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Chemist Wolfgang Kroutil is researching methods that enable the simple and inexpensive manufacture of medicines. To do this, he uses a form of biocatalysis which is also environmentally friendly.

The high cost of medicines can often make therapies quite unaffordable. This has serious consequences for the poorest members of society. Behind the high costs are complex production processes. “On average, between five to fifteen steps are necessary in order to manufacture a drug,” explains Kroutil, who is conducting research at the Institute of Chemistry, part of the University of Graz, Austria. This entails a high level of energy consumption as well as expensive processes for the pharmaceutical industry. Kroutil identifies the relevant cost factors in conventional organic chemistry processes below:

  • Generation of environmentally harmful waste that is costly and time-consuming to dispose of;
  • Chemical reactions which require temperatures as low as minus ninety degrees Celsius and can only be induced by using expensive cooling processes and chemical solvents;


Optimizing chemical reactions

Biocatalysis is a relatively new approach within organic chemistry which makes it possible to induce cleaner and more energy-efficient chemical reactions. This branch of research first originated in Graz in the 1990s. For many years, Kroutil has been researching biocatalysis as well – with a view to making it useful in the medical field. Sitagliptin has been successfully in use since 2005 in the treatment of type II diabetes mellitus. It is a drug that he has been actively involved with the research and development of.  As Kroutil explains, it is rather unusual in the pharmaceutical industry to replace established processes with new ones. However, the replacement of chemical reactions by biocatalysis in the manufacture of sitagliptin caused the industry to sit up and take notice. And this led to a rethink.

Holistic approach

Biocatalysis enables various ways to modify molecules and develop new methods. Ways that industry has been using to redefine a variety of chemical reactions ever since. To date, however, the use of biocatalysis is still comparable to the bit-by-bit renovation of a house. Kroutil: “Sitagliptin involves the animation of ketones. This is comparable to replacing a window. Nowadays, other elements such as doors and roofs can also be replaced. But we are working on rebuilding the house from scratch.” The researcher and his team are looking for a method for redesigning the structure of organic molecules using enzymes.


Biokatalyse als umweltfreundliche Art der Herstellung von Medikamenten
Wolfgang Kroutil (c) Uni Graz – Kanizaj


Nature as a model

Biocatalysis helps reduce the use of chemicals and greatly simplifies and accelerates the manufacture of medicines. Kroutil talks about a pharmaceutical company which has succeeded in reducing the production steps from fifteen chemical reactions to three biocatalyses. On top of that, expensive cooling processes and chemical solvents from conventional manufacturing processes are avoided. The researchers are guided by nature, where catalysts do not need minus degrees. Instead they function at temperatures of twenty to forty degrees Celsius. Unlike catalysts in organic chemistry up until now, catalysts in nature are focused on one substance and convert it exclusively into a specific product.

Enzymes from renewable raw materials

Enzymes from nature take over complex chemical reactions in the biocatalysis process – and have the effect of accelerating them. The microorganisms necessary for this are produced from renewable proteins. In contrast to waste materials from conventional production processes, biocatalysis waste materials are able to be used in animal feed and are biodegradable. Tons of Sitagliptin are manufactured annually and the elimination of waste materials is having a marked effect on the company’s ecological balance sheet – and on its profitability.

Environmentally friendly and affordable

The environmental friendliness is a positive side effect that biocatalysis generates in the manufacture of medicines. Another is the fact that the drugs can be sold more cheaply on the market. Perhaps with a view to correcting the imbalance in medical care in developing countries, the researcher notes.

However, it will be a few years before the technology is ready for industrial use. The research effort is enormous. Kroutil compares the enzymes he uses with a complex ball of wool that makes the production of biocatalysts even more laborious. However, speedy and efficient manufacture is a prerequisite for the use of this integrated technology.