Evolution of Enzyme Function

Koshland (1976) has considered the evolution of enzyme catalytic power from the point of view of the sequential acquisition of catalytic ability, specificity, regulability, and cooperativity. He contends that function is the driving force of evolution and must be subject to incremental improvements by small changes in structure, such incremental modifications occurring in a random manner. 

A primordial catalytic function could develop in a protein, perhaps by the chance juxtaposition of serine and histidine (imidazole) moieties. Improvements in the spatial arrangement can be made by random mutations of amino acids removed from the catalytic site. Similarly, improvements in binding-site orientation with respect to proximity of the substrate molecules to one another and to enzyme functional groups could occur by small degrees, which would then be fixed by selection. Thus, orientation and proximity, the crucial factors for binding interaction and entropic effects, are ideally suited for evolutionary optimization. 

Abramovitz, A. S., and Massey, V., 1976, Interaction of phenols with old yellow enzyme, /. Biol Chem. 251 5327. 

Albery, W. J., and Knowles, J. R., 1976, Evolution of enzyme fimction and the development of catalytic efficiency. Biochemistry 15 5631. 

---

Although the structure of haptens exerts an important influence on catalysis by antibodies, stabilization of the transition state by catalytic antibodies cannot always and cannot fully explain all observations. Sometimes, in analogy to the evolution of enzyme function, antibodies can take mechanistically unexpected detours. As an example, the corresponding antibody catalyzes the hydrolysis of arylamides according to Figure 18.3 by a factor of 2.5 x 105 over background. 

Yoshikuni Y, Ferrin TE, Keasling JD (2006) Designed divergent evolution of enzyme function. Nature 440 1078-1082... 

Yoshikuni Y, Eertin TE, Keasling JD (2006) Designed divergent evolution of enzyme function. Nature 440 1078-1082 Yu X-Z, Gu J-D (2009) Uptake, accumulation and metabolic response of ferticyanide in weeping willows. J Environ Monit 11 145-152... 

J.R. Knowles and W.J. Albery. 1976. Evolution of enzyme function and the development of catalyhc efficiency... 

Enzyme Mechanisms.— Triose phosphate isomerase has been a popular enzyme recently, having been the chief example quoted in two reviews on perfection and efficiency in enzyme catalysis - and the subject of seven successive papers in one issue of Biochemistry including one on the evolution of enzyme function and the development of catalytic efficiency. During glycolysis in muscle, fructose 1,6-bisphos-... 

Fruton, J. S. (1999). Proteins, Enzymes, Genes. New Haven, CT Yale University Press. Gerlt, J. A. and Babbit, P. C. (2001). Divergent evolution of enzymic function. Annual... 

Directed evolution of enzymes has been used to improve the reducing function of the enzymes. For example, this method was used to eliminate the cofactor requirement of B. stearothermophillus lactate dehydrogenase, which is activated in the presence of fructose 1,6-bisphosphate [12]. The activator is expensive and representative of the sort of cofactor complications that are undesirable in industrial processes. Three rounds of random mutagenesis and screening produced a mutant that is almost fully... 

Hall, B.G. (1981) Changes in the substrate specificities of an enzyme during directed evolution of new functions. 

Moore, J.C., Jin, H.M., Kuchner, O. and Arnold, F.H. (1997) Strategies for the in vitro evolution of protein function enzyme evolution by random recombination of improved... 

Horowitz NH. (t945). On the evolution of biochemical syntheses. Proceedings of the National Academy of Sciences, sr, 153-7. See also Jensen RA. (1976). Enzyme recruihnent in evolution of new function. Annual Review of Microbiology, 30, 409-425 Chapman DJ, Ragan MA. (1980). Evolution of biochemical pathways evidence from comparative hiochemistry. Annual Review of Plant Physiology, 31,639-78. 

Kuriyan,J., Krishna, T. S., Wong, L., Guenther, B., Pahler, A., Williams, C. H. Model, P. (1991). Convergent evolution of similar function in two structurally divergent enzymes. Nature, 352, 172-4. 

Verzhbinskaya, N.A. (1968). Biochemical evolution of enzyme systems as the base of functional evolution of vertebrate animals (In Russian). In Abiogenesis and Primary Stages of the Evolution of Life (A.I. Oparin ed.), pp.169-180, Nauka, Moscow. 

RA Jensen. Enzyme recruitment in evolution of new function. Annu Rev Microbiol 30 409-425, 1976. 

SHELLEY D. COPLEY is a professor of molecular, cellular and developmental biology at the University of Colorado at Boulder. Her research interests center on the molecular evolution of enzymes and metabolic pathways and protein structure-function relationships. Dr. Copley is a member of the Council of Fellows of the University of Colorado s Cooperative Institute for Research in Environmental Sciences. Dr. Copley served on the NSF Molecular Biochemistry Panel (1999-2003), was co-chair for the Gordon Conference on Enzymes, Coenzymes, and Metabolic Pathways (2004), and currently serves on the National Institutes of Health Genetic Variation and Evolution Study Section. 

Before the evolution of protein function can be studied, functional differences first must be demonstrated between members of the family. At present, the best comparative biochemical data exist for classically studied protein families, such as the globin family and several families of digestive enzymes.3... 

A common aim of directed evolution is to increase the stability of an enzyme to conditions of practical use that may be very different from those the enzyme naturally functions in. Factors such as heat, altered pH, and the presence of oxidants or organic solvents can lead to denaturation or loss of enzyme function. Many researchers have successfully increased the stability of an enzyme to thermal denaturation (41, 42). Work with p-nitrobenzyl esterase uicreased the melting temperature 14°C after six rounds of EP-PCR and recombination without forfeiting enzyme activity (41). As another example, phosphite dehydrogenase catalyzes the formation of phosphate from phosphite, by reducing NAD+ to NADH. However, the usefulness... 

D.E. Koshland Jr. 1987. Evolution of catalytic function Cold Spring Harbor Symp. Quant. Biol. 52 1-7. (PubMedl W.P. Jencks. 1987. Economics of enzyme catalysis Cold Spring Harbor Symp. Quant. Biol. 52 65-73. (PubMedl R.A. Lemer and A. Tramontane. 1988. Catalytic antibodies Sci. Am. 258 (3) 58-70. (PubMedl Books... 

In contrast to rational approaches, the directed evolution of enzymes is based on the search of useful functionalities in libraries randomly generated and on improvement by suitable and proper selection. The directed evolution combines two powerful and independent technologies methods for the generation of random genetic libraries and strategies for the selection of variant enzymes with the specific capabilities [499-503]. This process can result in biocatalysts with non-natural proprieties, since the proteins are expressed in recombinant cells decoupled from its biological functions and evolved under unusual conditions. One additional advantage is the possibility to tailor not only individual proteins, but also the whole biosynthetic and catabohc pathways [471]. 

---