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Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/214307

Computer Simulation to Rationalize "Rational" Engineering of Glycoside Hydrolases and Glycosyltransferases

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Glycoside hydrolases and glycosyltransferases are the main classes of enzymes that synthesize and degrade carbohydrates, molecules essential to life that are a challenge for classical chemistry. As such, considerable efforts have been made to engineer these enzymes and make them pliable to human needs, ranging from directed evolution to rational design, including mechanism engineering. Such endeavors fall short and are unreported in numerous cases, while even success is a necessary but not sufficient proof that the chemical rationale behind the design is correct. Here we review some of the recent work in CAZyme mechanism engineering, showing that computational simulations are instrumental to rationalize experimental data, providing mechanistic insight into how native and engineered CAZymes catalyze chemical reactions. We illustrate this with two recent studies in which (i) a glycoside hydrolase is converted into a glycoside phosphorylase and (ii) substrate specificity of a glycosyltransferase is engineered toward forming O-, N-, or S-glycosidic bonds.

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COINES, Joan, et al. Computer Simulation to Rationalize "Rational" Engineering of Glycoside Hydrolases and Glycosyltransferases. Journal of Physical Chemistry B. 2022. Vol. 126, num. 4, pags. 802-812. ISSN 1520-6106. [consulted: 15 of August of 2026]. Available at: https://hdl.handle.net/2445/214307

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