Lactate racemase is a nickel-dependent enzyme activated by a widespread maturation system.
Racemases catalyse the inversion of stereochemistry in biological molecules, giving the organism the ability to use both isomers. Among them, lactate racemase remains unexplored due to its intrinsic instability and lack of molecular characterization. Here we determine the genetic basis of lactate racemization in Lactobacillus plantarum. We show that, unexpectedly, the racemase is a nickel-dependent enzyme with a novel α/β fold. In addition, we decipher the process leading to an active enzyme, which involves the activation of the apo-enzyme by a single nickel-containing maturation protein that requires preactivation by two other accessory proteins. Genomic investigations reveal the wide distribution of the lactate racemase system among prokaryotes, showing the high significance of both lactate enantiomers in carbon metabolism. The even broader distribution of the nickel-based maturation system suggests a function beyond activation of the lactate racemase and possibly linked with other undiscovered nickel-dependent enzymes.
Institute of Life Sciences, Université catholique de Louvain, Place Croix du Sud 5, 1348 Louvain-La-Neuve, Belgium.
Benoît
B
Desguin
Institute of Life Sciences, Université catholique de Louvain, Place Croix du Sud 5, 1348 Louvain-La-Neuve, Belgium.
Philippe
P
Goffin
Institute of Life Sciences, Université catholique de Louvain, Place Croix du Sud 5, 1348 Louvain-La-Neuve, Belgium.
Eric
E
Viaene
1] NIZO Food Research, PO Box 20, 6710 BA Ede, The Netherlands [2] Host Microbe Interactomics Group, Wageningen University, De Elst 1, 6708 WD, Wageningen, The Netherlands.
Michiel
M
Kleerebezem
Department of Chemistry, University of Massachusetts, 710 North Pleasant Street, Amherst, Massachusetts 01003, USA.
Vlad
V
Martin-Diaconescu
Department of Chemistry, University of Massachusetts, 710 North Pleasant Street, Amherst, Massachusetts 01003, USA.
Michael J
MJ
Maroney
1] Institute of Life Sciences, Université catholique de Louvain, Place Croix du Sud 5, 1348 Louvain-La-Neuve, Belgium [2] Institute of Condensed Matter and Nanosciences, Université catholique de Louvain, Place Louis Pasteur 1, 1348 Louvain-La-Neuve, Belgium.
Jean-Paul
JP
Declercq
1] Institute of Life Sciences, Université catholique de Louvain, Place Croix du Sud 5, 1348 Louvain-La-Neuve, Belgium [2] Institute of Condensed Matter and Nanosciences, Université catholique de Louvain, Place Louis Pasteur 1, 1348 Louvain-La-Neuve, Belgium [3].
Patrice
P
Soumillion
1] Institute of Life Sciences, Université catholique de Louvain, Place Croix du Sud 5, 1348 Louvain-La-Neuve, Belgium [2].
Pascal
P
Hols
D019344:Lactic Acid / Q000378:metabolism*; D048191:Lactiplantibacillus plantarum / Q000201:enzymology* / Q000235:genetics; D009532:Nickel; D017510:Protein Folding; D019998:Racemases and Epimerases / Q000235:genetics / Q000378:metabolism*; D013237:Stereoisomerism
D019344:Lactic Acid; D009532:Nickel; D019998:Racemases and Epimerases; C021498:lactate racemase