When it comes to sugars, most people want to find ways to break them down. But there are a few scientists who want to figure out ways to put these compounds together. Recently, researchers took this desire to the extreme by devising machines that synthesize sugars.1 The work represents an important milestone for scientists studying sugar biochemistry. It also provides new reasons to believe that life emanates from the work of a Creator.
Sugars belong to a class of biomolecules called carbohydrates. This class of compounds consists of carbon, hydrogen, and oxygen in the specific ratio of 1:2:1, respectively. (Biochemists use the general formula CnH2nOn, [where n can be any number] to represent carbohydrates.)
Carbohydrates (also called saccharides) come in a variety of forms. Monosaccharides (mono = one) are carbohydrates composed of a single sugar residue. Glucose and fructose are two monosaccharides recognizable to the diet-conscious. Disaccharides (di = two) consist of two sugars linked together. One familiar example of a disaccharide is sucrose (table sugar), which consists of the sugars glucose and fructose linked together.
Polysaccharides (poly = many) form when numerous sugars link together. Starch and cellulose are two common examples of polysaccharides, both consist of glucose linked together in long chains. The difference between starch and cellulose stems from the nature of the linkage between the individual glucose molecules.
Oligosaccharides (oligo = few) form when a handful of sugar molecules are linked together. Frequently, oligosaccharides are attached to proteins associated with the exterior surface of cell membranes and proteins secreted by the cell. These oligosaccharides play a structural role, for example, mediating cell-cell contact. In spite of these compounds’ importance, biochemists have limited understanding of the structure-function relationships for oligosaccharides. One of the reasons for this lack of insight is the short supply of pure, chemically defined oligosaccharides. These compounds are found at such low concentrations in nature that purifying them from a biological source is often not a realistic option.
Laboratory Synthesis of Sugars
Synthesizing the desired oligosaccharide in the lab represents one sure way around this dilemma. But this is not a trivial task, by any means. Part of the problem is that when sugar molecules react, they can combine in a number of different ways. For example, fructose and glucose can, in principle, form 50 different bonds with each other, only one of which makes the disaccharide sucrose.
One trick chemists use to control the specificity of the reaction between sugars is to attach protecting groups to reactive parts of the molecule. These groups prevent the reactive moieties from participating in chemical reactions. Researchers have devised techniques that allow them to remove specific protecting groups selectively. By judiciously choosing which protecting groups to remove, chemists can precisely control the types of bonds that form between two sugars, directing them to combine in only one possible way.
Because sugars have so many reactive groups, it is very difficult to employ the above strategy to synthesize a desired oligosaccharide. In fact, only a few laboratories around the world have the capability to carry out the synthesis of these types of carbohydrates.
To address this problem, some scientists are trying to build machines that will carry out the automated synthesis of oligosaccharides. These machines will make it possible for researchers working on oligosaccharide biochemistry to make structurally defined sugars quickly and inexpensively without relying on the skills of highly specialized chemists.
Significant strides have been made towards this end. A few months ago, two separate groups unveiled commercially available oligosaccharide-synthesizing machines. German chemist Peter Seeberger heads up one group. He based his machine on a sophisticated chemical protocol he developed and published nearly a decade ago.2 At that time, many people felt the chemistry was too complicated and unreliable for use in an automated sugar synthesizer. So Seeberger spent the last decade perfecting the chemistry and the automated synthesizer. It’s now at the point where a nonexpert can run the machine and carry out a task that once took a team of accomplished chemists to achieve.
This advance was decades in the making. Moreover, Seeberger based the chemistry for his automated sugar synthesizer on the techniques employed by automated DNA synthesizers and peptide synthesizers—techniques that were awarded the Nobel Prize in Chemistry. (Bruce Merrifield, for example, received the prize in 1984 for his work in solid-phase peptide synthesis.)
The difficulty in making oligosaccharides in the lab, either by conventional methods at the bench top or within the internal operations of a sugar synthesizer, stands in sharp contrast to the elegant and effortless way living systems produce these compounds via metabolic pathways mediated by enzymes. The structure of the enzymes makes it possible for sugar units to be combined to make oligosaccharides in a highly specific manner inside the cell. This process takes just a few short steps without the need for adding and then selectively removing protecting groups.
This contrast between manmade and natural systems forces the question: given the difficulty the best chemists in the world (who stand on the shoulders of generations of scientists before them) experience in assembling even relatively small oligosaccharides, is it reasonable to conclude that the elegant and highly efficient metabolic systems inside the cell arose by undirected evolutionary processes? It seems more rational to conclude that the biochemical systems inside the cell are the work of an intelligent Agent who carefully devised the structures and operations of enzymes to carry out what otherwise would be nearly impossible chemical syntheses.