Enzymatic Engineering | Research & Encyclopedia Articles

Enzymatic Engineering

An enzyme is a protein which accelerates, or (catalyzes), the chemical reactions of living cells. Most biochemical reactions would be too slow to support life without enzymes. Enzymes can be manipulated through the science of enzymatic engineering which alters existing natural substances or builds new ones from natural or artificial materials. Enzyme research and enzymatic engineering include methods and concepts from protein chemistry, molecular biophysics, and molecular biology.

The term enzyme, coined in the late nineteenth century, means leavening and people have recognized the importance of enzyme activity for thousands of years. One of the earliest and most well known of all enzyme-catalyzed reactions is the fermentation of sugar to alcohol. The first enzyme to be isolated was diastase, which catalyzes the hydrolysis of starches into sugars, in 1833. It was also the first enzyme to be patented, in 1894 by Jokichi Takemine (1854-1922). Pepsin, an important enzyme in the digestive process, was identified in 1839 through efforts by many scientists, including those of the American William Beaumont (1785-1853). The isolation of pepsin in 1930 proved that enzymes are proteins. The first enzymatic engineering also began in the 1930s, when scientists modified pepsin and other enzymes by removing or replacing groups. Since that time six classes of enzymes have been identified: oxidoreductasescarry out redox (electron transfer) reactions; transferases transfer a group (such as a phosphate) from one substance to another; hydrolases break bonds by hydrolysis, such as carbon-oxygen or carbon-carbon; lyases break bonds by elimination; isomerases rearrange molecules structurally; and ligases join molecules, along with hydrolysis of a triphosphate bond.

All these abilities are being used in modern enzymatic engineering, which began in the late 1950s by such pioneers as the three winners of the 1987 Nobel prize for chemistry-- Donald J. Cram (1919-), of the University of California, Los Angeles; Jean-Marie Lehm (1939-), of Louis Pasteur University (Strasbourg) and College de France (Paris); and Charles Pederson (1904-), now retired from E.I. duPont de Nemours & Co. Their work involved discovering the structure and function of enzymes, and attempting to create synthetic counterparts of the enzymes, their receptors (called hosts), and substrates, inhibitors, or cofactors (guests). Enzymes are now used in science and medicine for cancer therapy, treatment of wounds, and genetic engineering. They are also part of chemical production, pulp and paper processing, and municipal solid waste disposal. Other industrial uses include production of detergents, leather, and fuel alcohol, as well as manufacturing of syrups and sweeteners, starch processing and baking, meat processing, cheesemaking, and wine production.

Enzyme engineers work to adapt or mimic or adapt these processes in several ways. An existing enzyme can be modified by amino acid substitution, without disturbing the structure, for instance, so it will work at high temperatures instead of body temperature. An enzyme can be combined with other substances to carry out a reaction. Scientists at Rockefeller University have combined the enzyme papain, which breaks down proteins (it is used as a meat tenderizer), with nitrogen compounds called flavins. The resulting compound is more versatile. Substances can also be engineered to work like enzymes. Scientists at California Institute of Technology have combined an oxygen-binding protein called myoglobin with the metal ruthenium, which can start chemical reactions. The resulting enzyme can carry oxygen to a site, then perform an oxidation reaction. Genetic engineering techniques can be used to change the genes, adding, deleting, or substituting DNA nucleotides. Once these changes are made, the cell assembles different amino acids, making a new enzyme. Mutations are being studied by many scientists for use in medical treatment and industry. For example, research in 1997 have revealed how the enzyme human topoisomerase I removes the additional twists that accumulate in DNA. This research suggests a new mechanism for enzyme functionality.