Metabolism of Formaldehyde in M. extorquens AM1

Abstract

M. extorquens AMI is one of the best studied methylotrophs, a representative of a large group of pink-pigmented facultative methylotrophic bacteria utilizing the serine cycle for formaldehyde assimilation. Reactions of the serine cycle were essentially solved using this organism in J.R. Quayle’s laboratory in the 1960’s and are as follows (Fig. 1). Formaldehyde in the form of methylene tetrahydrofolate (THF) is condensed with glycine by serine hydroxymethyltransferase (SHMT) to produce serine. Serine is transaminated with glyoxylate to produce hydroxypyruvate in the serine glyoxylate aminotransferase (SGAT) reaction. Hydroxypyruvate is reduced to D-glycerate by hydroxypyruvate reductase (HPR), the latter is phosphorylated by glycerate kinase (GK) to produce phosphoglycerate. Phosphoglycerate is converted into PEP by enolase, PEP is carboxylated to oxaloacetate by PEP carboxylase (PEPC), the latter is converted to malate, which is transformed to malyl-CoA by malate thiokinase (MTK) and cleaved to acetyl-CoA and glyoxylate by malyl-CoA lyase (MCL). Glyoxylate is then used to regenerate glycine. In serine methylotrophs possessing isocitrate lyase (ICL), the second molecule of glycine is regenerated from acetyl-CoA in the glyoxylate cycle. In the ICL-minus serine methylotrophs like M. extorquens AM1, the glyoxylate cycle is not operational, and the pathway leading to regeneration of glyoxylate from acetyl-CoA remains unknown.