CHAPTER 11: Lactate Racemase and Its Niacin-Derived, Covalently-Tethered, Nickel Cofactor

The biological racemization of d- and l-lactic acid was first reported in 1936 and has remained mysterious for eight decades. Recently, considerable advances have been achieved by studying the lactate racemase system in Lactobacillus plantarum. In this species, two operons encompassing a total of nine genes are responsible for this activity, with four genes being strictly required. LarA was shown to be the lactate racemase harboring a nickel ion coordinated by a niacin-derived (SCS) pincer complex. A likely mechanistic hypothesis is that the pincer complex reversibly captures a hydride from lactate, forming the achiral pyruvate intermediate. The three accessory proteins required for lactate racemization catalyze carboxylation, sulfur insertion, and nickel incorporation steps during the synthesis of the lactate racemase cofactor from nicotinic acid adenine dinucleotide. LarE, when expressed in the presence of the other two other accessory proteins LarB and LarC, is able to activate the LarA apoprotein in vitro. This suggests the mature cofactor is assembled on LarE before its transfer to the LarA apoprotein. The presence of the lactate racemase accessory proteins in many genomes lacking larA suggests a wider use of the cofactor in the prokaryotic world.