Properties of 2-C-Methyl-D-Erythritol 2,4-Cyclopyrophosphate, an Intermediate in Nonmevalonate Isoprenoid Biosynthesis

Abstract

Extraction and purification from the biomass of Corynebacterium ammoniagenes of 2-C-methyl-D-erythritol 2,4-cyclopyrophosphate (MEC) was associated with its spontaneous transformation into a number of derivatives (which was due to the pyrophosphate bond lability and the formation of complexes with metals). These derivatives included 1,2-cyclophospho-4-phosphate, 2,4-diphosphate, 2,3-cyclophosphate, 1,4-diphosphate, and 3,5-diphosphate (identified by ¹H, ³¹P, and ¹³C NMR spectroscopy) and accounted for about 10% of the MEC. When added to a solution of DNA in the presence of the Fenton reagent, MEC prevented DNA decomposition. In addition, MEC slowed down the interaction of the reagent with tempol radicals, which indicates that complexation of ferrous ions by MEC attenuates their ability to catalyze the formation of hydroxyl radicals from hydrogen peroxide. In the presence of 0.23 mM MEC, the rate of respiration of rat liver mitochondria increased by 1.8 times. At 0.1–1.0 mM, MEC activated in vitro proliferation of human Vgamma9 T cells. It is suggested that MEC acts as an endogenous stabilizing agent for bacterial cells subjected to oxidative stress and as an immunomodulator for eukaryotic hosts.