Multi-reaction kinetic modeling for the peroxidase-aldolase cascade synthesis of a D-fagomine precursor
Masdeu, Gerard (Universitat Autònoma de Barcelona. Departament d'Enginyeria Química, Biològica i Ambiental)
Findrik Blažević, Zvjezdana (University of Zagreb)
Kralj, Slavko (Univerza V Ljubljani)
Makovec, Darko (Jožef Stefan Institute. Department for Materials Synthesis)
López Santín, Josep (Universitat Autònoma de Barcelona. Departament d'Enginyeria Química, Biològica i Ambiental)
Álvaro, Gregorio (Universitat Autònoma de Barcelona. Departament d'Enginyeria Química, Biològica i Ambiental)

Date:	2021
Abstract:	The feasibility of a peroxidase-aldolase cascade reaction for the synthesis of therapeutically-valuable iminocyclitols is discussed herein. A two-enzyme system consisting of chloroperoxidase (CPO) and D-fructose-6-phosphate aldolase (FSA) was evaluated for the synthesis of a D-fagomine precursor (preFagomine) from a N-Cbz-3-aminopropanol. An in-depth, systematic, step-by-step kinetic modeling of seven reactions and two inactivation decays was proposed to elucidate the reaction mechanism, prepare suitable stabilized biocatalysts, and find the optimal conditions for its application. The model described accurately the data and predicted the outcome at different experimental conditions. The inactivation of FSA caused by CPO was identified as the main bottleneck in the reaction. A two-step reaction approach and the use of immobilized enzymes on magnetic nanoparticle clusters and functionalized agarose carriers increased the stability of FSA, with an 1839-fold higher preFagomine formation per mol of enzyme in comparison to a one-pot reaction using soluble enzymes.
Grants:	Ministerio de Economía y Competitividad CTQ2014-53114R Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/SGR-452
Note:	Altres ajuts: acords transformatius de la UAB
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Enzymatic reaction cascade ; Peroxidase ; Aldolase ; D-fagomine ; Kinetic modeling
Published in:	Chemical Engineering Science, Vol. 239 (August 2021) , art. 116602, ISSN 0009-2509

DOI: 10.1016/j.ces.2021.116602

11 p, 2.2 MB

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