engleski

Simulation of a two-step cascade reaction to yield (R)-4-chloro-3-hydroxybutyronitrile

In comparison with traditional organic synthesis methods, cascade multi-step biocatalytic reactions have many advantages. A few of them are sustainability, simple and cheaper reactor set- up, mild reaction conditions and lower environmental impact. [1, 2] Advancements in biocatalytic processes are achieved through reaction engineering. Combined kinetic and reactor modelling can significantly contribute to the choice of reactor mode, design and optimal operating conditions. [3, 4] Using modelling and simulations helps us study the effects of different variables on the process, which increase our knowledge and understanding of the system. [5] In this work, a two-step cascade reaction was studied (Figure 1). Both steps are catalysed by halohydrin dehalogenase (HheB2), mutant T120A. The first reaction was a ring closure of a substrate 1, 3-dichloro-2-propanol (DCP) to (R)- epichlorohydrin (ECH). The second reaction was ring-opening of (R)-ECH to (R)-4-chloro-3- hydroxybutyronitrile (HBN) with cyanide ion (CN-) as a nucleophile. (R)-HBN is a precursor to many valuable chemicals, such as L- carnitine, which plays a vital role in human metabolism. [6, 7] By using mathematical modelling and simulations, optimal reaction conditions were found for this system. Kinetics research has shown that the best results are achieved when both reaction steps are carried out simultaneously in one pot reaching the maximum product yield, and shifting the equilibrium to the right side. High product concentrations cannot be achieved in a batch reactor because of the substrate inhibition. However, in the fed-batch reactor concentrations of the inhibitors can be controlled which makes it an ideal solution. Funding: European Structural and Investment Funds, KK.01.1.1.04. References [1] M. Sudar, Z. Findrik Blažević, Enzyme Cascade Kinetic Modelling, Enzyme Cascade Design and Modelling, editors: S. Kara, F. Rudroff, Springer International Publishing, 2021, 91-108. [2] M. Česnik et al. Chemical Engineering Research and Design, 2019, 150, 140-152. [3] Đ. Vasić Rački et al. Applied Microbiology and Biotechnology, 2011, 91, 845-856. [4] Đ. Vasić Rački et al. Chemical and Biochemical Engineering Quarterly, 2003, 17(1), 3-14. [5] M. Sudar et al. Journal of Biotechnology, 2018, 268, 71-80. [6] T. Suzuki et al. Bioorganic & Medicinal Chemistry Letters, 1996, 6, 2581-2584. [7] Z. Findrik Blažević et al. Advanced Synthesis & Catalysis, 2021, 363(2), 388-410.

Cascade reaction ; (R)-4-chloro-3-hydroxybutyronitrile ; simulation

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