With the help of special enzymes and a biocatalytic method developed at the TU Hamburg, drugs could be produced in a more environmentally friendly and cheaper way in the future.

To understand the following process, we first need to look inside our body cells: each of them derives its energy from adenosine triphosphate (ATP). This is a substance that serves the body as an energy carrier and is therefore referred to as the basic energy building block of life. A person needs several kilograms of ATP per day. Yet the human body only contains between 50 and 200 grams of this substance. How is this possible?

When ATP is consumed, adenosine diphosphate (ADP) and a free phosphate are produced. This releases energy that the body can use. The ADP is then regenerated back into ATP. This requires new energy from food. This cycle takes place within a few seconds. At a biochemical level, ATP therefore provides energy that enables reactions to take place that would not be possible without this energy supply. This energy is transferred to the starting materials of the desired chemical reaction with the help of biocatalysts (enzymes).

Use for drug production

This is not only possible in nature, but also in factories. Many consumer goods are manufactured using chemical processes. The more efficiently and sustainably these can be realized, the better. This saves money and resources. Enzymes are a sustainable alternative to classic inorganic catalysts. Biocatalysis is primarily used in the industrial production of complex organic molecules. For example, in the production of pharmaceuticals. Some newly developed drugs are produced with the help of ATP. This is simpler and cheaper than traditional chemical synthesis. However, the provision of ATP is still very expensive.

A team led by Jan-Ole Kundoch, a doctoral student at the Institute of Technical Biocatalysis, has therefore developed a better regeneration system as part of a DFG project under the direction of Prof. Andreas Liese in the working group of Dr. Daniel Ohde and in collaboration with colleagues from Bioprocess Engineering at TU Dresden. Their newly developed so-called enzymatic cascade is more robust and less expensive than the previous procedure. The extremely inexpensive ethylene glycol, which is also used in antifreeze, is now used as the starting material.

Finding optimal reaction conditions

As part of the project, which ran for almost four years, it first had to be clarified whether the envisaged procedure was even biochemically possible. The next step was to improve it and bring it closer to industrial scalability. Two factors were particularly relevant here. The method had to work reliably and the costs had to be lower than for the previous procedure.

A total of five biocatalysts are now working together simultaneously. All of them have their preferred environmental conditions such as temperature, pH value, salt concentration, concentration of the respective starting material and product. The major challenge in Kundoch's project was therefore to find reaction conditions under which this system runs optimally. “We must have carried out 1,000 experiments,” reports Jan-Ole Kundoch, ”and initially examined all the biocatalysts individually and then built up the system piece by piece by adding one more biocatalyst at a time. In the end, I then examined and optimized the entire system.”

Kundoch sums up: “In this case, biocatalysis offers a good alternative to conventional chemistry, which often has to resort to toxic and environmentally harmful solvents that are used at high temperatures.” In addition to lower wage levels, less stringent environmental regulations are the reason why a large proportion of pharmaceutical production now takes place in India or China. The new ATP synthesis would therefore facilitate the political goal of producing more medicines in Europe again. At the same time, production costs would fall, which would relieve the burden on the healthcare system and make it possible to supply the world's poor population with essential medicines.

“Incidentally, in future it will be possible to produce substances in this way that cannot be synthesized chemically,” adds Kundoch. This means that completely new remedies can be invented.

Further information

You can find more information at TUHH Open Research