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Kinetic insights into ϵ‐caprolactone synthesis: Improvement of an enzymatic cascade reaction
Author(s) -
Scherkus Christian,
Schmidt Sandy,
Bornscheuer Uwe T.,
Gröger Harald,
Kara Selin,
Liese Andreas
Publication year - 2017
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.26258
Subject(s) - lipase , cyclohexanol , cyclohexanone , chemistry , alcohol dehydrogenase , hydrolysis , substrate (aquarium) , yield (engineering) , product inhibition , combinatorial chemistry , monooxygenase , cascade , thioglycolic acid , microreactor , alcohol , enzyme , organic chemistry , catalysis , chromatography , materials science , non competitive inhibition , biology , cytochrome p450 , metallurgy , ecology
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.