Enzymes function, evolution

In principle, numerous reports have detailed the possibility to modify an enzyme to carry out a different type of reaction than that of its attributed function, and the possibility to modify the cofactor of the enzyme has been well explored [8,10]. Recently, the possibility to directly observe reactions, normally not catalyzed by an enzyme when choosing a modified substrate, has been reported under the concept of catalytic promiscuity [9], a phenomenon that is believed to be involved in the appearance of new enzyme functions during the course of evolution [23]. A recent example of catalytic promiscuity of possible interest for novel biotransformations concerns the discovery that mutation of the nucleophilic serine residue in the active site of Candida antarctica lipase B produces a mutant (SerlOSAla) capable of efficiently catalyzing the Michael addition of acetyl acetone to methyl vinyl ketone [24]. The oxyanion hole is believed to be complex and activate the carbonyl group of the electrophile, while the histidine nucleophile takes care of generating the acetyl acetonate anion by deprotonation of the carbon (Figure 3.5). 

Eggert, T., Jaeger, K.-E. and Reetz, M.T. (2004) Directed evolution of random mutagenesis a critical evaluation, in Enzyme Functionality (ed. A. Svendsen), Marcel Dekker, Inc., New York, pp. 375-390. 

Sen, S., Venkata Dasu, V. and Mandal, B. (2007) Developments in directed evolution for improving enzyme functions. Applied Biochemistry and Biotechnology, 143, 212-223. 

MARSOLAIS, F GIDDA, S.K., BOYD, J., VARIN, L Plant soluble sulfotransferases structural and functional similarity with mammalian enzymes. In Evolution of Metabolic Pathways (J.T. Romeo, R. Ibrahim, L. Varin, V. de Luca, eds.), Elsevier Science Ltd., Amsterdam. 2000, pp. 433-456. 

Albery, W.J. and Knowles, J.R. (1976) Evolution of enzyme function and the development of catalytic efficiency. Biochem., 15, 5631-5640. 

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. 

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. 

WK Yeh, SK Ghag, SW Queener. Enzymes for epimerization of isopenicillin N, ring expansion of penicillin N, and 3 -hydroxylation of deacetoxycephalosporin C function, evolution, refolding, and enzyme engineering. Ann NY Acad Sci 672 396-408, 1992. 

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... 

Directed evolution has been successfully used to alter existing enzyme properties and even to create novel enzyme functions. In addition to creating enzymes for specific industrial applications, directed evolution has also been increasingly used to address fundamental questions in biology, such as the evolutionary mechanisms of novel protein functions, protein structure-function relationship, and protein folding mecha-... 

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... 

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-... 

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