Katarzyna Szymańska, Klaudia Odrozek, Aurelia Zniszczoł, Wojciech Pudło, Andrzej B. JarzębskiChemical Engineering Journal, 315 (2017) 18-24 Keywords: Biotransformatio, Immobilized enzymes, Organic molecules, Scientific literature
Degradation of the pharmaceutical compound ibuprofen by ozone, was optimized in batch type reactors with and without zeolite based heterogeneous catalysts. The rotating bed reactor technology increased the concentrations of dissolved gas compared to traditional stirred tank reactors and allowed convenient handling of the catalyst particles without any filtration. Keywords: Fast reaction, Gas-distribution, Organic molecules, Scientific literature, Zeolite
A tutoral review taking a holistic approach to the engineering of biotransformations utilising isolated enzymes. The authors highlighted SpinChem® RBR technology benefits and wrote; “… in addition to protecting the biocatalyst from shear forces caused by the stirrer, it greatly accelerates mass transfer, thus affording substantially higher reaction rates and creating the possibility to use much smaller reactors”. Keywords: Biotransformation, Immobilized enzymes, Organic molecules, Review, Scientific literature
Tung Ngoc Pham, Ajaikumar Samikannu, Anne-Riikka Rautio, Koppany L. Juhasz, Zoltan Konya, Johan Wärnå, Krisztian Kordas, Jyri-Pekka MikkolaTopics in Catalysis, 59 (2016) 1165-1177
A rotating bed reactor containing ion exchange beads was modeled in flower-baffled reaction vessels. It was shown that the baffles are vital for reducing surface vortexes and circular flow within the vessel. The authors concluded that the flow rates through the packed bed and reaction rates tend to increase with deeper baffles. Keywords: Ion exchange, Scientific literature, Simulation, Technology
Valerie Eta, Jyri-Pekka MikkolaCarbohydrate Polymers, 136 (2016) 459-465
In line with the call for sustainable production, researchers are focusing their efforts on the utilization of renewable resources and the development of environmentally friendly manufacturing methods. Bio-based polymers are emblematic and has potential in terms of polymerization and material characteristics. Many products are using hydroxystyrene monomer these days. Hydroxystyrenes are particularly appealing as a replacement or addition to styrene-based polymer chemistry since they are renewable lignin building blocks. These monomers are made by decarboxylating phenolic acids, and their phenolic hydroxy groups are frequently subjected to chemical changes to enhance polymerization behavior. A straightforward, scalable, and entirely (chemo)catalytic synthesis of acetylated hydroxystyrene is still difficult to come by. With functionalized polystyrene's range and potential, the question arises of how scalable and sustainable the respective monomers are that can be synthesized? Contributing to answering the above question we will discuss a recent research project INTERfaces that developed a green, one-pot, two-step approach to producing acetylated hydroxystyrenes from raw lignin. In this case, the acylated hydroxystyrenes were designed as environmentally friendly monomers for making certain polystyrenes. Also, authors suggestions on a novel chemoenzymatic pathway that uses phenolic acid decarboxylase (PAD) would be discussed. A novel chemoenzymatic pathway Authors suggest a novel chemoenzymatic pathway that makes use of a phenolic acid decarboxylase (PAD). Authors have hypothesized that limitations could be circumvented by a tailored combination of a more active decarboxylation catalyst, milder reaction conditions and a compatible reaction medium. As a renewable, non-toxic, and highly active catalyst, phenolic acid decarboxylase from Bacillus subtilis (BsPAD) was the biocatalyst of our choice to embark on this process development. Herein, we describe our systematic efforts to design an alternative, scalable, chemo-enzymatic route to access bio-based styrene alternatives in an environmentally friendly and efficient manner. An approach to process development entails a computational solvent assessment that provides information on solubilities and feasible reactor operation modes, experimental solvent screening, cascade engineering, heterogenization of biocatalyst, customization of acetylation conditions, and reaction upscale in a rotating bed reactor. Procedure Decarboxylation of phenolic acids, which can be generated from lignin, to the equivalent hydroxystyrene is the initial step. As a green decarboxylation catalyst, phenolic acid decarboxylase from Bacillus subtilis (bsPAD) was used. A significant amount of computational and experimental work was put into finding a solvent and water saturation that allowed for high enzyme catalytic activity in the non-conventional media while also offering good solubility of the phenolic acid reactant and hydroxystyrene product. MTBE and CPME that were water-saturated had all required characteristics. The more eco-friendly option was CPME because of higher boiling point, which was beneficial in the second step. The hydroxystyrene intermediate was directly acylated without switching solvents in the second stage of the one-pot, two-step synthesis. The effectiveness of the acylation of the phenol in a wet solvent was confirmed. The ideal parameters for an experiment were found to be low catalyst concentrations (0.03 eq NaOAc), moderate anhydride concentrations (2.0 eq Ac2O), and relatively high temperatures (90°C). The enzyme bsPAD was immobilized to allow for reuse and to stop it from obstructing the second step and work-up. Immobilization on Purolite ECR8415F as a carrier material was the outcome of extensive evaluation of enzyme carrier materials and chemistries for high immobilization yield, enzymatic activity, and longevity. Using the RBR The reaction was scaled up to 1 L to prove its feasibility. SpinChem RBR S3 was used to charge the immobilized bsPAD-8415F enzyme for the reaction. The application of RBR, resulted in a developed clean, one-pot, two-step procedure that makes use of bio-based phenolic acid educts, reusable immobilized PAD, and the renewable solvent CPME. On a 1 L scale, the entire chemoenzymatic reaction casscadded to produce 18.3 g of 4-acetoxy-3-methoxystyrene with a 96% isolated yield. As a result of the rotating bed reactor, the carrier beads were protected and the enzyme could be simply removed between steps one and two, thus preventing the enzyme from interfering with the second step and to be reused in the decarboxylation step. The RBR made the process fast and simple, provided efficient sampling and monitoring of the process and kept the immobilized catalyst safely confined. Interested in the rotating bed reactor? Get in touch with us to understand how the rotating bed reactor technology can simplify or improve your process.
Hendrik Mallin, Jan Muschiol, Dr. Emil Byström, Prof. Dr. Uwe T. BornscheuerChemCatChem, 5 (2013) 3529-3532 "...the immobilized transaminase was better protected from mechanical forces in the SpinChem device." Keywords: Alginate, Biotransformation, Encapsulated cells, Immobilized enzymes, Organic molecules, Scientific literature
Valerie Eta, Ikenna Anugwom, Pasi Virtanen, P. Mäki-Arvelaa, Jyri-Pekka MikkolaIndustrial Crops and Products, 55 (2014) 109-115 Keywords: Scientific literature
Epoxidation reactions with in-situ formed percarboxylic acids were enhanced by heterogeneous catalysis and optimized with respect to product yield. The authors concluded that “SpinChem RBR, was beneficial, in terms of eliminating mass transfer limitations, it enabled a simpler collection and recycling of the catalyst and minimized mechanical wear of the solid catalyst”. Keywords: Easy handling, Ion exchange, Organic molecules, Scientific literature, Synthesis
Ran Duan, Bo S. Westerlind, Magnus Norgren, Ikenna Anugwom, Pasi Virtanen, Jyri-Pekka MikkolaBioResources, 11 (2016) 8570-8588
Water is an important factor in enzymatic reactions as it affects the enzyme activity and the equilibrium position of hydrolytic reactions. To study these effects, the authors first developed a system based on relatively simple and low-cost components that could continuously control the activity of water in organic media in a SpinChem® RBR. Structured lipids with desired properties can be produced by enzymatic transesterification. This is a multistep reaction with many factors influencing both the product yield and quality. In this study, the single and combined effects of water activity, temperature and substrate ratio were studied on the reaction between high oleic sunflower oil and ethyl stearate. The efficient mixing in the RBR also in viscous solutions such as oil, further improves the dispersion of nitrogen gas and the mass transfer rate. A system to control the thermodynamic water activity in the range of 0.05–0.92 in a 0.12–0.3 L RBR from SpinChem® (Umeå, Sweden) was developed. A schematic drawing of the system is presented in the figure above. The reactor is a jacketed glass reactor (SpinChem® V2) with a rotating bed (SpinChem® S2) for agitation and compartmentalization of immobilized enzymes.
