Enzymes,
as nature’s catalysts, speed up the very reactions
that make life possible. Hydrolytic enzymes are a particularly important
enzyme class responsible for the catalytic breakdown of lipids, starches,
and proteins in nature, and they are displaying increasing industrial
relevance. While the unrivalled catalytic effect of enzymes continues
to be unmatched by synthetic systems, recent progress has been made
in the design of hydrolase-inspired catalysts by imitating and incorporating
specific features observed in native enzyme protein structures. The
development of such enzyme-inspired materials holds promise for more
robust and industrially relevant alternatives to enzymatic catalysis,
as well as deeper insights into the function of native enzymes. This
Review will explore recent research in the development of synthetic
catalysts based on the chemistry of hydrolytic enzymes. A focus on
the key aspects of hydrolytic enzyme structure and catalytic mechanism
will be exploredincluding active-site chemistry, tuning transition-state
interactions, and establishing reactive nanoenvironments conducive
to attracting, binding, and releasing target molecules. A key focus
is to highlight the progress toward an effective, versatile hydrolase-inspired
catalyst by incorporating the molecular design principles laid down
by nature.