1. How To Break the Janus Effect of H2O2 in Biocatalysis? Understanding Inactivation Mechanisms To Generate more Robust Enzymes
- Author
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Yonghua Wang, Lan Dongming, Uwe T. Bornscheuer, Frank Hollmann, Bo Yang, Tan Xiyu, and Ze Xin Zhao
- Subjects
inorganic chemicals ,chemistry.chemical_classification ,biology ,010405 organic chemistry ,QM/MM MD ,H O ,General Chemistry ,Protein engineering ,010402 general chemistry ,01 natural sciences ,Chemical synthesis ,Combinatorial chemistry ,Catalysis ,0104 chemical sciences ,Enzyme ,chemistry ,Biocatalysis ,epoxidation ,lipase ,biology.protein ,inactivation ,Janus ,Lipase ,multiscale MD - Abstract
H 2 O 2 , is an attractive oxidant for synthetic chemistry, especially if activated as percarboxylic acid. H 2 O 2 , however, is also a potent inactivator of enzymes. Protein engineering efforts to improve enzyme resistance against H 2 O 2 in the past have mostly focused on tedious probabilistic directed evolution approaches. Here we demonstrate that a rational approach combining multiscale MD simulations and Born-Oppenheimer ab initio QM/MM MD simulations is an efficient approach to rapidly identify improved enzyme variants. Thus, the lipase from Penicillium camembertii was redesigned with a single mutation (I260R), leading to drastic improvements in H 2 O 2 resistance while maintaining the catalytic activity. Also the extension of this methodology to other enzymes is demonstrated.
- Published
- 2019