Enzymatic Synthesis of Trimethyl-ϵ-caprolactone: Process Intensification and Demonstration on a 100 L Scale
Optimization and scaling up of the Baeyer-Villiger oxidation of 3,3,5-trimethyl-cyclohexanone to trimethyl-ϵ-caprolactones (CHLs) were studied to demonstrate this technology on a 100 L pilot plant scale. The reaction was catalyzed by a cyclohexanone monooxygenase from Thermocrispum municipale that u...
| Autores: | , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión aceptada para publicación |
| Fecha de publicación: | 2019 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/193639 |
| Acceso en línea: | http://hdl.handle.net/10261/193639 |
| Access Level: | acceso abierto |
| Palabra clave: | Applied biocatalysis Preindustrial scale Baeyer-Villiger monooxygenase Space time yield Biocatalyst yield Branched lactone synthesis |
| Sumario: | Optimization and scaling up of the Baeyer-Villiger oxidation of 3,3,5-trimethyl-cyclohexanone to trimethyl-ϵ-caprolactones (CHLs) were studied to demonstrate this technology on a 100 L pilot plant scale. The reaction was catalyzed by a cyclohexanone monooxygenase from Thermocrispum municipale that utilizes the costly redox cofactor nicotinamide adenine dinucleotide phosphate (reduced form), which was regenerated by a glucose dehydrogenase (GDH). As a first stage, different cyclohexanone monooxygenase formulations were tested: cell-free extract, whole cells, fermentation broth, and sonicated fermentation broth. Using broth resulted in the highest yield (63%) and required the least biocatalyst preparation effort. Two commercial glucose dehydrogenases (GDH-105 and GDH-01) were evaluated, resulting in similar performances. Substrate dosing rates and biocatalyst loadings were optimized. On a 30 mL scale, the best conditions were found when 30 mM h-1 dosing rate, 10% (v/v) cyclohexanone monooxygenase broth, and 0.05% (v/v) of glucose dehydrogenase (GDH-01) liquid enzyme formulation were applied. These same conditions (with oxygen instead of air) were applied on a 1 L scale with 92% conversion, achieving a specific activity of 13.3 U gcell wet weight (cww) -1, a space time yield of 3.4 gCHL L-1 h-1, and a biocatalyst yield of 0.83 gCHL gcww -1. A final 100 L demonstration was performed in a pilot plant facility. After 9 h, the reaction reached 85% conversion, 12.8 U gcww -1, a space time yield of 2.7 g L-1 h-1, and a biocatalyst yield of 0.60 gCHL gcww -1. The extraction of product resulted in 2.58 kg of isolated final product. The overall isolated CHL yield was 76% (distal lactone 47% and proximal lactone 53%). © 2019 American Chemical Society. |
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