Enzymes are generally in a state that is not only a compromise between stability and catalytic efficiency, but also for specificity and evolvability, the latter two dictating whether an enzyme is a generalist (highly evolvable due to large promiscuity, but low main activity) or a specialist (high main activity, poorly evolvable due to low promiscuity). Examples of these are enzymes for primary and secondary metabolism in plants (§
Plant secondary metabolism below). Other factors can come into play, for example the glycerophosphodiesterase (
gpdQ) from
Enterobacter aerogenes shows different values for its promiscuous activities depending on the two metal ions it binds, which is dictated by ion availability. In some cases promiscuity can be increased by relaxing the specificity of the active site by enlarging it with a single mutation as was the case of a D297G mutant of the
E. coli L-Ala-D/L-Glu epimerase (
ycjG) and E323G mutant of a pseudomonad muconate lactonizing enzyme II, allowing them to promiscuously catalyse the activity of O-succinylbenzoate synthase (
menC). Conversely, promiscuity can be decreased as was the case of γ-humulene synthase (a sesquiterpene synthase) from
Abies grandis that is known to produce 52 different sesquiterpenes from farnesyl diphosphate upon several mutations. Studies on enzymes with broad-specificity—not promiscuous, but conceptually close—such as mammalian trypsin and chymotrypsin, and the bifunctional isopropylmalate isomerase/homoaconitase from
Pyrococcus horikoshii have revealed that active site loop mobility contributes substantially to the catalytic elasticity of the enzyme.
Toxicity A promiscuous activity is a non-native activity the enzyme did not evolve to do, but arises due to an accommodating conformation of the active site. However, the main activity of the enzyme is a result not only of selection towards a high catalytic rate towards a particular substrate to produce a particular product, but also to avoid the production of toxic or unnecessary products. Similar in reaction to tRNA synthesis, the first subunit of tyrocidine synthetase (
tyrA) from
Bacillus brevis adenylates a molecule of phenylalanine in order to use the adenyl moiety as a handle to produce
tyrocidine, a cyclic
non-ribosomal peptide. When the specificity of enzyme was probed, it was found that it was highly selective against natural amino acids that were not phenylalanine, but was much more tolerant towards unnatural amino acids. Specifically, most amino acids were not catalysed, whereas the next most catalysed native amino acid was the structurally similar tyrosine, but at a thousandth as much as phenylalanine, whereas several
unnatural amino acids where catalysed better than tyrosine, namely D-phenylalanine, β-cyclohexyl-L-alanine, 4-amino-L-phenylalanine and L-norleucine.
Plant secondary metabolism (
delphinidin pictured) confer plants, particularly their flowers, with a variety of colours to attract pollinators and a typical example of plant secondary metabolite. 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. ==Biocatalysis==