title: LanCL proteins are not Involved in Lanthionine Synthesis in Mammals.
abstract: LanC-like (LanCL) proteins are mammalian homologs of bacterial LanC enzymes, which catalyze the addition of the thiol of Cys to dehydrated Ser residues during the biosynthesis of lanthipeptides, a class of natural products formed by post-translational modification of precursor peptides. The functions of LanCL proteins are currently unclear. A recent proposal suggested that LanCL1 catalyzes the addition of the Cys of glutathione to protein- or peptide-bound dehydroalanine (Dha) to form lanthionine, analogous to the reaction catalyzed by LanC in bacteria. Lanthionine has been detected in human brain as the downstream metabolite lanthionine ketimine (LK), which has been shown to have neuroprotective effects. In this study, we tested the proposal that LanCL1 is involved in lanthionine biosynthesis by constructing LanCL1 knock-out mice and measuring LK concentrations in their brains using a mass spectrometric detection method developed for this purpose. To investigate whether other LanCL proteins (LanCL2/3) may confer a compensatory effect, triple knock-out (TKO) mice were also generated and tested. Very similar concentrations of LK (0.5-2.5 nmol/g tissue) were found in LanCL1 knock-out, TKO and wild type (WT) mouse brains, suggesting that LanCL proteins are not involved in lanthionine biosynthesis.
authors.affiliation: Department of Chemistry and Howard Hughes Medical Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
authors.forename: Chang
authors.initials: C
authors.lastname: He
authors.affiliation: Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, United States of America.
authors.forename: Min
authors.initials: M
authors.lastname: Zeng
authors.affiliation: Department of Chemistry and Howard Hughes Medical Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
authors.forename: Debapriya
authors.initials: D
authors.lastname: Dutta
authors.affiliation: Department of Chemistry and Howard Hughes Medical Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
authors.forename: Tong Hee
authors.initials: TH
authors.lastname: Koh
authors.affiliation: Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, United States of America.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Chemistry and Howard Hughes Medical Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
authors.forename: Wilfred A
authors.initials: WA
authors.lastname: van der Donk
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D000818:Animals; D001923:Brain Chemistry; D013058:Mass Spectrometry; D008565:Membrane Proteins / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D028044:Phosphate-Binding Proteins; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency / Q000378:metabolism*; D013440:Sulfides
chemical_list: C572254:LANCL2 protein, mouse; C485882:Lancl1 protein, mouse; C000628748:Lancl3 protein, mouse; D008565:Membrane Proteins; D028044:Phosphate-Binding Proteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D013440:Sulfides; C001520:lanthionine; D000409:Alanine