A Bird’s-Eye View of Enzyme Evolution: Chemical, Physicochemical, and Physiological Considerations

Enzymes
catalyze a vast range of reactions. Their catalytic performances,
mechanisms, global folds, and active-site architectures are also highly
diverse, suggesting that enzymes are shaped by an entire range of
physiological demands and evolutionary constraints, as well as by
chemical and physicochemical constraints. We have attempted to identify
signatures of these shaping demands and constraints. To this end,
we describe a bird’s-eye view of the enzyme space from two
angles: evolution and chemistry. We examine various chemical reaction
parameters that may have shaped the catalytic performances and active-site
architectures of enzymes. We test and weigh these considerations against
physiological and evolutionary factors. Although the catalytic properties
of the “average” enzyme correlate with cellular metabolic
demands and enzyme expression levels, at the level of individual enzymes,
a multitude of physiological demands and constraints, combined with
the coincidental nature of evolutionary processes, result in a complex
picture. Indeed, neither reaction type (a chemical constraint) nor
evolutionary origin alone can explain enzyme rates. Nevertheless,
chemical constraints are apparent in the convergence of active-site
architectures in independently evolved enzymes, although significant
variations within an architecture are common.