L-erythrulose synthesis from glycerol by a multi enzymatic cascade reaction

Glycerol dehydrogenase (GDH) selectively catalyzes the oxidation of glycerol, a low value bio-based platform chemical, to useful dihydroxyacetone (DHA). However, this biocatalytic reaction is hampered by strong enzyme inhibition by the product (DHA) and by the need for an expensive cofactor (NAD+). We propose a biocatalytic cascade to solve these issues. First, an aldolase (Fructose-6-phosphate aldolase: FSAA129S) is used to rapidly consume DHA and funnel the reaction towards another stable, non-inhibiting, and high-value product: L-erythrulose. Second, an optimized cofactor recycling is introduced (based on NADH oxidase coupled with catalase). The four enzymes can be co-immobilized onto a resin to obtain a multifunctional heterogeneous catalyst. L-erythrulose production up to 120 mM is demonstrated, with 100% selectivity.