Industrial chemical production goes green: researchers harness nature's chemical producers
Conventional industrial chemical production requires harsh conditions and environmentally unfriendly processes to transform raw materials like crude oil into useful chemicals and plastics. But imagine if nature's own chemical cell factories could turn cheap starting materials such as organic waste leftover from farming or food processing into recyclable components for the chemical industry.
In living organisms, biochemical reactions are taking place all the time – turning nutrients into useful products – facilitated by specialized proteins known as enzymes. These biological catalysts or biocatalysts can be harnessed to accelerate other types of reactions for industrial chemistry – but under much milder conditions.
Wolf-Dieter ‘Woody’ Fessner
This is the vision of ‘green’ industrial chemistry held by researcher Wolf-Dieter ‘Woody’ Fessner of the Technische Universität Darmstadt, who is coordinating the € 8.2 million EU-funded project CarbaZymes.
This four-year project, which began in April last year, is bringing together European universities, SMEs, a research institute and multinational company to develop sustainable industrial processes based on enzyme catalysts.
The innovation could transform the chemical sector into a greener and more sustainable industry. Fessner explains how.
How did you become interested in this topic?
I’ve been working in science for quite a long time but, when I started out as a chemist, the area was completely different – the principles of a sustainable green chemistry had not yet been formulated. When I had to decide about my future career, and where I could see the future of my discipline, I was fascinated by the selectivity of biocatalysis using enzymes, which was completely new to me. As an organic chemist you play around with simple molecules, but in biocatalysis you are also tinkering with the complex tools of nature, which have evolved over millions of years.
What issue do you hope to tackle with the project?
Industrial chemical processes convert ordinary bulk commodities into more valuable products by catalytic reactions on an enormous scale. Typically, these processes make larger molecules from smaller pieces. This requires the formation of new bonds between carbon atoms – something that is extremely challenging to do with complete selectivity for synthetic organic chemists like me. Most of the reaction processes that create new carbon-carbon bonds require harsh conditions at high temperatures, use corrosive reagents or toxic metals and produce enormous amounts of waste.
Enzymes have been optimized by nature for making natural products from nature’s own starting materials – not the products that industry requires. So we are trying to develop improved enzyme catalysts for new reactions that will make the desired industrial chemicals under ecologically favourable conditions.
That’s the background chemistry to why enzymes make interesting catalysts for synthetic chemistry. And they should help make the chemical industry more sustainable.
What is the aim of the project?
First of all, the type of reactions we are investigating in CarbaZymes, carbon-carbon bond formation using enzymes, is a completely underdeveloped area of enzyme catalysis. Most people believed that such enzymes were too specific and could not be utilized under industrial constraints. But we would like to overcome this.
Enzymes have evolved in many different environments; some are quite delicate, unstable or sensitive, which makes working with them difficult and renders them unsuitable for technological applications. But, of course, nature has also developed many organisms that live in extreme conditions – some even thrive in boiling water, for example – so their enzymes must be tolerant too.
We ‘just’ have to find them, tailor them and utilize them for industrial purposes.
What are the advantages of enzyme catalysts?
Using enzymes as catalysts enables mild reaction conditions to be used – such as ambient temperatures and water as a solvent, which is much more environmentally benign. Unlike traditional metal catalysts, enzymes are not toxic.
Enzymes also have another advantage, I believe, over chemical catalysts. Chemical catalysts can be modified by adding chemical groups known as ligands to set their selectivity and catalytic activity, but optimizing the ligands is quite a tedious process. With protein catalysts, optimization is becoming much easier.
Because a wealth of structural information about proteins is available, we can rationally engineer enzymes to optimize their properties and develop novel reactions and processes for making molecules that, up to now, could only be made economically by chemical reactions under harsh, ecologically problematic conditions that produce a lot of waste and consume a lot of energy.
