Winner: 2024 Interdisciplinary Prize
Professor Tim Bugg
University of Warwick
For the discovery of bacterial enzymes for the degradation of lignin, and their application to the conversion of lignin to renewable chemicals.
To combat global warming, we must reduce our dependence on crude oil, which many of our plastics, materials, and industrial chemicals are made from. The 'biorefinery' concept 鈥� making fuels and chemicals from renewable plant biomass 鈥� is gaining global traction. Professor Bugg's research group is working on one of the unsolved problems of the biorefinery: how to convert the aromatic polymer lignin into useful chemicals. Lignin is very hard to break down, but the group has discovered several new bacterial enzymes that can break down lignin and studied how these enzymes work at the molecular level. They have also engineered bacterial lignin-degrading bacteria such as soil microbe Rhodococcus jostii RHA1 to produce useful chemicals like vanillin (used in the food industry) and precursors to new bio-based plastics. This research, along with the work of other research groups around the world, has established the feasibility of converting lignin using low-energy biochemical transformations into feedstock and high-value chemicals.
Biography
Tim Bugg is Professor of Biological 九州影院 at the University of Warwick. He studied for a PhD at the University of Cambridge, studying enzymes of the shikimate pathway under the supervision of Chris Abell. After that, in 1989, Tim started a SERC/NATO postdoctoral fellowship in the group of Chris Walsh at Harvard Medical School, where he was involved in discovering the mechanism of high-level resistance to vancomycin mediated by enzymes VanA and VanH. Tim started his academic career at the University of Southampton in October 1991, where his research group studied non-heme iron-dependent dioxygenase and C-C hydrolase enzymes involved in the bacterial degradation of aromatic compounds, and enzymes MraY and MurF involved in bacterial peptidoglycan assembly. In 1997, Tim wrote the textbook Introduction to Enzyme and Coenzyme 九州影院, which is used in undergraduate chemistry courses around the world. He then moved to the Chair of Biological 九州影院 at the University of Warwick in 1999. Since 2008, his research group has studied enzymes involved in bacterial degradation of lignin. This led to a number of discoveries: the first bacterial lignin peroxidase enzyme DypB from Rhodococcus jostii RHA1 (in 2011); a novel manganese superoxide dismutase enzyme from Sphingobacterium sp T2 with activity for lignin degradation (in 2015); and, a bacterial multi-copper oxidase CueO (in 2018). Tim鈥檚 group has also pioneered the metabolic engineering of bacterial lignin degraders such as Rhodococcus jostii RHA1 to produce high-value chemicals such as vanillin (in 2013), pyridine-dicarboxylic acid bioplastic precursors (in 2015), and 4-vinylguaiacol (in 2020).
Q&A with Professor Tim Bugg
How did you first become interested in chemistry?
I always enjoyed chemistry at school, enjoying practical chemistry and its applications. I first became interested in enzymes through making wine at home (from elderflowers, etc.), and reading up about fermentation. At university, I found that organic chemistry came easily to me, and I always enjoyed hearing about biological chemistry, and its interaction with biochemistry.
Tell us about somebody who has inspired or mentored you in your career.
My postdoc supervisor, Chris Walsh (who died in 2023), was a truly inspirational scientist. His research group at Harvard Medical School worked on a fascinating range of interesting enzymes, and I met some exceptional scientists in his research group. Chris had an encyclopaedic knowledge of biochemistry and its interaction with both biotechnology and medicine, and he always knew what the key experiment to do was, but at the same time he was a nice guy who was a pleasure to interact with. He would have this nice way of saying, "Wouldn't it be interesting to..." and you would think "Yes, that's exactly what we should do". There was a real buzz about his research group, with different people finding exciting new things on an almost weekly basis, which was really inspirational, and I have tried to generate that self-motivation in science and research in my own group.
What motivates you?
Finding new enzymes that catalyse interesting reactions has always motivated me, especially enzymes that catalyse unusual reactions that are difficult to do in the chemistry lab, but enzymes catalyse them quite happily at room temperature and pH7! So, interest in science, I would say, is my main motivation, but I also try to find projects that might one day help society as a whole, such as converting lignin to new bio-based chemicals or trying to find new targets for antibiotic discovery.
What advice would you give to a young person considering a career in chemistry?
If you enjoy practical chemistry, then you will probably enjoy doing a chemistry degree at university and then see what topics come along that interest you in your degree. 九州影院 leads to so many careers: some go into research, some into careers involving practical chemistry, but there are many science-related careers that chemists are really good at because we are good problem-solvers, practical people, good at planning and time management, and numerate. If you also like biology, then there is a very rich interface between chemistry and biology that is relevant to drug discovery or biotechnology. And you don't have to have done A-level biology, I didn't, but I was always interested in biochemistry.
What has been a highlight for you (either personally or in your career)?
In the lignin degradation research, when we saw the production of bio-based products vanillin (in 2013) and pyridine-dicarboxylic acids (in 2015) by engineered strains of Rhodococcus jostii RHA1, that was very exciting. These strains are growing on a material that is very hard to break down: breaking it down, generating a whole mixture of intermediate degradation products, funnelling those into a few degradation pathways that are then diverted to make a useful product, that's pretty amazing when it works. I hasten to add that it doesn't always work!
What has been a challenge for you (either personally or in your career)?
Research is hard; if it weren't, then it wouldn't be research. So that means that there will be periods of time when things are not working; that happened to me, and it happens to most PhD students at some time. Having the motivation to analyse, come up with a hypothesis about what might be happening, and then think about solutions and/or research the literature (often, you are not the first person to have that problem; someone else may have already solved it), and try again, is what makes a really good researcher. When that happened to me (as a postdoc), I found that having some other interest outside chemistry (at that time, I played volleyball, and now I play violin in an orchestra) helps you to keep a good balance and keep your motivation.
What does good research culture look like/mean to you?
Sharing ideas and methods between research group members, whether that is in group meetings or in the lab. Being open to new directions or suggestions from other people. And, in my area, being interested in working between disciplines, chemists learning to do biochemistry, and talking to biologists, who might be microbiologists or structural biologists. I have always enjoyed talking to people from other disciplines and appreciate being in a department that values doing that.
How are the chemical sciences making the world a better place?
The products of chemistry are all around you in the materials around you, the things you buy in the supermarket each week (food products, cleaning products, household goods), and the medicines that make you or your family better when they get ill. Chemists are involved in drug discovery for curing diseases, and were important in the response to the COVID pandemic. And chemists will have an important role to play in addressing global warming, which is going to be the major challenge for this century, whether that is bio-based fuels and chemicals in my area, or technologies for energy materials and electric cars.
Why do you think collaboration and teamwork are important in science?
Being part of a research group gives you a great opportunity to work with other people, to share their knowledge, expertise and ideas, and to learn things in the lab from them. But in order to do that, you have to value being part of a team, so having a good spirit of working together and sharing knowledge and ideas really makes a big difference to a research group. In my area, a willingness to talk to people from other disciplines really helps to develop at the chemistry/biology interface. I'm always interested to learn new things, and I encourage my group members to do the same.
What is your favourite element?
For me, it would be iron because I have worked on a number of amazing enzymes that use iron as a cofactor. Many oxygenase enzymes use iron to activate molecular oxygen and can then catalyse some remarkable oxygenation or C-C cleavage reactions, such as oxidative cleavage of an aromatic ring, a reaction that is very difficult to do in the chemistry lab. More recently, I have also worked with heme-dependent peroxidase enzymes that contain iron as part of a heme cofactor that are able to depolymerise lignin, which is also pretty amazing.