title: Kinetic insights into ϵ-caprolactone synthesis: Improvement of an enzymatic cascade reaction.
abstract: A computational approach for the simulation and prediction of a linear three-step enzymatic cascade for the synthesis of ϵ-caprolactone (ECL) coupling an alcohol dehydrogenase (ADH), a cyclohexanone monooxygenase (CHMO), and a lipase for the subsequent hydrolysis of ECL to 6-hydroxyhexanoic acid (6-HHA). A kinetic model was developed with an accuracy of prediction for a fed-batch mode of 37% for substrate cyclohexanol (CHL), 90% for ECL, and >99% for the final product 6-HHA. Due to a severe inhibition of the CHMO by CHL, a batch synthesis was shown to be less efficient than a fed-batch approach. In the fed-batch synthesis, full conversion of 100 mM CHL was 28% faster with an analytical yield of 98% compared to 49% in case of the batch synthesis. The lipase-catalyzed hydrolysis of ECL to 6-HHA circumvents the inhibition of the CHMO by ECL enabling a 24% higher product concentration of 6-HHA compared to ECL in case of the fed-batch synthesis without lipase. Biotechnol. Bioeng. 2017;114: 1215-1221. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Institute of Technical Biocatalysis, Hamburg University of Technology, Denickestr. 15, Hamburg 21073, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Scherkus
authors.affiliation: Department of Biotechnology, Delft University of Technology, Delft, The Netherlands.|Department of Biotechnology and Enzyme Catalysis, Institute of Biochemistry, Greifswald University, Greifswald, Germany.
authors.forename: Sandy
authors.initials: S
authors.lastname: Schmidt
authors.affiliation: Department of Biotechnology and Enzyme Catalysis, Institute of Biochemistry, Greifswald University, Greifswald, Germany.
authors.forename: Uwe T
authors.initials: UT
authors.lastname: Bornscheuer
authors.affiliation: Organic Chemistry I, Faculty of Chemistry, Bielefeld University, Bielefeld, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Gröger
authors.affiliation: Institute of Technical Biocatalysis, Hamburg University of Technology, Denickestr. 15, Hamburg 21073, Germany.
authors.forename: Selin
authors.initials: S
authors.lastname: Kara
authors.affiliation: Institute of Technical Biocatalysis, Hamburg University of Technology, Denickestr. 15, Hamburg 21073, Germany.
authors.forename: Andreas
authors.identifier: 0000-0002-4867-9935
authors.initials: A
authors.lastname: Liese
mesh_terms: D000426:Alcohol Dehydrogenase / Q000737:chemistry*; D002208:Caproates / Q000138:chemical synthesis*; D004789:Enzyme Activation; D006868:Hydrolysis; D007700:Kinetics; D007783:Lactones / Q000138:chemical synthesis*; D008049:Lipase / Q000737:chemistry*; D009097:Multienzyme Complexes / Q000737:chemistry; D010105:Oxygenases / Q000737:chemistry*; D013011:Sorbic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D013379:Substrate Specificity
chemical_list: D002208:Caproates; D007783:Lactones; D009097:Multienzyme Complexes; C121056:caprolactone; C085223:6-hydroxy-2,4-hexadienoic acid; D000426:Alcohol Dehydrogenase; D010105:Oxygenases; C019961:cyclohexanone oxygenase; D008049:Lipase; D013011:Sorbic Acid
keywords: computer simulation; enzymatic cascades; oxidoreductases; reaction engineering; ϵ-caprolactone