LOLP2_EPIUN
ID LOLP2_EPIUN Reviewed; 184 AA.
AC Q4G3R0;
DT 23-MAY-2018, integrated into UniProtKB/Swiss-Prot.
DT 30-AUG-2005, sequence version 1.
DT 25-MAY-2022, entry version 45.
DE RecName: Full=Inactive cytochrome P450 monooxygenase lolP2 {ECO:0000303|PubMed:15654104};
DE AltName: Full=Loline biosynthesis cluster 2 protein P {ECO:0000303|PubMed:15654104};
GN Name=lolP2 {ECO:0000303|PubMed:15654104};
GN Synonyms=lolP {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: Cytochrome P450 monooxygenase; 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 -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
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 cytochrome P450 family. {ECO:0000305}.
CC -!- CAUTION: Lacks the heme-binding site and is thus probably inactive
CC (PubMed:15654104). {ECO:0000305|PubMed:15654104}.
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DR EMBL; AY723750; AAZ06938.1; -; Genomic_DNA.
DR AlphaFoldDB; Q4G3R0; -.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:InterPro.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR GO; GO:0009820; P:alkaloid metabolic process; IEA:UniProtKB-KW.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR036396; Cyt_P450_sf.
DR SUPFAM; SSF48264; SSF48264; 1.
PE 2: Evidence at transcript level;
KW Alkaloid metabolism; Membrane; Transmembrane; Transmembrane helix.
FT CHAIN 1..184
FT /note="Inactive cytochrome P450 monooxygenase lolP2"
FT /id="PRO_0000444364"
FT TRANSMEM 10..30
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 161..184
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 184 AA; 20669 MW; B41009BB93F3A414 CRC64;
MDLTQFNTAG IVWLTVAAIA ISYILQSSFL SWYRLRHIPG PFLASISSLW NVLNIVTGRT
SPVLEKLPGR YGPLVRTGPN YVLTDDAEIL RHVNGVRSTY PRNGWYEGFR VDEYDHMGSH
IDTSVHDAIK SKVIGGYNGK DGIDLEGAIG SQVKTLVSEI RRTRGSRPRS RPRWMPARWS
RSSP
