UniprotKB/SwissProt ID: Q5MNH7 (Q5MNH7)
Gene Name:
lolD2
Organism: Epichloe uncinata (Endophyte fungus)
Function: Amino acid decarboxylase; part of the gene cluster that mediates the biosynthesis of loline alkaloids, potent insecticidal agents composed of a pyrrolizidine ring system and an uncommon ether bridge linking carbons 2 and 7 (PubMed:15654104). Lolines are structurally differentiated by the various modifications of the L-amino group and include norloline, loline, N-methylloline, N-acetylloline, N-acetylnorloline, and N-formylloline (PubMed:15861432, PubMed:25531527). The first committed step is the condensation of O-acetyl-L-homoserine (derived from L-aspartic acid) and L-proline, probably catalyzed by the gamma-type pyridoxal 5'-phosphate(PLP)-dependent enzyme lolC, to give the diamino diacid, NACPP (PubMed:15861432, PubMed:16755627). Ensuing cyclization, decarboxylation, and acetylation steps yield 1-exo-acetamidopyrrolizidine (AcAP) (PubMed:24374065). LolO is required for installation of the ether bridge upon the pathway intermediate, 1-exo-acetamidopyrrolizidine (AcAP) (PubMed:29537853). In sequential 2-oxoglutarate- and O(2)-consuming steps, lolO removes hydrogens from C2 and C7 of AcAP to form both carbon-oxygen bonds in N-acetylnorloline (NANL), the precursor to all other lolines (PubMed:24374065, PubMed:29537853). The enzymes lolD, lolE, lolF and lolT have also been proposed to be involved in the ether-bridge installation (PubMed:15654104). Further processing of the exocyclic moiety of NANL by fungal N-acetamidase (LolN), methyltransferase (LolM), and cytochrome P450 (LolP) enzymes, with occasional involvement of a plant acetyltransferase, generates the other known lolines (PubMed:18655839, PubMed:25531527). LolN transforms NANL to norlonine which is monomethylated and dimethylated to respectively lonine and N-methyllonine (NML) by lolM (PubMed:25531527). LolP catalyzes hydroxylation of the methyl group in N-methylloline (NML) and further oxygenation to N-formylloline (NFL) (PubMed:18655839). A plant acetyltransferase is responsible for the acetylation of loline to form N-acetylloline (NAL) (PubMed:25531527). LolA might interact with aspartate kinase to prevent feedback inhibition of its activity by these end products and thereby promote production of L-homoserine from L-aspartate (PubMed:15654104)
Other Modifications: View all modification sites in dbPTM
Protein Subcellular Localization:
|
|
|
