Enzyme synthesis of cephalexin in continuous-flow microfluidic device in ATPS environment

Vobecká, Lucie; Tichá, Linda; Atanasova, Aleksandra; Slouka, Zdeněk; Hasal, P.; Přibyl, Michal

doi:10.1016/j.cej.2020.125236

Cited by 39 publications

(23 citation statements)

References 46 publications

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“…103 Vobecká et al have recently presented an interesting work in which they present an enzymatic synthesis of cephalexin in a continuous-flow microfluidic device in aqueous two-phase system (ATPS) forming twophase slug flow in a microfluidic capillary as the reactionseparation environment. 104 ATPS consisted of 15 wt% of PEG 4000, 12 wt% of phosphates, and 73 wt% of water.…”

Section: Reaction Chemistry and Engineering Reviewmentioning

confidence: 99%

The rise of continuous flow biocatalysis – fundamentals, very recent developments and future perspectives

2020

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Section: Reaction Chemistry and Engineering Reviewmentioning

confidence: 99%

The rise of continuous flow biocatalysis – fundamentals, very recent developments and future perspectives

2020

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“…2020, 396, 125236. 75 thus phase separation problems, this obstacle is reduced in microflow reactors. 39,78 Applications of slug flow include various reactions and enzymes, from reactions catalyzed by alcohol-dehydrogenase (ADH), [79][80][81][82] to hydroxynitrile lyase-catalyzed C-C bond formation, 83 a reduction with pentaerythritol tetranitrate reductase, 84 terpene production catalyzed by aristolochene synthase, 77 penicillin acylase-catalyzed antibiotic synthesis, 75,85,86 and lipase-assisted biodiesel production, 87,88 among others.…”

Section: Segmented-flow Microreactors With Biocatalystsmentioning

confidence: 99%

Let the Biocatalyst Flow

Žnidaršič–Plazl

2021

ACSi

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Industrial biocatalysis has been identified as one of the key enabling technologies that, together with the transition to continuous processing, offers prospects for the development of cost-efficient manufacturing with high-quality products and low waste generation. This feature article highlights the role of miniaturized flow reactors with free enzymes and cells in the success of this endeavor with recent examples of their use in single or multiphase reactions. Microfluidics-based droplets enable ultrahigh-throughput screening and rapid biocatalytic process development. The use of unique microreactor configurations ensures highly efficient contacting of multiphase systems, resulting in process intensification and avoiding problems encountered in conventional batch processing. Further integration of downstream units offers the possibility of biocatalyst recycling, contributing to the cost-efficiency of the process. The use of environmentally friendly solvents supports effective reaction engineering, and thus paves the way for these highly selective catalysts to drive sustainable production.

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“…Methanol Free enzyme PA EC 3.6.1.11 (Creative Enzymes NATE-0541) was used in the reaction experiments. We used the enzyme solution from the same batch (frozen for long-term storage) as in our previous work (Vobecká et al, 2020). The obtained activity was about 2.88 kU/ml of the enzyme stock, where 1 U was defined as the amount of the enzyme hydrolyzing 1 μmol of PenG per 1 min at pH 8.0°C and 37°C in 0.01 M phosphate buffer.…”

Section: Chemicalsmentioning

confidence: 99%

“…Here, we introduce a sandwich-type microfluidic device for continuous and highly efficient separation of 6-aminopenicillanic acid (6-APA) and phenylacetic acid (PAA) from a mixture containing soluble penicillin acylase (PA). This choice of the enzyme reaction reflects our effort to develop processes for the continuous production of pharmaceuticals and special chemicals (Mařík et al, 2020;Vobecká et al, 2018Vobecká et al, , 2020. PA hydrolyzes Penicillin G (PenG) to PAA and 6-APA.…”

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confidence: 99%

Electric‐field‐enhanced selective separation of products of an enzymatic reaction in a membrane micro‐contactor

Romanov

Slouka

Přibyl

2020

Biotech & Bioengineering

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Processes employed in separations of products of enzyme reactions are often driven by diffusion, and their efficiency can be limited. Here, we exploit the effect of a direct current (DC) electric field that intensifies mass transfer through a semipermeable membrane for fast, continuous, and selective separation of electrically charged molecules. Specifically, we separate low‐molecular‐weight reaction products (phenylacetic acid, 6‐aminopenicillanic acid) from the original reaction mixture containing a free enzyme (penicillin acylase). The developed microfluidic dialysis‐membrane contactor allows a stable counter‐current arrangement of the retentate and permeates liquid streams on which DC electric field is perpendicularly applied. The applied electric field significantly accelerates the transport of electrically charged products through the semipermeable membrane yielding high separation efficiencies at short residence times. The residence time of 5 min is sufficient to reach 100% separation yield in the electric field. The same residence time provides only a 50% yield in the diffusion‐controlled experiments. We experimentally demonstrated that a combined microreactor–microextractor with a recycle of the soluble penicillin acylase can continuously produce both the reaction products at high concentrations. The developed membrane‐contactor is a versatile platform allowing to tune its characteristics, such as selectivity given by the membrane, or the type of the retentate phase, for a specific application.

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Enzyme synthesis of cephalexin in continuous-flow microfluidic device in ATPS environment

Cited by 39 publications

References 46 publications

The rise of continuous flow biocatalysis – fundamentals, very recent developments and future perspectives

The rise of continuous flow biocatalysis – fundamentals, very recent developments and future perspectives

Let the Biocatalyst Flow

Electric‐field‐enhanced selective separation of products of an enzymatic reaction in a membrane micro‐contactor

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