Institute of Biochemistry, Dept. of Biotechnology & Enzyme Catalysis, Greifswald University, Felix-Hausdorff-Strasse 4, 17487 Greifswald (Germany).
Angew Chem Int Ed Engl. 2015 Feb 23;54(9):2784-7. doi: 10.1002/anie.201410633. Epub 2015 Jan 19.
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.
聚己内酯（PCL）尽管需要使用危险的过氧乙酸作为氧化试剂，但仍在工业规模上通过化学方法生产。尽管 Baeyer-Villiger 单加氧酶（BVMO）原则上可以使分子氧直接从环己酮催化合成ε-己内酯（ε-CL），但目前的系统存在生产率低的问题，并且易受到底物和产物抑制。通过将醇脱氢酶与 BVMO 结合，以有效地将环己醇氧化为 ε-CL，克服了这种生物催化途径生产这种大宗化学品的主要限制。成功的关键是使用来自南极假丝酵母的脂肪酶 A 在水相中直接开环聚合原位形成的 ε-CL，从而有效地解决了产物抑制问题，并在以 200mM 环己醇为起始原料时形成了超过 20g/L 的ε-CL 低聚物。这种低聚物很容易通过化学方法聚合形成 PCL。
