An Enzyme Cascade Synthesis of ε-Caprolactone and its Oligomers

Poly‐ε‐caprolactone (PCL) is chemically produced on an industrial scale in spite of the need for hazardous peracetic acid as an oxidation reagent. Although Baeyer–Villiger monooxygenases (BVMO) in principle enable the enzymatic synthesis of ε‐caprolactone (ε‐CL) directly from cyclohexanone with molecular oxygen, current systems suffer from low productivity and are subject to substrate and product inhibition. The major limitations for such a biocatalytic route to produce this bulk chemical were overcome by combining an alcohol dehydrogenase with a BVMO to enable the efficient oxidation of cyclohexanol to ε‐CL. Key to success was a subsequent direct ring‐opening oligomerization of in situ formed ε‐CL in the aqueous phase by using lipase A from Candida antarctica, thus efficiently solving the product inhibition problem and leading to the formation of oligo‐ε‐CL at more than 20 g L−1 when starting from 200 mM cyclohexanol. This oligomer is easily chemically polymerized to PCL. Let's polymerize! Oligo‐ε‐caprolactone was produced in a one‐pot enzymatic cascade synthesis starting from cyclohexanol. In the first step, cyclohexanol is oxidized by an alcohol dehydrogenase (ADH) in combination with the cyclohexanone monooxygenase (CHMO) from Acinetobacter calcoaceticus, followed by direct ring‐opening oligomerization of ε‐caprolactone in an exclusively aqueous phase by lipase A from Candida antarctica (CAL‐A).