Elucidating the role of conformational dynamics of Aspergillus niger Monoamine oxidase towards enzymatic chiral amines synthesis

Enzymes have evolved through years until becoming great catalysts that present high selectivity, specificity, and activity. Initially, enzymes were understood as static (bio)molecular structures capable of accelerating chemical reactions by many orders of magnitude. Notwithstanding, after decades of research, they could be identified as dynamic entities, able to adopt different thermally accessible conformations key for their catalytic function. The advantages that enzymes present when it comes to increase the reaction rate of (bio)chemical reactions can be used for producing industrially relevant compounds. In this regard, enzymes present a limitation, in most cases they are not active enough towards non-natural reactions or substrates relevant for industrial purposes. Such limitation can be overcome by means of enzyme engineering, which consists of introducing mutations in the enzyme sequence either using computational or experimental protocols. Experimentally, one of the most used techniques is Directed Evolution (DE), that performs random mutations along the enzyme sequence, producing variants with several fold increase in activity or selectivity of the targeted reaction. However, DE is based on the generation of thousands of variants which result in a time-consuming process, without any knowledge on how the enzyme structural and dynamic properties have been modified. In this context, there is a need for more rational techniques that could be used to generate new enzyme variants with improved activity and broader substrate scope using less resources ​
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