubMed:25531527). In vitro tests of NFL, NAL, NML, and
CC semisynthetic loline derivatives with long carbon-chain acylations on
CC the 1-amine have shown that many are effective against both fall
CC armyworm larvae and European corn borer larvae, but the effects seem to
CC differ depending on the modifications (PubMed:25531527). N-Formylloline
CC reduces the weight gain of fall armyworms by deterring feeding, and
CC does not significantly affect corn borers (PubMed:25531527). In
CC contrast, NAL reduces the weight gain of corn borer larvae without
CC changing larval feeding behavior, indicating that its effect is due to
CC metabolic toxicity. N-formylloline, NAL, and NML are almost as potent
CC as nicotine in insecticidal activity against green bugs
CC (PubMed:25531527). {ECO:0000305|PubMed:25531527}.
CC -!- SIMILARITY: Belongs to the class-V pyridoxal-phosphate-dependent
CC aminotransferase family. {ECO:0000305}.
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DR EMBL; AY723749; AAV68709.1; -; Genomic_DNA.
DR AlphaFoldDB; Q5MNI0; -.
DR SMR; Q5MNI0; -.
DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR GO; GO:0009820; P:alkaloid metabolic process; IEA:UniProtKB-KW.
DR Gene3D; 3.40.640.10; -; 1.
DR Gene3D; 3.90.1150.10; -; 1.
DR InterPro; IPR000192; Aminotrans_V_dom.
DR InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major.
DR InterPro; IPR015422; PyrdxlP-dep_Trfase_small.
DR Pfam; PF00266; Aminotran_5; 1.
DR SUPFAM; SSF53383; SSF53383; 1.
PE 2: Evidence at transcript level;
KW Alkaloid metabolism; Lyase; Pyridoxal phosphate.
FT CHAIN 1..454
FT /note="L-cysteine desulfhydrase-like protein lolT1"
FT /id="PRO_0000444365"
FT MOD_RES 227
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000250"
SQ SEQUENCE 454 AA; 50486 MW; 41DD8D1042D5CDB8 CRC64;
MTVNSKRIPF GKPMLEAFCM DPEYTNLNSS SCGSWPKVVS KQIRDYWSLL EAQPDLFSEF
SQGLVLQEAR IGLAHLVHAA VSECVLVSNV TTGIFTVLYN QAFEERDVVV TLSTTYGAID
HGITSLAETR PFKTRRVEFE LPTTGQKIVS QFETAMAQIR ADGLRPRLAI LETIVSIPAV
RMPFEDLLRV CQKEGIMTLV DGAHSVGQFE VNLQELQPDF FVSDCHKWLF VPRPCAVLYV
AERNQHMMRS VIPTSFGFIP KNGNSRLPLW SQMVSASETA SSFETLFAYT ATSDYMPHLC
IPAALRFRRD VCGGEAAIYE YIKWLAKEGG DKIADILQTE VLEEPGLGAG VDGQMRNCGI
VTVRLPLAIA TGPSTAPAHV PGGALTEKEV GPAVRYLTKA LAERYKTWIP IIDYRGWIWA
RLCAQVYLEV SDFEMAGNSL KVICEEILNR EMGQ
