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Promiscuous activity


Enzyme promiscuity is the ability of an enzyme to catalyse a fortuitous side reaction in addition to its main reaction. Although enzymes are remarkably specific catalysts, they can often perform side reactions in addition to their main, native catalytic activity. These promiscuous activities are usually slow relative to the main activity and are under neutral selection. Despite ordinarily being physiologically irrelevant, under new selective pressures these activities may confer a fitness benefit therefore prompting the evolution of the formerly promiscuous activity to become the new main activity. An example of this is the atrazine chlorohydrolase (atzA encoded) from Pseudomonas sp. ADP which evolved from melamine deaminase (triA encoded), which has very small promiscuous activity towards atrazine, a man-made chemical.

Enzymes are evolved to catalyse a particular reaction on a particular substrate with a high catalytic efficiency (kcat/KM, cf. Michaelis–Menten kinetics). However, in addition to this main activity, they possess other activities that are generally several orders of magnitude lower, and that are not a result of evolutionary selection and therefore do not partake in the physiology of the organism. This phenomenon allows new functions to be gained as the promiscuous activity could confer a fitness benefit under a new selective pressure leading to its duplication and selection as a new main activity.

Several theoretical models exist to predict the order of duplication and specialisation events, but the actual process is more intertwined and fuzzy (§ Reconstructed enzymes below). On one hand, gene amplification results in an increase in enzyme concentration, and potentially freedom from a restrictive regulation, therefore increasing the reaction rate (v) of the promiscuous activity of the enzyme making its effects more pronounced physiologically ("gene dosage effect"). On the other, enzymes may evolve an increased secondary activity with little loss to the primary activity ("robustness") with little adaptive conflict (§ Robustness and plasticity below).


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