Researchers managed for the first time ever to 'retrain' an enzyme to build ring-shaped molecular structures instead of performing its natural task of reducing double bonds. The work is relevant for the production of pharmaceuticals and plant protection products.

Biocatalysis uses enzymes to bring about chemical reactions. This kind of 'soft chemistry' replaces the use of poisonous reagents or solvents in existing syntheses to a high degree. However, a major challenge in biocatalysis is extending this concept to completely novel chemical reactions so far not accessible to enzymes found in nature.

Molecular Structure Of Enzyme

'For the first time, they have succeeded in manipulating an enzyme to carry out not its natural function, but rather a much more interesting function regarding synthesis. Instead of reducing double bonds in a catalytic process, the enzyme now creates molecular structures in the form of small rings. By exchanging only one amino acid in the active center of the enzyme, we've managed to suppress the natural reaction and facilitated a new reaction course.'

They can produce 'cyclopropanes' extremely small ring-shaped molecules in the shape of a triangle using biocatalysis. Such ring systems, also called three-ring systems, occur not only in many biomolecules, they are also an important structural element in plant protection products and in pharmaceuticals such as contraceptive pills, drugs used to treat asthma and AIDS medications. 

The good and the bad 'hand' of the molecule

Parallel to this, the researchers also managed to master the chirality of the produced molecule, which is of great importance in the production of medications. Chirality, or the 'handedness' of molecules, describes how two molecules of the same atom can be structured in a mirror-image way either right handed or left handed.

Enantiomers

One variant of these enantiomers can be useful and the other damaging, and great value is placed today on using only the curative variant in the production of medications. This ensures that medications work very specifically and that no undesirable side effects occur due to 'chiral twins'.

To enable an optimum chiral recognition between enzyme and substrate, we designed a substrate with a large residue. By doing this, we could ideally exploit the spatial conditions in the active center of the enzyme to produce a cyclopropane in high enantiomeric purity.

TU Graz as an international center of biocatalysis research 

The research team from TU Graz managed to carry out an important extension of their biocatalytic repertoire to open the door to diverse applications particularly in the 'green' production of new medications and the economical production of generic pharmaceuticals, aromatic substances, and plant protection products. 

The aim of this so-called green chemistry, to which biocatalysis can be attributed, is to employ mild and environmentally sound reagents, contain environmental pollution, and save energy and costs.