LOLD2_EPIUN
ID LOLD2_EPIUN Reviewed; 415 AA.
AC Q5MNH7;
DT 23-MAY-2018, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-2005, sequence version 1.
DT 03-AUG-2022, entry version 53.
DE RecName: Full=Amino acid decarboxylase lolD2 {ECO:0000303|PubMed:18655839};
DE EC=4.1.1.- {ECO:0000305|PubMed:18655839};
DE AltName: Full=Loline biosynthesis cluster 2 protein D {ECO:0000303|PubMed:15654104};
GN Name=lolD2 {ECO:0000303|PubMed:15654104};
GN Synonyms=lolD {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: Amino acid decarboxylase; part of the gene cluster that
CC mediates the biosynthesis of loline alkaloids, potent insecticidal
CC agents composed of a pyrrolizidine ring system and an uncommon ether
CC bridge linking carbons 2 and 7 (PubMed:15654104). Lolines are
CC structurally differentiated by the various modifications of the L-amino
CC group and include norloline, loline, N-methylloline, N-acetylloline, N-
CC acetylnorloline, and N-formylloline (PubMed:15861432, PubMed:25531527).
CC The first committed step is the condensation of O-acetyl-L-homoserine
CC (derived from L-aspartic acid) and L-proline, probably catalyzed by the
CC gamma-type pyridoxal 5'-phosphate(PLP)-dependent enzyme lolC, to give
CC the diamino diacid, NACPP (PubMed:15861432, PubMed:16755627). Ensuing
CC cyclization, 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|UniProtKB:P00860};
CC -!- PATHWAY: Alkaloid biosynthesis. {ECO:0000305|PubMed:15654104}.
CC -!- SUBUNIT: Homodimer (By similarity). {ECO:0000250|UniProtKB:P00860}.
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 Orn/Lys/Arg decarboxylase class-II family.
CC {ECO:0000305}.
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DR EMBL; AY723750; AAV68696.1; -; Genomic_DNA.
DR AlphaFoldDB; Q5MNH7; -.
DR SMR; Q5MNH7; -.
DR GO; GO:0016831; F:carboxy-lyase activity; IEA:UniProtKB-KW.
DR GO; GO:0009820; P:alkaloid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006596; P:polyamine biosynthetic process; IEA:InterPro.
DR Gene3D; 2.40.37.10; -; 1.
DR Gene3D; 3.20.20.10; -; 1.
DR InterPro; IPR009006; Ala_racemase/Decarboxylase_C.
DR InterPro; IPR022643; De-COase2_C.
DR InterPro; IPR022644; De-COase2_N.
DR InterPro; IPR000183; Orn/DAP/Arg_de-COase.
DR InterPro; IPR002433; Orn_de-COase.
DR InterPro; IPR029066; PLP-binding_barrel.
DR PANTHER; PTHR11482; PTHR11482; 1.
DR Pfam; PF02784; Orn_Arg_deC_N; 1.
DR Pfam; PF00278; Orn_DAP_Arg_deC; 1.
DR PRINTS; PR01179; ODADCRBXLASE.
DR PRINTS; PR01182; ORNDCRBXLASE.
DR SUPFAM; SSF50621; SSF50621; 1.
DR SUPFAM; SSF51419; SSF51419; 1.
PE 2: Evidence at transcript level;
KW Alkaloid metabolism; Decarboxylase; Lyase; Pyridoxal phosphate;
KW S-nitrosylation.
FT CHAIN 1..415
FT /note="Amino acid decarboxylase lolD2"
FT /id="PRO_0000444348"
FT ACT_SITE 351
FT /note="Proton donor; shared with dimeric partner"
FT /evidence="ECO:0000250|UniProtKB:P00860"
FT BINDING 194
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P11926"
FT BINDING 231
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P00860"
FT BINDING 266..269
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P00860"
FT BINDING 315..316
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P07805"
FT BINDING 352
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250|UniProtKB:P07805"
FT BINDING 381
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P00860"
FT SITE 190
FT /note="Stacks against the aromatic ring of pyridoxal
FT phosphate and stabilizes reaction intermediates"
FT /evidence="ECO:0000250|UniProtKB:P00860"
FT MOD_RES 62
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000250|UniProtKB:P00860"
FT MOD_RES 351
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000250|UniProtKB:P11926"
SQ SEQUENCE 415 AA; 45607 MW; 129B8FA8FF5F3135 CRC64;
MTTVVREAFE NHVKLVESRN SPGHVLASSE ASFFVADLND VVRKWAAWKE ALPDVTPFFA
VKSSYDRRLI QTLATCGAGF DCASTEEIEL ILSLGIGAER IIFTHPCKPV SSLGLCRKLG
ITLITFDNEC ELRKLHHHYP EAQTVLRVFA DDPTNADPLG TKFGAARDDF DGLVRLVKEL
NMQLAGASFH AAPSVAVDAA AYVRGIRDTA EVFARARQVG LNPTVLDIGG GYTDSTFQQI
AGAVRPAIAE CFKSEVGEGR LRILAEPGTL FSCSPFYLAV KVVARRVNAT AFGHEPATRL
YINDGIYSNF MMRFIVNMTF SPAAVIREGV WHDQADHTMR GEACSLWGRS CDSNDCINRD
CRLGPEVRVG DWLVFKDMGA YTTVCNTTFN GFTSSNHTIY LEPGTHPSRR SPVDL
