One-pot chemoenzymatic synthesis of glycolic acid from formaldehyde

Abstract

Glycolic acid is an important building block of biodegradable polymers. Herein, we report an efficient selective and atom-economical approach for the synthesis of glycolic acid based on a catalytic C–C coupling reaction of the inexpensive C1 compound formaldehyde followed by selective oxidation. The developed approach relies on an evolved formolase with improved activity at a high formaldehyde concentration (up to 1 M) and controlled oxidation by the oxidant, sodium chlorite or H₂O₂. Kinetic characterization, molecular dynamics simulation and binding free energy calculation demonstrated that the identified amino acid substitutions of the evolved formolase stabilize the first reaction intermediate state TPP-FA (thiamine pyrophosphate-formaldehyde) and the second intermediate state TPP-GA (thiamine pyrophosphate-glycolaldehyde), which is beneficial for the C–C coupling product generation, especially C2 GA at a high concentration of formaldehyde. The chemoenzymatic approach established in this work provides a new opportunity to manufacture monomers of biodegradable polymers from CO₂ derivatives.