TY - JOUR
T1 - Computer Simulation to Rationalize "Rational" Engineering of Glycoside Hydrolases and Glycosyltransferases
AU - Coines, Joan
AU - Cuxart, Irene
AU - Teze, David
AU - Rovira, Carme
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
U2 - 10.1021/acs.jpcb.1c09536
DO - 10.1021/acs.jpcb.1c09536
M3 - Journal article
C2 - 35073079
SN - 1520-6106
VL - 126
SP - 802
EP - 812
JO - Journal of Physical Chemistry Part B: Condensed Matter, Materials, Surfaces, Interfaces & Biophysical
JF - Journal of Physical Chemistry Part B: Condensed Matter, Materials, Surfaces, Interfaces & Biophysical
IS - 4
ER -