A Research Study On Catalytic Promiscuity And The Emergence Of New Enzymes
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Catalytic promiscuity provides a starting point for the evolution of new enzymes. When a secondary “promiscuous” activity becomes physiologically relevant, selection will favor genetic changes that improve upon this promiscuous activity. When the ability to do both activities limits growth, it is called an “Inefficient” bi-functional enzyme. The Copley lab at the University of Colorado at Boulder has found several genetic changes that increase fitness in a ΔargC strain of Escherichia coli BW25113 when growth is limited by an inefficient bi-functional enzyme (ProA*). The experiments described in this thesis investigate the genetic changes that increase fitness in a ΔargC strain of Salmonella enterica serovar Typhimurium str. SL1344 when…show more content… In most cases, gene duplications are expected to be either selectively neutral or detrimental due to the fitness costs of their maintenance, limiting the ability of a cell to maintain duplicated copies long enough for beneficial mutations to occur (13). However, solutions to this problem have been proposed based on the observation that most new enzyme activities closely resemble the original activity of the enzyme.
Active sites of specialized enzymes often bind molecules that have some resemblance to their natural or physiological substrates, although usually with much lower affinity (16). If an enzyme can bind an unintended substrate and catalyze a secondary reaction that is physiologically irrelevant, it is said to have “catalytic promiscuity”. If this secondary activity becomes physiologically relevant by increasing fitness, selection will favor genetic changes that take advantage of this new activity (11). The promiscuous activity of essential enzymes or those that are constitutively expressed are usually the first to be recruited in the face of an environmental change due to their active and selectable presence in the cell (11). Alternatively, mutations that cause constitutive expression of non-essential genes that can be subsequently recruited to produce essential metabolites via their promiscuous activities have been documented (29, 5). In either case,