transaldolases

Transaldolases are enzymes that catalyze the transfer of a three-carbon dihydroxyacetone unit in the non-oxidative phase of the pentose phosphate pathway (PPP). By reshuffling carbon skeletons, they help balance ribose-5-phosphate, required for nucleotide synthesis, with glycolytic intermediates.

In the canonical reaction, sedoheptulose-7-phosphate and glyceraldehyde-3-phosphate are converted to erythrose-4-phosphate and fructose-6-phosphate. This transaldolase step works alongside transketolase to interconvert sugars of different lengths, enabling flexible routing of carbon through the PPP according to cellular needs.

Transaldolases are categorized into two mechanistic classes. Class I transaldolases form a Schiff base with an active-site lysine, creating a covalent enzyme–substrate intermediate. Class II transaldolases are metal-dependent and do not rely on a Schiff base; they use a distinct catalytic strategy. These classes are distributed across bacteria, archaea, and eukaryotes, reflecting evolutionary diversification.

Genetic and structural notes vary by organism. In bacteria such as Escherichia coli, multiple tal genes (for example talA and talB) encode transaldolase activities. In humans, the major cytosolic transaldolase is encoded by TALDO1. Many transaldolases function as dimers or higher-order oligomers and require specific active-site residues or metal cofactors for activity.

Physiological relevance and applications: transaldolase activity helps maintain PPP flux, contributing to cellular NADPH production and biosynthetic precursor supply. Deficiencies in transaldolase can cause rare metabolic disorders. Beyond physiology, modulating transaldolase activity is explored in metabolic engineering to optimize PPP flux for biotechnological production.