Ikenna Anugwoma, Luis Rujana, Johan Wärnå, Mattias Hedenström, Jyri-Pekka MikkolaChemical Engineering Journal, 297 (2016) 256–264
The present work reports on the production of extracellular l-asparaginase from Rhizopus microsporus IBBL-2 using submerged fermentation (SmF) process free of glutaminase and urease activities. Scale-up studies involving 200-mL and 1-L rotating bed reactor (RBR) using immobilized beads were done and the results obtained are 20.21 U mL-1 and 19.13 U mL-1, respectively, the increased activity with immobilization accounts for reduced shear on cells due to increased stability as compared to the free-flowing cells.
A synthesis of N-Boc (2R)-1,4-oxazepane-2-carboxylic acid was developed in 39% yield over seven steps starting from methyl (2R)-glycidate. The key step was a lipase-catalyzed regioselective lactamization performed using SpinChem® rotating bed reactor that simplified work up and recycling of the enzyme. Carl-Johan Aurell*, Staffan Karlsson, Fritiof Pontén, and Søren M. Andersen Keywords: Biotransformation, Immobilized enzymes, Organic molecules, Quick recycling, Scientific literature
Jochen Wachtmeister, Philip Mennicken, Andreas Hunold, Dörte RotherChemCatChem, 8 (2016) 607-614 Keywords: Biotransformation, Encapsulated cells, Organic molecules, Scientific literature
In the American Institute of Chemical Engineers, AIChE Journal, the authors of this paper highlights the use of Rotating Bed Reactor (RBR) with two different immobilized enzymes at the same time in a cascade reaction. In the flow chart above of the miniplant consisting of a continuously stirred tank reactor (CSTR) equipped with an RBR (highlighted in orange) (a), a buffer tank (b), an extractive centrifuge (c) and a fixed bed reactor (d) In the reaction scheme the complete multi-enzyme cascade is shown with the two enzymes placed in the RBR is highlighted. If you would like to get in contact with us give us a call or fill in the form.
An interesting paper where the authors mentions ”A further refinement, the rotating bed reactor developed by SpinChem... This technology combines the benefits of an STR and a packed bed and has been scaled up successfully to more than 100 litres scale.” Key learnings from the paper (1) The advantages and limitations of immobilised enzymes in industrial applications (2) The different technical and regulatory requirements using immobilised enzymes (3) The different enzyme immobilisation methods (4) The different reactor technologies for immobilised enzymes and biocatalysis in general (5) Recent advances in enzyme immobilisation for better production economy
In biotransformations, obstacles commonly encountered are product inhibition, product toxicity, and reaction equilibria that prevents complete conversion. Enzyme engineering has made tremendous progress in alleviating these problems. The concept of in situ product removal (ISPR) may still be an attractive alternative or complement. The authors have demonstrated concurrent enzymatic reaction and ISPR, referred to as 'extractive biocatalysis'. For the ISPR, the authors evaluated the use of aqueous micellar two-phase systems (ATPMS) as an extraction medium. For the model reaction, Penicillin G hydrolysis by CalB lipase, the demonstrated process was thus a continuous, heterogeneous extractive biocatalysis with cloud point extraction. An RBR was used during the process development work to determine the Michaelis-Menten kinetics of the CalB immobilized in gel coatings on column packing material. Also, the particles were easily re-used in stability experiments.
The paper describes work to valorize olive leaves, the major by-product in olive oil production. Aqueous olive leaf extract is rich in oleuropein that was enzymatically hydrolyzed by beta-glucosidase to hydroxytyrosol and other products. Compared to the non-modified extract, the modified one demonstrated 20% higher antioxidant activity, seven-fold higher antibacterial activity, and enhanced cytotoxicity against leiomyosarcoma cells. The beta-glucoside was immobilized in chitosan-coated magnetic beads and used in both stirred tank reactor (STR) and rotating bed reactor (RBR). The immobilized enzyme showed good stability over time and the activity was good in both STR and RBR settings. However, the enzyme beads were damaged mechanically in the STR and could not be re-used. The RBR solved the problem of bead attrition allowing the immobilized enzyme to be re-used and thus giving superior total turnover number to the STR.
The paper describes the author’s successful work to express and use recombinant choline oxidase. The gene for the choline oxidase was isolated from a Gram-positive soil bacterium, cloned into an expression vector, inserted into and overexpressed in a Rosetta expression system. The isolated recombinant choline oxidase was subsequently immobilized onto Ni-Sepharose beads, which were loaded in a rotating bed reactor (RBR). With the immobilized choline oxidase in the RBR, reaction conditions such as pH and temperature were optimized and the enzymatic activity measured for the reaction of choline to glycine betaine via betaine aldehyde.
