Toward Upscaled Biocatalytic Preparation of Lactone Building Blocks for Polymer Applications

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Although Baeyer–Villiger monooxygenases (BVMOs) have gained attention in recent years, there are few cases of their upscaled application for lactone synthesis. A thermostable cyclohexanone monooxygenase from Thermocrispum municipale (TmCHMO) was applied to the oxidation of 3,3,5-trimethylcyclohexanone using a glucose dehydrogenase (GDH) for cofactor regeneration. The reaction progress was improved by optimizing the biocatalyst loading, with investigation into oxygen limitations. The product concentration and productivity were increased by keeping the substrate concentration below the inhibitory level via continuous substrate feeding (CSF). This substrate feeding strategy was evaluated against two biphasic reactions using either toluene or n-butyl acetate as immiscible organic solvents. A product concentration of 38 g L–1 and a space-time yield of 1.35 g L–1 h–1 were achieved during the gram-scale synthesis of the two regioisomeric lactones by applying the CSF strategy. These improvements contribute to the large-scale application of BVMOs in the synthesis of branched building blocks for polymer applications.
Original languageEnglish
Pages (from-to)803-812
Number of pages10
JournalOrganic Process Research & Development
Volume22
Issue number7
DOIs
Publication statusPublished - 20 Jul 2018

Keywords

  • BAEYER-VILLIGER MONOOXYGENASES
  • CYCLOHEXANONE MONOOXYGENASE
  • EPSILON-CAPROLACTONE
  • SCALE
  • OXIDATION
  • SOLUBILITY
  • POLYESTERS
  • CASCADE

Cite this

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title = "Toward Upscaled Biocatalytic Preparation of Lactone Building Blocks for Polymer Applications",
abstract = "Although Baeyer–Villiger monooxygenases (BVMOs) have gained attention in recent years, there are few cases of their upscaled application for lactone synthesis. A thermostable cyclohexanone monooxygenase from Thermocrispum municipale (TmCHMO) was applied to the oxidation of 3,3,5-trimethylcyclohexanone using a glucose dehydrogenase (GDH) for cofactor regeneration. The reaction progress was improved by optimizing the biocatalyst loading, with investigation into oxygen limitations. The product concentration and productivity were increased by keeping the substrate concentration below the inhibitory level via continuous substrate feeding (CSF). This substrate feeding strategy was evaluated against two biphasic reactions using either toluene or n-butyl acetate as immiscible organic solvents. A product concentration of 38 g L–1 and a space-time yield of 1.35 g L–1 h–1 were achieved during the gram-scale synthesis of the two regioisomeric lactones by applying the CSF strategy. These improvements contribute to the large-scale application of BVMOs in the synthesis of branched building blocks for polymer applications.",
keywords = "BAEYER-VILLIGER MONOOXYGENASES, CYCLOHEXANONE MONOOXYGENASE, EPSILON-CAPROLACTONE, SCALE, OXIDATION, SOLUBILITY, POLYESTERS, CASCADE",
author = "Marie Delgove and Matthew Elford and Katrien Bernaerts and {de Wildeman}, Stefaan",
year = "2018",
month = "7",
day = "20",
doi = "10.1021/acs.oprd.8b00079",
language = "English",
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journal = "Organic Process Research & Development",
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publisher = "American Chemical Society",
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Toward Upscaled Biocatalytic Preparation of Lactone Building Blocks for Polymer Applications. / Delgove, Marie; Elford, Matthew; Bernaerts, Katrien; de Wildeman, Stefaan.

In: Organic Process Research & Development, Vol. 22, No. 7, 20.07.2018, p. 803-812.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Toward Upscaled Biocatalytic Preparation of Lactone Building Blocks for Polymer Applications

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AU - Elford, Matthew

AU - Bernaerts, Katrien

AU - de Wildeman, Stefaan

PY - 2018/7/20

Y1 - 2018/7/20

N2 - Although Baeyer–Villiger monooxygenases (BVMOs) have gained attention in recent years, there are few cases of their upscaled application for lactone synthesis. A thermostable cyclohexanone monooxygenase from Thermocrispum municipale (TmCHMO) was applied to the oxidation of 3,3,5-trimethylcyclohexanone using a glucose dehydrogenase (GDH) for cofactor regeneration. The reaction progress was improved by optimizing the biocatalyst loading, with investigation into oxygen limitations. The product concentration and productivity were increased by keeping the substrate concentration below the inhibitory level via continuous substrate feeding (CSF). This substrate feeding strategy was evaluated against two biphasic reactions using either toluene or n-butyl acetate as immiscible organic solvents. A product concentration of 38 g L–1 and a space-time yield of 1.35 g L–1 h–1 were achieved during the gram-scale synthesis of the two regioisomeric lactones by applying the CSF strategy. These improvements contribute to the large-scale application of BVMOs in the synthesis of branched building blocks for polymer applications.

AB - Although Baeyer–Villiger monooxygenases (BVMOs) have gained attention in recent years, there are few cases of their upscaled application for lactone synthesis. A thermostable cyclohexanone monooxygenase from Thermocrispum municipale (TmCHMO) was applied to the oxidation of 3,3,5-trimethylcyclohexanone using a glucose dehydrogenase (GDH) for cofactor regeneration. The reaction progress was improved by optimizing the biocatalyst loading, with investigation into oxygen limitations. The product concentration and productivity were increased by keeping the substrate concentration below the inhibitory level via continuous substrate feeding (CSF). This substrate feeding strategy was evaluated against two biphasic reactions using either toluene or n-butyl acetate as immiscible organic solvents. A product concentration of 38 g L–1 and a space-time yield of 1.35 g L–1 h–1 were achieved during the gram-scale synthesis of the two regioisomeric lactones by applying the CSF strategy. These improvements contribute to the large-scale application of BVMOs in the synthesis of branched building blocks for polymer applications.

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KW - POLYESTERS

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