Enzymes development

The detergent industry is the largest user of industrial enzymes. The starch industry, the first significant user of enzymes, developed special symps that could not be made by means of conventional chemical hydrolysis. These were the first products made entirely by enzymatic processes. Materials such as textiles and leather can be produced in a more rational way when using enzyme technology. Eoodstuffs and components of animal feed can be produced by enzymatic processes that require less energy, less equipment, or fewer chemicals compared with traditional techniques. 

It is apparent that the use of enzymatic catalysis continues to grow Greater availabiUty of enzymes, development of new methodologies for thek utilization, investigation of enzymatic behavior in nonconventional environments, and the design and synthesis of new biocatalysts with altered selectivity and increased stabiUty are essential for the successhil development of this field. As more is learned about selectivity of enzymes toward unnatural substrates, the choice of an enzyme for a particular transformation will become easier to predict. It should simplify a search for an appropriate catalyst and help to estabhsh biocatalytic procedures as a usehil supplement to classical organic synthesis. 

El Zoeiby A, Sanschagrin F, Levesque RC Structure and function of the Mur enzymes development of novel inhibitors. Mol Microbiol 2003, 47, 1-12. 

The following diagram, adapted from that first presented by Bennett et alC, describes a postulated pathway for evolution of a protein dimer from single-domain proteins. The scheme begins with the fusion of two singledomain polypeptides and proceeds through the evolution of interdomain contacts, and in the case of enzymes, development of an active site. These same interdomain contacts can also stabilize formation of a domain-swapped dimer which then undergoes further evolution into a present-day dimer. 

The placenta-derived enzyme was treated to make any associated risk of viral infections low, but a small risk of infection from human tissue remained, so scientists developed a recombinant replacement enzyme, with the right sugar embellishment, produced from a laboratory source. Unfortimately, about 15% of patients treated with the replacement enzyme develop antibodies to the protein that can reduce the usefulness of the injections and pose a risk of mild to severe allergic reactions. At the moment, however. 

Until recently, the use of enzymes in the paper and pulp industry was not cortsidered technically or economically feasible. Quite simply, suitable enzymes were not readily available, except for the limited use of enzymes to modify starch for paper coatings. However, research by scientific institutions and enzyme producers has led to the development of new enzymes that offer significant benefits for the industry, particrrlarly from the environmental point of view. Two examples of applications, in addition to the starch modification, made possible by new enzyme developments are given here bleach boosting and pitch control. 

Enzyme Development, USA Enzeco alkaline protease B. licheniformis industrial... 

Old and new enzymes developed by this mechanism are members of the same superfamily. The main champions of this mechanism are Gerlt and Babbitt (Gerlt, 1999 Babbitt, 2000). Readers are also encouraged to consult the reference on catalytic promiscuity by O Brien and Herschlag (O Brien, 1999). 

The catalytic strategy that an enzyme develops over evolutionary time is dictated by the chemistry of the reaction being catalyzed. The prolyl isomerases that have been studied to date are able to simply stabilize the nonenzymatic transition state without formation of covalent intermediates. Based on a value of lO" sec for CyP (Harrison and Stein, 1992 Kofron et ai, 1991) and a of sec" for the cis-to-trans isomerization of Suc-Ala-Ala-cis-Pro-Phe-pNA, we calculate an acceleration factor, of 10 , which corresponds to a transition state... 

Internal protein motion (H exchange) increases from 1/1000 at 0.04 A to full solution rate at 0.15 A At 0.1-0.15 A chymotrypsin and some other enzymes develop activity At 0.15 A long-range proton movements along percolative networks, seen in dielectric measurements... 

Another early example of polymorphism involves the drug succinylcholine (suxamethonium), a muscle relaxant used primarily during surgery. Its action lasts only a few minutes because it is very efficiently metabolized by cholinesterases present in the liver and plasma. A few people, about 1 in 3000 who genetically lack this enzyme, develop sustained apnoea as a result of paralysis because its effect is prolonged from 30 minutes to hours. 

The chemistry of model systems of hydrogenase enzymes has developed along with the study of the enzymes. Developments in the characterization of the enzyme have spurred the development of model systems that provide a better understanding of the function of the enzyme. Ultimately, a complete understanding of the chemistry of the hydrogenase enzymes will require the synthesis of both areas of study. In this review we consider the work that has been done to characterize the enzyme, focussing on the areas that are amenable for study using model systems. We then... 

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