Scientists have unlocked a new method for creating chemical reactions that breaks from the previously understood rules of enzyme engineering. This could open up a wide range of new applications, from creating drugs to methods of food production.
In a paper published by Nature Catalysis, Professor Francesca Paradisi and Dr Martina Contente of the University of Nottingham and the University of Bern show a new method to produce chemical molecules more efficiently through a new one step reaction in the enzyme.
“We have demonstrated how a very simple mutation in one of the key residues of a useful enzyme has dramatically expanded its synthetic scope, enabling the use of the mutant variant in the preparation of challenging chemical molecules, as well as natural metabolites that are vital in many biological processes in the body,” said Professor Paradisi.
Typically, in enzyme engineering, catalytic amino acids are highly conserved. Variations do sometimes occur, if the replacing amino acid is similar, both can be found in significant proportion in Nature, but others can be much less common and are found only in a limited number of species.
The study investigated a previously unexplored area of enzyme engineering and was able to modify a key catalytic residue in the active site of an enzyme.
Traditionally, the approach to changing the substrate scope of an enzyme has been to mutate the residues involved in substrate recognition, whether through rational design or directed evolution, always leaving the catalytic ones untouched.
Professor Paradisi commented: “Previously it was thought that doing this would cause a loss of activity of the enzyme but we have found this is not the case when this biocatalyst is used in a synthetic direction and in fact challenging but very useful molecules can now be made under mild conditions which could be easily scaled up and replicated commercially for use in a wide range of products.”
Dr Contente added: “We have had fantastic feedback on this study from the scientific community as it is providing a new tool for chemistry that can be applied to a wide range of molecular reactions. The fact that it is a very stable reaction created without the need for specific conditions mean it has the potential for a low-cost commercial application in the production of new pharmaceuticals. We believe we have unlocked a new combination in the catalytic triads which Nature seems to have disfavoured, possibly to tighten the control on reactivity, but that for a chemist could be a real goldmine.”