Biocatalytic Production of a Nylon 6 Precursor from Caprolactone in Continuous Flow

6-Aminocaproic acid (6ACA) is a key building block and an attractive precursor of caprolactam, which is used to synthesize nylon 6, one of the most common polymers manufactured nowadays. (Bio)-production of platform chemicals from renewable feedstocks is instrumental to tackle climate change and decrease fossil fuel dependence. Here, the cell-free biosynthesis of 6ACA from 6-hydroxycaproic acid was achieved using a co-immobilized multienzyme system based on horse liver alcohol dehydrogenase, Halomonas elongata transaminase, and Lactobacillus pentosus NADH oxidase for in-situ cofactor recycling, with >90% molar conversion (m.c.) The integration of a step to synthesize hydroxy-acid from lactone by immobilized Candida antarctica lipase B resulted in >80% m.c. of epsilon-caprolactone to 6ACA, >20 % of delta-valerolactone to 5-aminovaleric acid, and 30 % of gamma-butyrolactone to gamma-aminobutyric acid in one-pot batch reactions. Two serial packed-bed reactors were set up using these biocatalysts and applied to the continuous-flow synthesis of 6ACA from epsilon-caprolactone, achieving a space-time yield of up to 3.31 g(6ACA) h(-1) L-1 with a segmented liquid/air flow for constant oxygen supply.