Exploring the Substrate Scope of Baeyer–Villiger Monooxygenases with Branched Lactones as Entry towards Polyesters

Delgove, Marie A. F.; Fürst, Maximilian J. L. J.; Fraaije, Marco W.; Bernaerts, Katrien V.; Wildeman, Stefaan M. A. De

doi:10.1002/cbic.201700427

Cited by 13 publications

(14 citation statements)

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“…The enzymatic synthesis of functionalized lactones, β,δ‐trimethyl‐ϵ‐caprolactones (TMCL), used as a monomer for polymeric applications, has previously been established (Figure ) . This product can be synthesized through two synthetic routes from the same cyclic ketone substrate 3,3,5‐trimethylcyclohexanone (TMCH).…”

Section: Introductionmentioning

confidence: 99%

A Prospective Life Cycle Assessment (LCA) of Monomer Synthesis: Comparison of Biocatalytic and Oxidative Chemistry

et al. 2019

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Biotechnological processes are typically perceived to be greener than chemical processes. A life cycle assessment (LCA) was performed to compare the chemical and biochemical synthesis of lactones obtained by Baeyer–Villiger oxidation. The LCA is prospective (based on experiments at a small scale with primary data) because the process is at an early stage. The results show that the synthesis route has no significant effect on the climate change impact [(1.65±0.59) kgCO2 gproduct−1 vs. (1.64±0.67) kgCO2 gproduct−1]. Key process performance metrics affecting the environmental impact were evaluated by performing a sensitivity analysis. Recycling of solvents and enzyme were shown to provide an advantage to the enzymatic synthesis. Additionally, the climate change impact was decreased by 71 % if renewable electricity was used. The study shows that comparative LCAs can be used to usefully support decisions at an early stage of process development.

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Section: Introductionmentioning

confidence: 99%

A Prospective Life Cycle Assessment (LCA) of Monomer Synthesis: Comparison of Biocatalytic and Oxidative Chemistry

et al. 2019

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“…insertion of one atom of oxygen at the most‐ or least‐substituted position, respectively). BVMOs display a broad substrate scope,4, 5 which include cyclic ketones with a heteroatom,6, 7 macrocyclic ketones,8, 9, 10, 11 and substituted derivatives of various ring size (for example, terpene‐based substrates12, 13). 14, 15 BVMOs are also especially interesting in the synthesis of branched lactones, from which branched aliphatic polyesters with low glass transition temperatures can be made 16, 17, 18, 19, 20, 21, 22, 23, 24, 25…”

Section: Introductionmentioning

confidence: 99%

“…This BVMO displays good thermostability ( T m = 48 °C) and very good solvent resistance, thus making it a good candidate for up‐scaled enzymatic oxidations. We recently reported on the broad substrate scope of TmCHMO with branched cyclic ketones including (+),(–)‐menthone, α,β‐thujone, jasmatone, and 3,3,5‐trimethylcyclohexanone 12. The products of the oxidation of 3,3,5‐trimethylcyclohexanone, which consist of a mixture of regio‐isomeric branched ϵ‐caprolactone derivatives, are of interest for the synthesis of aliphatic (co)polyesters 37, 38, 39…”

Section: Introductionmentioning

confidence: 99%

Application of a thermostable Baeyer–Villiger monooxygenase for the synthesis of branched polyester precursors