Pobitra Halder, Sazal Kundu, Savankumar Patel, Adi Setiawan, Rob Atkin, Rajarathinam Parthasarthy, Jorge Paz-Ferreiro, Aravind Surapaneni, Kalpit ShahRenewable and Sustainable Energy Reviews, 105 (2019) 268-292 The paper refers to SpinChem Application L1603, with this quote "The model was analysed and optimised using Modest™ software and it was found that the ® SpinChem rotating bed reactor was the most promising reactor in term of lignin dissolution when compared to the non-stirring batch reactor and the loop reactor." Keywords: Scientific literature
This article involves the use of a rotating bed reactor for a biocatalytic process involving biofilms. The biofilm of Pseudomonas taiwanensis, with a genetically introduced Baeyer-Villiger monooxygenase (BVMO), was grown directly on 3D-printed polyamide inserts installed in the RBR S3. The biofilm, immobilized on the cartridges, was then used to catalyze the conversion of cyclohexanone. The authors comment that the work opens up the possibility to use biofilms in rotating bed reactors for synthesis via biocatalysis.
A traditional stirred tank reactor setup was compared to a rotating bed reactor (RBR) for the biocatalytic synthesis of the anti-inflammatory drug (S)-naproxen. Both setups performed well during five repetitive bathes giving an enantiomeric excess of 99% and an isolated yield of 92%, but the RBR was easier to handle and the authors concluded that “… the rotating bed reactor concept can be regarded as a promising option for industrial applications”. Keywords: Biotransformation, Immobilized enzymes, Organic molecules, Scientific literature
Jochen Wachtmeister, Dörte RotherCurrent Opinion in Biotechnology, 42 (2016) 169-177 Keywords: Biotransformation, Encapsulated cells, Organic molecules, Scientific literature
A comprehensive review of biocatalysis covering how the recent advances in engineering of enzymes, substrates, media and reactor design contributes to a sustainable chemistry development. The authors wrote that SpinChem® RBR technology “combines the advantages of a stirred tank with those of a packed bed” thus giving benefits by “circumventing mechanical attrition of the biocatalyst” while “mass transfer is greatly accelerated”. Keywords: Biotransformation, Immobilized enzymes, Organic molecules, Review, Scientific literature
Correlation data between extracted anthocyanidins/ anthocyanins vs time, temperature, and ethanol concentration was collected and analyzed. RBR extraction was deemed advantageous, in the authors’ own words: “The RBR was better than traditional extraction and 16 min sufficed.” Bilberry press cake is the major by-product from the production of bilberry juice. To valorize the press cake, the authors describe their work to extract antioxidant antocyanidins/ antocyanins from the cake. Different solvent compositions were compared as well as traditional extraction vs extraction by use of RBR. The methods used were as follows: “To summarize, the compared extraction methods were as follows: 1. Traditional extraction using different concentrations of ethanol dissolved in water, different masses of material, and different temperatures. 2. RBR extraction using different concentrations of ethanol dissolved in water, different masses, and temperatures. 3. RBR extraction using two-phase system, method 3 only mass and temperature were changed. 4. RBR extraction using two-phase system method 4, only mass and temperature were changed.”
Subhash Pithani, Staffan Karlsson, Hans Emtenäs, and Christopher T. ÖbergOrganic Process Research & Development 2019 23 (9), 1926-1931 "By using SpiChem RBR technology, we found that recycling of the immobilized enzyme was easy with preserved enantioselectivity and catalytic activity. The final optimized process was successfully demonstrated on a 1 kg scale with 39% isolated yield and 98.8% enantiomeric purity." Keywords: Scientific literature
This scientific minireview highlights that “one-pot multi-catalysis reactions is a revolutionary tool for multistep synthesis” and that “reaction engineering is indispensable to further advance biotransformation processes”. The authors concluded that “advanced reactor design such as … the SpinChem reactor, could also enhance cascade biotransformation processes”. Keywords: Biotransformation, Encapsulated cells, One-pot multistep, Review, Scientific literature
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