Synthetic metabolons for metabolic engineering.

Abstract

It has been proposed that enzymes can associate into complexes (metabolons) that increase the efficiency of metabolic pathways by channelling substrates between enzymes. Metabolons may increase flux by increasing the local concentration of intermediates, decreasing the concentration of enzymes needed to maintain a given flux, directing the products of a pathway to a specific subcellular location or minimizing the escape of reactive intermediates. Metabolons can be formed by relatively loose non-covalent protein-protein interaction, anchorage to membranes, and (in bacteria) by encapsulation of enzymes in protein-coated microcompartments. Evidence that non-coated metabolons are effective at channelling substrates is scarce and difficult to obtain. In plants there is strong evidence that small proportions of glycolytic enzymes are associated with the outside of mitochondria and are effective in substrate channelling. More recently, synthetic metabolons, in which enzymes are scaffolded to synthetic proteins or nucleic acids, have been expressed in microorganisms and these provide evidence that scaffolded enzymes are more effective than free enzymes for metabolic engineering. This provides experimental evidence that metabolons may have a general advantage and opens the way to improving the outcome of metabolic engineering in plants by including synthetic metabolons in the toolbox.