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