Enzymatic Synthesis of Trimethyl-ϵ-caprolactone: Process Intensification and Demonstration on a 100 L Scale: Process Intensification and Demonstration on a 100 L Scale

Jordi Solé, Jan Brummund, Gloria Caminal, Gregorio Álvaro, Martin Schürmann, Marina Guillén

Research output: Contribution to journalArticleResearch

7 Citations (Scopus)

Abstract

© 2019 American Chemical Society. 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%).
Original languageEnglish
Pages (from-to)2336-2344
Number of pages9
JournalOrganic Process Research and Development
Volume23
Issue number11
DOIs
Publication statusPublished - 15 Nov 2019

Keywords

  • BAEYER-VILLIGER MONOOXYGENASES
  • BIOCATALYSIS
  • Baeyer-Villiger monooxygenase (BVMO)
  • DEHYDROGENASE
  • NADPH
  • OXIDATION
  • REGENERATION
  • applied biocatalysis
  • biocatalyst yield
  • branched lactone synthesis
  • preindustrial scale
  • space time yield

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