‘Not everything we get from nature is nice’

Your inaugural speech had to be rescheduled due to the corona crises. What does that mean to you? 

“To be honest, not that much as it’s going to happen sooner or later. Actually, there are advantages. It will be later this year in summer, so the weather will be nicer. I had blocked a whole day for it, and now I have a whole day to get some work done. It’s a time gain that I had not expected.”

Your field of research is bio-catalysis. Can you explain what that is?

“What we do here is to use enzymes, natural catalysts, to reduce the chemical industry’s environmental pollution. I’m not saying ‘to make it green’ because that sounds like there will be no pollution at all. Instead, we believe that we can make industrial processes much better by using enzymes’ properties. For example, enzymes work at room temperature while a lot of chemical catalysts only work properly at very high temperatures. Initiating reactions at lower temperatures will save a lot of energy.

Another property of enzymes is that they are selective or even picky. Catalysts attach to molecules in different places simply because they can reach all those places. Enzymes will make sure that the molecule is only able to bind in one or very few places, so that only those places are attacked and react. That makes the enzyme more selective, resulting in better and safer products. And it’s fun! The fun factor is the real reason why we do chemistry at all to be honest.”

Talking of fun, what drew you into this field of research? 

“Coincidence really. I studied chemistry because I liked it for the reason that many little boys like chemistry: you can make things explode. That was the fun part. So I went to study chemistry and when I came to the point that I had to decide on where to do my master thesis, I chose the professor that looked the funniest. Professor Eberhard Steckhan was a fantastic guy at the University of Bonn.

He did electro-chemistry and he had a project on enzymes and electro-chemistry. That’s how I came into this field and how I came to work with enzymes. And I still work with them to this day. Honestly, it was not a decision that I consciously took because of scientific expectations. I really chose it because of Steckhan. Unfortunately, he died very early on in my career, in the first year of my PhD project with him.

It left us desperate, but I was lucky because I had been working with another group in Switzerland and they sort of adopted me. My PhD supervisor then became Professor Andreas Schmidt. Most of the time I choose things because they seem fun. I think that this is one of the best criteria.”

‘I’m spending more time here than with my wife, so I’d better make sure that I like what I do’

Do you also recommend it to your students?

“Yes, definitely. Research is interesting in many aspects. If I could choose again, I would do biology and botany. What all the plants and fungi do is so cool. It is really interesting and I would, and probably will, start studying botany. You can never predict what’s a good field of science, so the only criterion is to choose something that sounds interesting and exciting. Then go for it. I’m spending more time here than with my wife, so I’d better make sure that I like what I do.” 

You already mentioned it, but is bio-catalysis inherently green? 

“No. Everyone writes that bio-catalysis is green because it’s natural and bio. To be frank, I don’t like this romanticised view of bio-stuff. The most toxic poisons we have are bio-based! Not everything we get from nature is nice. Right now, everyone is very afraid of the coronavirus which is pure bio. You know, even when you do a reaction with an enzyme you still have to stir it. Stirring needs energy so you use energy resources to trigger reactions.

Bio-catalytic processes also pose a burden on the environment. I don’t like the bashing of chemistry – partly because I am a chemist myself, of course – but because chemistry is not that bad for some things. You cannot say that the enzymatic reaction will always be better than the chemical one. I teach my students that if you want to say it’s greener, do the calculations first. Perform a life cycle assessment to compare both processes and see which performs best overall. In many cases, bio-catalysis is much greener, but I’m reluctant to say that that’s always the case.” 

‘The only criterion for choosing something is if it sounds interesting and exciting. Then go for it’

What are the main hurdles in developing bio-catalysis?

“Right now, we are working with enzymes called peroxygenases. These are enzymes that perform selective hydroxylation. We insert an oxygen atom (O) into a carbon-hydrogen bond (C-H), which is a very difficult reaction, but these enzymes have evolved to do exactly this reaction. The peroxygenases are fun and interesting to use because they only use hydrogen peroxide (H2O2) to drive the reaction. But if you add too much, you inactivate the enzyme and it will die.

We have developed methods to keep the level of H2O2 at exactly the right level. The enzymes work and they’re not being killed. That was fun to do and we had to be very creative.

That’s the fun part of working at a university. We have developed a lot of methods that are very useful that may be directly used in industry. But we also have the time to play around and work with systems that to some sound crazy. I prefer the word ‘visionary’. For example we worked with colleagues from the Delft Reactor Institute using nuclear waste to make hydrogen peroxide.”

At inaugural speeches, the young professors usually outline their research plans. What are yours?

(Sigh) “This slide is still empty. I really don’t know. Working with these enzymes, these peroxygenases, at the moment is still a lot of fun, and I think we will continue working with them for the next few years because so few people work with them. So there are still a lot of white spaces on the map. That is the fun part. Not too long ago we started working with another enzyme just because we found it amusing. It’s an enzyme that uses light and is produced by algae. We read about it in Science and decided to work on it. It takes fatty acids and chops off the carboxylate group (-CH=O).”

Chemical decarboxylation reactions use very high temperatures. We like the idea: if this enzyme is in the dark, it doesn’t do anything. But if you shine a blue light – and it has to be blue – on it, it starts working. Now we realise there are many more applications. You can make new products and new things that no one has ever thought of. We are having fun playing around with this enzyme to see what we can do with it. And we’re pretty confident that researchers will continue discovering special enzymes.” 

Are you at the interface of the two worlds of chemistry and molecular biology?

“Ja, that’s exactly where we are. We are the chemists using enzymes and doing chemistry with them. We do not worry much about where they come from, even though there are fascinating things going on. We mostly care about the application of these enzymes in chemistry.”

That seems apt for a technical university

“Ja, ja. But there is a new trend. A friend of mine is working on resurrecting ancient enzymes. A bio-informatics approach allows you to compare different versions of an enzyme class, and you can then calculate back to what their earliest ancestor must have looked like. This method tells me that there are enzymes that have existed for billions of years. It’s a fascinating thought that you might be working with an enzyme that has been around for billions of years. Whether they are useful or not – we will find out.” 

• Prof.dr. Frank Hollmann (1973) studied chemistry at the University of Bonn (Germany).
• In 2004 he obtained his PhD from the Swiss Federal Institute of Technology with Andreas Schmid (Zürich, Switzerland).
• After a postdoc with Manfred Reetz (2004-2005 at the Max-Planck Institute for Coal Research, Mülheim/Ruhr, Germany) he worked for some years as R&D manager at Evonink Industries (Essen, Germany).
• Since 2008 he is member of the Department of Biotechnology at TUDelft and enjoys investigating possibilities of using enzymes to make chemical transformations more efficient. Particularly, his research focuses on specific oxyfunctionalisation reactions.