The isomerisation of glucose to fructose is a critical step towards manufacturing petroleum-free chemicals from lignocellulosic biomass. Here we show that Hf-containing zeolites are unique catalysts for this reaction, enabling true thermodynamic equilibrium to be achieved in a single step during intensified continuous operation, which no chemical or biological catalyst has yet been able to achieve. Unprecedented single pass yields of 58 % are observed at a fructose selectivity of 94 %, and continuous operation for over 100 hours is demonstrated. The unexpected performance of the catalyst is realised following a period of activation within the reactor, during which time interaction with the solvent generates a state of activity that is absent in the synthesised catalyst. Mechanistic studies by X-ray Absorption Spectroscopy, chemisorption FTIR, operando UV-Vis and 1 H- 13 C HSQC NMR indicate that activity arises from isolated Hf(IV) atoms with monofunctional acidic properties.