New technology to stabilize enzymes

VU researchers Marta Pelay-Gimeno, Sven Hennig and Professor Tom Grossmann (AIMMS) publish their new method to stabilize enzymes to increase their tolerance towards thermal and chemical stress in the scientific journal Angewandte Chemie.

08/06/2018 | 2:54 PM

Enzymes can perform chemical reactions very specifically in a highly efficient and environmentally friendly manner. It may take months to chemically synthesize a compound for which an enzyme only needs seconds.

Therefore, scientists have been trying to expand the repertoire of enzymes that can be used to produce compounds which are of industrial interest, and a breakthrough in this area would have a great socio-economic impact. However, many biotechnological applications involving enzymes require harsher and altered reaction conditions, especially when applied at larger industrial scales.

Molecular clamps
In their recent publication in Angewandte Chemie International Edition, Pelay-Gimeno and colleagues describe a technology to increase the robustness of enzymes for such applications. They do this by enforcing enzyme integrity with small molecular clamps which are attached to the enzyme’s surface. This clamp prevents the enzyme from disintegration under environmental stress, such as elevated temperatures.

The researchers show that a thus stabilized version of the enzyme sortase A, for example, has increased tolerance towards thermal and chemical stress and retains enzymatic activity under conditions it usually does not perform at. The new enzyme stabilization technology, termed in situ cyclization of proteins (INCYPRO), provides access to stabilized enzymes and proteins. INCYPRO will thus lead to more sustainable enzymatic applications, which has implications for a number of industrially relevant processes, such as the synthesis of small-molecule drugs in the pharmaceutical industry or synthesis of raw materials for the plastic industry.

Grossmann-et-al-in-Angewandte-Chemie
Picture: The graphic shows the enzyme (grey) at higher temperatures (fire ball). With the small molecular clamp (red) attached, the enzyme keeps its integrity (3D structure) and is more resistant to the elevated temperatures.