How did you get interested in Chemical Biology?

Early on in my chemistry studies I became intrigued by the synthetic potential of enzymes and our budding capability to engineer them into even more useful catalysts.

Where and when did you obtain your PhD diploma?

I obtained my PhD diploma from ETH Zurich in 2011 with Professor Donald Hilvert. I worked on the “Directed Evolution of Artificial Enzymes”: Using an in silico designed enzyme as a starting point, we evolved the new-to-nature biocatalyst to exhibit “natural” enzyme-like activity.

After my PhD, I started to work in industry (Firmenich SA) and led a laboratory for biocatalytic transformations to obtain fragrance and flavour compounds.

Where are you currently working and what is your current position?

I’m a Professor at the Zurich University of Applied Sciences and lead the Competence Center for Biocatalysis (www.zhaw.ch/ccbio) where we work on engineering enzymes for challenging chemistries (e.g., stereocontrolled halogenation) and developing new enzyme engineering techniques.

How would you explain what your research area is to non-scientists?

Enzymes are Nature’s catalysts and drive chemical processes in all living things. Enzymes possess many desirable characteristics: they are highly specific, work in water, are biodegradable and can be produced sustainably. 

Nature has optimized enzymes for their tasks over many billions of years and found solutions to highly complex problems. Our goal is to tailor the biocatalysts to address challenges in the chemical industry, e.g., the sustainable production of drugs, flavours, or agrochemicals.  

In a way, the development of a biocatalytic reaction can be compared to top-level sports. In a first step, one scouts for talent – in our lab that means to identify wildtype enzymes that are in principle capable of catalysing the desired reaction. Next comes training: In our case, this corresponds to the directed evolution of enzymes through recurrent cycles of diversification and selection in the laboratory. Finally, we develop a “game strategy” for the tailored biocatalysts by optimizing reaction parameters such as temperature, pH, substrate, and solvent concentrations.  

What do you like best about your work?

The freedom to constantly learn and discover new things leading to wonderful “Heureka” moments.

How many PhD students and postdocs do you currently supervise?

Currently, we are a team of 6 PhD students & 10 postdocs/ research associates; We are always happy to welcome new enzyme enthusiasts to our team. Currently, we are looking for a bioinformatician and a biocatalysis postdoc.

How would you describe yourself as a supervisor?

Curious, excitable, willing to listen and learn.

What do you consider your greatest achievement in your scientific career?

I am proud of developing enzymes which find meaningful practical applications.  

Which of your papers are you most proud of and why?

J. Büchler, S. Honda Malca, D. Patsch, M. Voss, N. Turner, U. Bornscheuer, O. Alleman, C. Le Chapelain, A. Lumbroso, O. Loiseleur and R. Buller, Algorithm-aided engineering of aliphatic halogenase WelO5* for the asymmetric late-stage functionalization of soraphens, Nat Commun 2022, 13, 371. 

The paper highlights how elegantly enzymes can do very complex chemistry.

M. Eichenberger*, S. Hüppi*, D. Patsch*, N. Aeberli, R. Berweger, S. Dossenbach, E. Eichhorn, F. Flachsmann, L. Hortencio, F. Voirol, S. Vollenweider, U. Bornscheuer and R. Buller, Asymmetric Cation-Olefin Monocyclization by Engineered Squalene-Hopene Cyclases, Angew Chem Int Ed2021, 60, 26080 – 26086.

Leveraging our understanding of the enzymatic mechanism, we employed substrate engineering to access the desired product enantiomer.

What are the features of a successful PhD student or postdoc?

Curiosity, drive, resilience, and passion for science.

What advice would you give to someone who wants to know more about your field? 

Attending conferences and getting in touch with experts in the field. I feel that interdisciplinary discussions are the most rewarding!

What is the most embarrassing thing you have done in the lab while doing experiments, e.g. explosions?

The most embarrassing experience was during my diploma thesis: When plating bacterial cells next to a Bunsen burner I set a bit of my hair on fire. I looked funny for the rest of the semester.

What would you expect to be the next major breakthrough in chemical biology?

• Enzymatic synthesis of customized DNA.
• Leveraging AI to better understand the sequence-function relationship in enzymes.

The 1st International Meeting, Molecules4Life (1M4Life), occurred between the 20-22^nd of September 2023 at the School of Life and Environmental Sciences of the University of Trás-os-Montes and Alto Douro. The firsts congress with the Molecules4Life seal was a joint organization of the Centro de Química-Vila Real (CQVR) and the Portuguese Chemical Society. This first edition was dedicated to the interaction between new molecules and Health Sciences, and important advances achieved with new molecules or new molecular configurations were addressed in 4 major topics: Healthy Food (HF), Drug Delivery (DD), Therapeutic Applications (TA) and Sensing and Diagnosis (SD).

The congress featured ten plenary conferences, seven invited communications, 28 oral presentations, 50 posters and around 140 participants from various parts of the country (including the Azores and Madeira) and also from the United States, France, Germany, Ireland, Scotland, Spain, South Korea, Malaysia, Turkey, England, Poland, and Croatia. Most participants were university professors or postdoctoral researchers. Several doctoral and master's students also participated, especially from UTAD.

The plenary conferences addressed the most recent advances, challenges, and trends in the different themes of the congress. They were given by:

• Prof. Richard Hartley (Univ. of Glasgow) – "Small molecules to interrogate and intervene in cellular redox."
• Prof. Tiago Outeiro (Univ. of Gottingen) – "Unraveling the molecular mechanisms of Parkinson's disease and related synucleinopathies"
• Prof. Matilde Marques (IST) – "Tackling health challenges with chemical tools: incursions into drug design and drug toxicity"
• Prof. Belen Vaz (Univ. of Vigo) – "Synthesis of indolebenzoazepinone scaffolds as active epigenetic modulators: challenges and opportunities"
• Dr Bruno Silva (Empa) – "Advances and challenges in nonviral gene therapeutics: a physical chemist's perspective"
• Prof. Maria Blanco-Prieto (Univ. of Navarra) – "Nanomedicine for the treatment of pediatric cancer"
• Dr. Rui Campos (IINL) – "Genosensors: from small molecules to nucleic acids"
• Prof. Maria Gamella-Carballo (UCM) – "Disposable affinity electrochemical biosensing platforms: towards reliable tools for food safety and personalized nutrition"
• Prof. Pierre-Louis Teissedre (Univ. of Bordeaux) – "Health potential of grape and wine phenolic compounds"
• Prof. Justin Siegel (UC Davis) – "Protein design and discovery to build the future of our food system".

At 1M4Life, the best oral and poster communications in each area were awarded, with the jury made up of several members of the scientific committee. The winners in the best Oral Communication category were João Siopa (UTAD) in HF, Daniela Malafaia (UA) in TA, Ivo Martins (UMA) in DD and Isilda Amorim (UM) in SD. The prizes for best posters were awarded to Mónica Silva (UTAD) in HF, Beatriz Morais (IST) in TA, Marina Amorim (UP) in DD and Joana Martins (UC) in SD.

1M4Life was a success, with excellent plenary communications that provided valuable insights, stimulated critical thinking, and promoted productive dialogues among participants. In addition to the plenary sessions, the event offered networking opportunities that further enriched the relationship between researchers.

The Molecules4Life Organizing Committee would like to thank all participants for the high quality of the work presented and all sponsors for supporting this event.