Researchers prove custom-designed enzymes are possible
custom-designed for a new and pre-determined activity, signalling a
new direction in drug production as well as having relevance to the
biotechnological and medicinal industry.
"The product in this case is not the main point, but we have shown that it is possible to totally transform an enzyme," said Professor Bengt Mannervik, at the Department of Biochemistry and Organic Chemistry, who planned the study.
"We have succeeded by using a rational reconstruction of the enzyme's active site in combination with directed molecular evolution in test tubes."
Bengt Mannervik and his research team at Uppsala University, in collaboration with Hak-Sun Kim's research team in Korea, have converted an enzyme in human cells that participates in normal metabolism into an enzyme that degrades cefotaxime, an antibiotic similar to penicillin.
The human enzyme was complemented with parts from the bacterial enzyme beta-lactamase, which bacteria use to break down antibiotics of the penicillin type.
The scientists then managed to isolate bacteria with the new enzyme and to show that they enhanced their capacity to survive by degrading cefotaxime.
"The study shows that it is possible to drastically alter the properties of a natural protein and that an enzyme's functions can be custom-designed for new uses," said Bengt Mannervik.
The researchers, stated however, that they had to look for proteins at random after reconstructions, like a needle in a haystack.
In the cells of all organisms, proteins are involved in molecular functions of highly disparate types: as receptors of light and smells, for transmission of signals, mechanical work, control of the function of genes, and the synthesis and degradation of chemical substances.
Despite all of these diverse functions, only a small number of all protein structures ever come to existence in living cells.
Custom-made enzymes have already been used extensively in such sectors as the forestry and agriculture, and the production of foodstuffs, to great effect. What the scientists have discovered in this latest study is set aid drug discovery and research tenfold.
With the microbial Catalase from Corynebacterium glutamicum Roche Applied Sicence has been developed especially for highly regulated applications, e.g. medical devices such as contact lens cleaning systems.
Here, Catalse helps to remove the eye-irritating substance hydrogen peroxide, which is required during the cleaning process.
Catalase converts hydrogen peroxide into water and oxygen and can be used wherever hydrogen peroxide needs to be removed, be it an active component or an intermediate product in an industrial process.