Biocatalytic redox reactions regularly depend on expensive cofactors that require recycling. For continuous conversions in flow chemistry, this is often an obstacle since the cofactor is washed away. Here, we present a quasi-stationary recycling system for nicotinamide adenine dinucleotide phosphate utilizing an immobilized alcohol dehydrogenase. Four model substrates were reduced with high enantioselectivity as a proof of concept. The two-phase system enables continuous production as well as quick substrate changes. This setup may serve as a general cofactor regeneration module for continuous biocatalytic devices employing (co-)substrates being miscible in organic solvent. The system resulted in space-time yields up to 117 g L À 1 h À 1 and total turnover numbers for nicotinamide adenine dinucleotide phosphate higher than 12,000 mol/mol are possible.
In industries, enzymes are often immobilized to obtain stable preparations that can be utilized in batch and flow processes. In contrast to traditional immobilization methods that rely on carrier binding, various immobilization strategies have been recently presented that enable the simultaneous production and in vivo immobilization of enzymes. Catalytically active inclusion bodies (CatIBs) are a promising example for such in vivo enzyme immobilizates. CatIB formation is commonly induced by fusion of aggregation-inducing tags, and numerous tags, ranging from small synthetic peptides to protein domains or whole proteins, have been successfully used. However, since these systems have been characterized by different groups employing different methods, a direct comparison remains difficult, which prompted us to benchmark different CatIB-formation-inducing tags and fusion strategies. Our study highlights that important CatIB properties like yield, activity, and stability are strongly influenced by tag selection and fusion strategy. Optimization enabled us to obtain alcohol dehydrogenase CatIBs with superior activity and stability, which were subsequently applied for the first time in a flow synthesis approach. Our study highlights the potential of CatIB-based immobilizates, while at the same time demonstrating the robust use of CatIBs in flow chemistry.
Background and Objectives: The hemoadsorption device CytoSorb® (CytoSorbents Inc., Princeton, NJ, USA) has been shown to efficiently remove ticagrelor from whole blood in vitro. A promising clinical experience was made with the integration of the hemoadsorption cartridge on the cardiopulmonary bypass (CPB) circuit during cardiac surgery to reduce adverse events. Materials and Methods: In this report, we describe a novel approach using a new apheresis platform, PUR-01 (Nikkisio Co., Ltd., Tokyo, Japan), which was used as the extracorporeal circuit where CytoSorb® could be installed for the removal of ticagrelor during off-pump coronary artery bypass (OPCAB) procedures. Results: In a 74-year-old male (index case) with coronary artery disease and dual antiplatelet therapy, hemoadsorption was initiated with a skin incision for OPCAB surgery and was continued for 221 min to eliminate ticagrelor. The blood volume that had circulated through the CytoSorb® was 39.04 L in total. Thus far, this treatment strategy has been used in four cases with CHD and DAPT who needed OPCAB surgery. The intraoperative and postoperative courses were uneventful in all patients. No device-related adverse events occurred. Conclusions: The combination of the PUR-01 apheresis pump and hemoadsorption with the CytoSorb® column during OPCAB procedures appears to be safe and effective in eliminating antiplatelet drugs.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.