Delgove

Elford

Bernaerts

et al. 2018

J of Chemical Tech & Biotech

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BACKGROUNDIt is widely accepted that the poor thermostability of Baeyer–Villiger monooxygenases limits their use as biocatalysts for applied biocatalysis in industrial applications. The goal of this study was to investigate the biocatalytic oxidation of 3,3,5‐trimethylcyclohexanone using a thermostable cyclohexanone monooxygenase from Thermocrispum municipale (TmCHMO) for the synthesis of branched ϵ‐caprolactone derivatives as building blocks for tuned polymeric backbones. In this multi‐enzymatic reaction, the thermostable cyclohexanone monooxygenase was fused to a phosphite dehydrogenase (PTDH) in order to ensure co‐factor regeneration.RESULTSUsing reaction engineering, the reaction rate and product formation of the regio‐isomeric branched lactones were improved and the use of co‐solvents and the initial substrate load were investigated. Substrate inhibition and poor product solubility were overcome using continuous substrate feeding regimes, as well as a biphasic reaction system with toluene as water‐immiscible organic solvent. A maximum volumetric productivity, or space–time‐yield, of 1.20 g L‐1 h‐1 was achieved with continuous feeding of substrate using methanol as co‐solvent, while a maximum product concentration of 11.6 g L‐1 was achieved with toluene acting as a second phase and substrate reservoir.CONCLUSIONThese improvements in key process metrics therefore demonstrate progress towards the up‐scaled Baeyer–Villiger monooxygenase‐biocatalyzed synthesis of the target building blocks for polymer application. © 2018 The Authors. Journal of Chemical Technology & Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

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“…[89] Wild-type BVMO generally exhibits poor substrate selectivity and conversion towards monoterpene scaffolds. [69] To overcome this, Bornscheuer and coworkers identified three important residues in the active site that are thought to play a vital role in substrate binding and catalysis. The presence of dual alkene functionality in limonene makes it a versatile monomer that has been used in the synthesis of thermoplastic polymers and in coating applications.…”

Section: Monoterpenes As Highly Functionalized Monomersmentioning

confidence: 99%

Chemo-enzymatic routes towards the synthesis of bio-based monomers and polymers

Ahmed

Leferink

Scrutton

2019

Molecular Catalysis

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Scheme 7. Kinetic resolution of aromatic mandelic acid derivatives. Enantioselective hydrolysis of α-hydroxynitriles using nitrilases offer a facile approach to chiral hydroxy acids with theoretical yields of 100% in a dynamic kinetic resolution (DKR) process. Robertson et. al. identified 137 nitrilases after screening 651 environmental samples of which 44 were found to be (R) and 4 were (S)-selective on mandelonitrile. [36] Further investigation revealed nitrilase I and II to be proficient in the DKR of arylnitriles (rac-14 and 15) towards the synthesis of a panel of mandelic acid (R)-14 and phenyllactic acid derivatives (S)-15.[37] Scheme 8.Chemo-enzymatic DKR of α-hydroxynitriles towards the production of aromatic hydroxy acids. Dehydrogenases provide an alternative route to hydroxy acids via the asymmetric reduction of the pro-chiral ketone in α-keto esters. Fusion proteins consisting of glutathione Stransferase N-terminally linked to putative dehydrogenases from S. cerevisiae (Ypr1p and Gre1p) were used to reduce ethyl 2-oxo-4-phenylbutanoate to the corresponding alcohol with high enaniopurity.[38] Further systematic investigation by the same group on 18 reductases fused with GST showed activity towards α-and β-keto esters. [39] Five enzymes encoded from the yeast gene YDLI24w, YAL060w, YGL157w, YDR541c and YGL151w displayed excellent enantioselectivity across all three α-keto esters, affording the corresponding alcohol in >99% ee. Xu and co-workers engineered a highly stereoselective D-lactate dehydrogenase (D-LDH) towards a panel of aliphatic and aromatic αketoesters.[40] The Y52L mutant of D-LDH showed enhanced activity compared to the wildtype across the whole substrate panel (scheme 9). Scheme 9. Panel of α-keto acids using engineered D-lactate dehydrogenase (D-LDH). Values in brackets show % change in specific activity between wt and Y52L mutant.

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Exploring the Substrate Scope of Baeyer–Villiger Monooxygenases with Branched Lactones as Entry towards Polyesters

Cited by 13 publications

References 57 publications

A Prospective Life Cycle Assessment (LCA) of Monomer Synthesis: Comparison of Biocatalytic and Oxidative Chemistry

A Prospective Life Cycle Assessment (LCA) of Monomer Synthesis: Comparison of Biocatalytic and Oxidative Chemistry

Application of a thermostable Baeyer–Villiger monooxygenase for the synthesis of branched polyester precursors

Chemo-enzymatic routes towards the synthesis of bio-based monomers and polymers

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