Continuous biphasic enzymatic reduction of aliphatic ketones

Leuchs, Susanne; Nonnen, Thomas; Dechambre, Dominique; Na’amnieh, Shukralla; Greiner, Lasse

doi:10.1016/j.molcatb.2012.09.017

Cited by 8 publications

(12 citation statements)

References 38 publications

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“…The conversions for all substrates are similar in contrast to Leuchs et al, 20 where a decrease in conversion was observed when 2-heptanone (X = 49%), 2-octanone (X = 31%), or 2-nonanone (X = 24%) were used as substrates.…”

Section: Continuous Synthesessupporting

confidence: 74%

“…However, with increasing chain length and decreasing solubility or increasing partitioning, respectively, the conversion and the space-time-yield (STY) dropped dramatically. 20 A monophasic solubiliser-aided approach seemed to be more suitable for the conversion of substrates with very low aqueous solubility. 13 The aim of our study was to assess continuous process conditions for the enantioselective reduction of hardly water-soluble ketones with integrated product separation and the reuse of the substrate solution after product-removal by SPE.…”

Section: Resultsmentioning

confidence: 99%

“…A high excess of 2-propanol is normally necessary when using a substrate-coupled approach. 20 The Fig. 1 Reaction system for the enantioselective reduction of aliphatic ketones.…”

Section: Resultsmentioning

confidence: 99%

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Enantioselective reduction of sparingly water-soluble ketones: continuous process and recycle of the aqueous buffer system

2013

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Section: Continuous Synthesessupporting

confidence: 74%

Section: Resultsmentioning

confidence: 99%

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Enantioselective reduction of sparingly water-soluble ketones: continuous process and recycle of the aqueous buffer system

2013

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“…The conversion to the reduced or oxidized form of NADH was recorded by monitoring the absorbance at 340 nm in a UV‐VIS spectrophotometer, Ultrospec 2100 pro. For each enzyme the denaturation constant, k D was determined assuming first order exponential decay (Leuchs, Nonnen, Dechambre, Na'amnieh, & Greiner, ).…”

Section: Methodsmentioning

confidence: 99%

Kinetics based reaction optimization of enzyme catalyzed reduction of formaldehyde to methanol with synchronous cofactor regeneration

Marpani

Sárossy

Pinelo

et al. 2017

Biotech & Bioengineering

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Enzymatic reduction of carbon dioxide (CO ) to methanol (CH OH) can be accomplished using a designed set-up of three oxidoreductases utilizing reduced pyridine nucleotide (NADH) as cofactor for the reducing equivalents electron supply. For this enzyme system to function efficiently a balanced regeneration of the reducing equivalents during reaction is required. Herein, we report the optimization of the enzymatic conversion of formaldehyde (CHOH) to CH OH by alcohol dehydrogenase, the final step of the enzymatic redox reaction of CO to CH OH, with kinetically synchronous enzymatic cofactor regeneration using either glucose dehydrogenase (System I) or xylose dehydrogenase (System II). A mathematical model of the enzyme kinetics was employed to identify the best reaction set-up for attaining optimal cofactor recycling rate and enzyme utilization efficiency. Targeted process optimization experiments were conducted to verify the kinetically modeled results. Repetitive reaction cycles were shown to enhance the yield of CH OH, increase the total turnover number (TTN) and the biocatalytic productivity rate (BPR) value for both system I and II whilst minimizing the exposure of the enzymes to high concentrations of CHOH. System II was found to be superior to System I with a yield of 8 mM CH OH, a TTN of 160 and BPR of 24 μmol CH OH/U · h during 6 hr of reaction. The study demonstrates that an optimal reaction set-up could be designed from rational kinetics modeling to maximize the yield of CH OH, whilst simultaneously optimizing cofactor recycling and enzyme utilization efficiency.

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“…Alcohol dehydrogenase from Lactobacillus brevis ( Lb ADH, EC 1.1.1.2) exhibits outstanding enantioselectivity, robustness, and flexibility in a wide variety of reaction conditions . The substrate scope of this enzyme is broad, and its ability to convert long-chain aliphatic ketones into the desired ( R )-2-alcohols has been proven in many batch syntheses, , as well as in monophasic, , and biphasic − continuous experiments. Water-solubility restrictions in single-phase approaches can be overcome by applying an ionic liquid (IL) as a solubiliser. ,, Kinetics , and stability tests , reveal the applicability of Lb ADH in many processes.…”

Section: Resultsmentioning

confidence: 99%

Reaction Engineering of Biocatalytic Enantioselective Reduction: A Case Study for Aliphatic Ketones

Leuchs

Lima-Ramos

Greiner

et al. 2013

Org. Process Res. Dev.

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Previously, it could be demonstrated, that the monophasic, enzymatic reduction of aliphatic 2-ketones into the corresponding (R)-2-alcohols is an adequate and viable method as carried out in a cascade of two enzyme−membrane reactors (Leuchs, S.; Na'amnieh, S. N.; Greiner, L. Green Chemistry 2013, 15, 167−176.). In the present work, the process metrics of the ketone reduction were calculated. A cost analysis revealed that the enzyme costs are negligible, but the cost for nicotinamide cofactor NADP + is dominating the overall cost of the chemical raw material followed by the ionic liquid (TEGO IL K5) used as solubiliser and the buffer. The overall cost of chemicals was €148/kg product . To assess the environmental impact of the process, the E-factor (kg waste /kg product ) 132 and the process mass intensity 133 (PMI, kg substrate /kg product ) were calculated. A process model based on initial rate experiments was elaborated and used to improve the process under cost and environmental aspects. Applying several measures to enhance the cofactor utilisation, the cost base could be reduced by 65% and the E-factor (PMI) to 17 (18).

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Continuous biphasic enzymatic reduction of aliphatic ketones

Cited by 8 publications

References 38 publications

Enantioselective reduction of sparingly water-soluble ketones: continuous process and recycle of the aqueous buffer system

Enantioselective reduction of sparingly water-soluble ketones: continuous process and recycle of the aqueous buffer system

Kinetics based reaction optimization of enzyme catalyzed reduction of formaldehyde to methanol with synchronous cofactor regeneration

Reaction Engineering of Biocatalytic Enantioselective Reduction: A Case Study for Aliphatic Ketones

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