The role of Enzymes, as catalysts

Given the power of modern molecular biology we can use gene transfer to essentially make a cell do whatever we want it to do. We can play God in that cell.

Richard Mulligan

If a biologist were to be asked to name what, in his opinion, is the most wonderful product of evolution, and given a broad spectrum that includes the eye of the condor, the tail of the peacock, the gigantic California Redwood tree, the dolphin, which has the remarkable ability to communicate in the ocean depths, and the various animal species in the Galapagos with their unique survival skills, he would brush them all aside stating that no single animal, plant or sensitive organ can qualify for the honour. Indeed, his choice would most probably fall on enzymes, the marvellous catalysts of cell chemistry that mould, fashion and sustain the whole rich carpet of life on Earth. These exquisitely precise agents are responsible for every one of the countless chemical transformations that take place inside all living cells and they work with an economy that even no big chemical industry can rival.

The question arises as to why plants and animals, e.g. cabbages, butterflies, buffaloes, are quietly and efficiently able to conduct reactions that would require high temperatures, powerful pressures and poisonous metal catalysts. Until a few years ago, scientists had only the haziest notion of an answer, but now molecular biologists are seriously discussing the prospects of manufacturing enzymes similar to those inside our own cells but of a much better quality.

Since it has been estimated that in the United States alone there is an annual market for industrial enzymes worth about USD 150 million, the introduction of totally synthetic types can be expected to bring incalculably high rewards.

There are many motives for creating new enzymes. One is, of course, to enhance the effectiveness of their natural counterparts and thereby, the rate of chemical conversions. Another is to alter their structure to render them more stable. For instance, heat-resistant enzymes could be of great value in high temperature industrial reactions.

One might be tempted to ask as to how scientists go about building a better enzyme? Like all industrial pirates, they begin by scrutinising the competitor’s product—in this case, nature’s own catalysts. The enzymes contained within living cells are proteins consisting of long chains of various amino acids. (The constituent elements of proteins are carbon, hydrogen, oxygen, nitrogen along with usually sulphur and very often phosphorous.) These elements are combined to form the basic building blocks of any protein—the units known as amino acids. Amino acids link together to form proteins. When two amino acids join, they form a unit called a dipeptide; further amino acids units join forming a larger complex, known as a polypeptide. Polypeptides are long chains of amino acids and proteins are formed when adjacent polypeptide chains cross-link with each other. Proteins are used for the synthesis and repair of cells and hence are essential for healthy life and growth. They also provide the raw materials for the synthesis of enzymes. Each protein has a distinctive sequence. Such a sequence and the way the molecule is folded into its three- dimensional shape are what account for its unique activity; one enzyme promotes one particular reaction only. Such remarkable specificity is encoded in the lengthy sequence of amino acids; in fact, about 150 are strung together in an average sized enzyme.

The task of constructing an organic product from these sequences is a painstaking one. It is far better to imitate not only nature’s prod­ucts but also its way of fabricating them. Like other proteins, every enzyme is made according to a corresponding DNA template. The vital question is: can the new science of genetic engineering be usefully employed in this connection? What we require, as genetic engineers have noted, is the ability to read, write and edit in the language of DNA. If these objectives can be achieved, we will have an elegant route for synthesising even complex proteins.

Reading is no longer a problem. About three decades ago, Nobel Prize winner Dr Fred Sanger of England’s prestigious Cambridge University first described the techniques for spelling out all the words in a piece of coded DNA. Since then a spurt in scientific activity has appeared with several strategies for fabricating recombinant DNA. With the recent arrival of ‘gene machines’ ,writing is fast becoming an automated process. Scientists expect that in the future it should be possible to type out an enzyme amino acid sequence at one end and get readymade DNA at the other. They are now busy trying to perfect methods for editing this genetic material which entails transferring it to a bacterial host that will mass-produce the specified enzyme. Genetic engineers predict that genetic synthesis will be commonplace very soon.

So, the way ahead is clear. Scientists would be justified in conceiving of enzymes, which would be much more industrious than those now in existence. Genetic engineers may even create enzymes capable of promoting reactions that neither man nor nature has ever contemplated. The market for industrial enzymes is steadily rising and is expected to reach higher figures than the present conservative estimates of about USD 100 million annually once the craft of enzymes design is mastered.

Our age has witnessed spectacular advances in several branches of medical science and technology. Just as organ transplants have revo­lutionised surgery, the manufacture of enzymes.