Enzymatic Synthesis of Trimethyl-ϵ-caprolactone : Process Intensification and Demonstration on a 100 L Scale
Solé Ferré, Jordi (Universitat Autònoma de Barcelona. Departament d'Enginyeria Química, Biològica i Ambiental)
Brummund, Jan (InnoSyn B.V.)
Caminal i Saperas, Glòria (Institut de Química Avançada de Catalunya)
Álvaro, Gregorio (Universitat Autònoma de Barcelona. Departament d'Enginyeria Química, Biològica i Ambiental)
Schürmann, Martin (InnoSyn B.V.)
Guillén, Marina (Universitat Autònoma de Barcelona. Departament d'Enginyeria Química, Biològica i Ambiental)

Data:	2019
Resum:	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%).
Ajuts:	European Commission 635734 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-1462
Drets:	Tots els drets reservats.
Llengua:	Anglès
Document:	Article ; recerca ; Versió acceptada per publicar
Matèria:	Baeyer−Villiger monooxygenase (BVMO) ; Branched lactone synthesis ; Preindustrial scale ; Applied biocatalysis ; Biocatalyst yield ; Space time yield
Publicat a:	Organic process research and development, Vol. 23, Issue 11 (November 2019) , p. 2336-2344, ISSN 1520-586X

DOI: 10.1021/acs.oprd.9b00185

Postprint 29 p, 1.1 MB

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