How To Break the Janus Effect of H 2 O 2 in Biocatalysis? Understanding Inactivation Mechanisms To Generate more Robust Enzymes
Ze Xin Zhao (South China University of Technology)
Dongming Lan (South China University of Technology)
Xiyu Tan (South China University of Technology)
Frank Hollmann (TU Delft - BT/Biocatalysis)
Uwe T. Bornscheuer (Greifswald University)
Bo Yang (South China University of Technology)
Yonghua Wang (South China University of Technology)
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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.