Like the optimization of traditional catalysts, rational protein engineering can also be a tedious process. But, alternatively, we can utilize the drive of evolution to modify protein catalysts. Without any detailed knowledge, we can employ random mutagenesis or environmental DNA cloning techniques and simply select or ‘screen’ for those catalysts that work best for a particular industrially relevant reaction or conditions.
Once identified, your biocatalyst can simply regrow itself whenever needed, rather than having to synthesize it from scratch each time anew.
What could be the impact of the project?
Developing enzymes to catalyse carbon-carbon bond formation could have a major impact on the development of new processes in industry. By replacing old and ecologically problematic reactions, enzyme biocatalysis could make a real difference to chemical production methods in the future. Once the technology is in place for individual examples, others will follow and I believe that it may ultimately have a ‘greening’ effect on the entire chemical industry.
You have to remember that bulk chemicals are produced in the billions of tons and that if these processes can be modified to be more environmentally friendly it will definitely have an impact on our planet. And it’s just the beginning.
And don’t forget the ‘valley of death’! Developments in the lab are only on the small scale. Scale up to the multi-ton scale required by industry is really difficult and not usually something that academics like me care about. That has led to the unfortunate situation where the results of much academic research are not carried over to industrial applications. To bridge this gap – the so-called valley of death – is very important, I believe, and a fundamental goal of our consortium.
What has been the most exciting aspect of the project for you so far?
A colleague in our consortium has already discovered an enzyme and developed this catalyst to produce the desired product under unbelievable conditions that are really close to industrial requirements. Even I, with all my experience, thought this would be really challenging because of the high reactivity of the ingredients. We have already filed a patent – which is quite some achievement, I believe, given the short time for which the project has been running. That is, for me, truly amazing!
So I think we are on the right track and there will be many other developments that could be potentially patentable and useful for industrial applications. We have a number of further enzymes under scrutiny for similar purposes, which we are screening for improvement. And we have already identified some interesting hits. I think our approach is quite promising.
How did you become involved in this project and find your partners?
I did not create the CarbaZymes consortium… a consortium grows! It starts with colleagues discussing ideas with other colleagues and somehow a picture forms.
In Europe, we have an ideal situation for that, I believe, through COST – the long-running European Cooperation in Science and Technology framework programme. This initiative funds thematic networks – such as our current action on systems biocatalysis – that foster interactions between scientists – we can exchange students, acquire new techniques, or hold specialist meetings. Although there is relatively little money involved, it is an excellent platform for exchanging ideas and is quite instrumental as an incubator for setting up smaller partnerships that can lead to larger projects.
What are the benefits of being part of an EU project?
You can achieve many things through simple national or one-on-one collaborations, of course. But for the bigger picture, projects require more knowledge and more resources. With a more challenging project, you need to work with specialists with access to the mist advanced technologies with whom you do not usually collaborate on a routine basis, and that’s only possible in larger consortia with a common perspective.
Participating in such an endeavour is certainly very stimulating and rewarding. For the coordinator, of course, there is a bureaucratic pill to swallow but you get a lot of freedom to operate on new ground. And, of course, it is possible to make a much larger impact and achieve something significant with such a team that you could not by yourself or with one or two colleagues.
What are your key ingredients for a successful project?
Excellent partners, creativity and determination! The key ingredients to be successful are sufficient imagination to craft the idea and then persistence to keep going until you reach the ultimate goal. Of course, you need a lot of scientific input and technical expertise from others but without the original vision, this will never lead to something useful.
What advice would you give?
Just try! It is very likely that your first proposal will fail – but you always have the chance to improve it and try again. Don’t hesitate to reapply. By working with other people and developing ideas together, you develop innovative perspectives. By thinking about new problems, you enhance your independent creativity.
Finally, I believe we are doing something really important! Of course, the future and results of our CarbaZymes project are unforeseeable, but knowing that scientists like us are working hard to improve tomorrow’s technologies from today’s perspective is, I think, reassuring.