Unfamiliar metabolic links in the central carbon metabolism

Abstract

The central carbon metabolism of all organisms is considered to follow a well established fixed scheme. However, recent studies of autotrophic carbon fixation in prokaryotes revealed unfamiliar metabolic links. A new route interconnects acetyl-coenzyme A (CoA) via 3-hydroxypropionate with succinyl-CoA. Succinyl-CoA in turn may be metabolized via 4-hydroxybutyrate to two molecules of acetyl-CoA; a reversal of this route would result in the assimilation of two molecules of acetyl-CoA into C4 compounds. C5-dicarboxylic acids are a rather neglected class of metabolites; yet, they play a key role not only in one of the CO2 fixation cycles, but also in two acetate assimilation pathways that replace the glyoxylate cycle. C5 compounds such as ethylmalonate, methylsuccinate, methylmalate, mesaconate, itaconate and citramalate or their CoA esters are thereby linked to the acetyl-CoA, propionyl-CoA, glyoxylate and pyruvate pools. A novel carboxylase/reductase converts crotonyl-CoA into ethylmalonyl-CoA; similar reductive carboxylations apply to other alpha-beta-unsaturated carboxy-CoA thioesters. These unfamiliar metabolic links may provide useful tools for metabolic engineering.