Enzyme promiscuity
Although enzymes are remarkably specific catalysts, they can often perform side reactions in addition to their main, native catalytic activity.
ADP evolved from melamine deaminase (triA encoded), which has very small promiscuous activity toward atrazine, a man-made chemical.
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).
Due to the very low number of amino acid changes, these provide an excellent model to investigate enzyme evolution in nature.
One study showed that the ancestral gene of the immune defence protease family in mammals had a broader specificity and a higher catalytic efficiency than the contemporary family of paralogues,[10] whereas another study showed that the ancestral steroid receptor of vertebrates was an oestrogen receptor with slight substrate ambiguity for other hormones—indicating that these probably were not synthesised at the time.
The mechanisms by which the noncognate ORF could rescue the knockout can be grouped into eight categories: isozyme overexpression (homologues), substrate ambiguity, transport ambiguity (scavenging), catalytic promiscuity, metabolic flux maintenance (including overexpression of the large component of a synthase in the absence of the amine transferase subunit), pathway bypass, regulatory effects and unknown mechanisms.
[18] This crosswise promiscuity has been most studied with members of the alkaline phosphatase superfamily, which catalyse hydrolytic reaction on the sulfate, phosphonate, monophosphate, diphosphate or triphosphate ester bond of several compounds.
[28] Plants produce a large number of secondary metabolites thanks to enzymes that, unlike those involved in primary metabolism, are less catalytically efficient but have a larger mechanistic elasticity (reaction types) and broader specificities.
The liberal drift threshold (caused by the low selective pressure due to the small population size) allows the fitness gain endowed by one of the products to maintain the other activities even though they may be physiologically useless.
To do this, enzymes with a small promiscuous activity towards the required reaction are identified and evolved via directed evolution or rational design.
[30] An example of a commonly evolved enzyme is ω-transaminase which can replace a ketone with a chiral amine[31] and consequently libraries of different homologues are commercially available for rapid biomining (eg.
Another example is the possibility of using the promiscuous activities of cysteine synthase (cysM) towards nucleophiles to produce non-proteinogenic amino acids.
