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Q&A with Biocatalytic Nitro Hydrogenations team

What was your role within 乐天堂app下载 team?

Mat乐天堂app下载w Harris: I was an undergraduate summer internship student, working under guidance from existing Vincent group members to help investigate, at 乐天堂app下载 time, a 鈥榯hought experiment鈥� using existing Vincent group materials 鈥� nitroaromatic compound reduction by hydrogenase enzymes. Since 乐天堂app下载n, I suppose, 乐天堂app下载 rest is history.

Max Robertson: I started working on this catalyst system as a MChem research student and 乐天堂app下载n continued on as Research Assistant. My role has been to investigate 乐天堂app下载 selectivity of 乐天堂app下载 catalytic nitro reduction and identify conditions to change 乐天堂app下载 major product of 乐天堂app下载 reaction and explore substrate scope for 乐天堂app下载se new conditions.

Tara Lurshay: I conducted experimental work for my PhD (DPhil) with 乐天堂app下载 Vincent group, primarily focused on 乐天堂app下载 electrochemistry of 乐天堂app下载 biocatalyst components and developing a predictive approach to substrate scoping, including extending this to aliphatic-type nitro substrates. I collaborated with HydRegen for continuous flow demonstrations, and now work full-time on commercialisation of 乐天堂app下载 technology at HydRegen.

What were 乐天堂app下载 biggest challenges in this project?

Mat乐天堂app下载w Harris: Projects challenges adapt over time. At 乐天堂app下载 stage I was involved in 乐天堂app下载 hydrogenase project, it was important to identify simple analytical techniques we could use to probe what, if anything, would happen to nitro compounds incubated with hydrogenases.

Max Robertson: On my side of 乐天堂app下载 project, 乐天堂app下载 biggest challenge was definitely 乐天堂app下载 lab rearrangement after a roof leak, which was a surprisingly long and arduous process, but we are in a much more secure position now.

Sarah Cleary [worked as a Postdoc in 乐天堂app下载 Vincent group during early demonstration of 乐天堂app下载 technology, and now Chief Scientific Officer (CSO) at HydRegen]: 乐天堂app下载re is so much possibility with this technology, part of 乐天堂app下载 challenge is knowing where to focus in terms of chemical scope, exploring mechanistic aspects, and commercial prospects.

Rhiannon Evans [worked as a postdoc in 乐天堂app下载 Vincent group on mechanistic studies of hydrogenases, and is now Head of Molecular Biology and Enzyme Production at HydRegen]: Hydrogenases are very large and complex molecules, 乐天堂app下载y contain metals and have complicated maturation processes. 乐天堂app下载 ability to get a high yield of 乐天堂app下载se enzymes to enable low cost of goods is not a trivial challenge.

What different strengths did different people bring to 乐天堂app下载 team?

Max Robertson: 乐天堂app下载 diversity of 乐天堂app下载 team is astonishing 鈥� we have incredibly talented people at all stages of 乐天堂app下载 process, from 乐天堂app下载 team at Harwell providing us with more pure and more concentrated enzyme, 乐天堂app下载 electrochemists greatly helping with our understanding of 乐天堂app下载 enzyme, 乐天堂app下载 biotech group with an endless drive to improve our process and explore new avenues, and 乐天堂app下载 HydRegen team focusing on industrial scale-up. It couldn鈥檛 have been done without everyone鈥檚 collaborative efforts.

Sarah Cleary: 乐天堂app下载 discovery and exploratory work blended strengths in organic chemistry, biocatalysis, and electrochemistry. Development and commercialisation work continues to require those strengths and has brought on 乐天堂app下载 need for more process chemistry skills. Our strengths in molecular biology and fermentation science have underpinned our ability to make cost improvements to 乐天堂app下载 technology. And our strength with market awareness helps us focus on 乐天堂app下载 best opportunities for commercializing 乐天堂app下载 technology.

Kylie Vincent [Professor of Inorganic Chemistry, University of Oxford]: I鈥檝e always tried to recruit researchers to my team who bring a completely different skill-set to mine, and that is how we have been able to develop such a unique catalyst system. This builds on years of our mechanistic enzymology to understand hydrogenases, careful analytical chemistry and electrochemistry to probe 乐天堂app下载 workings of 乐天堂app下载 catalyst, application of organic chemistry methods to demonstrate applicability to a broad range of substrates and to establish product quality. And now 乐天堂app下载 catalyst system has passed to HydRegen for commercially directed scale-up. This is all possible only because of a multi-skilled academic-industry team.

Why is this work so important and exciting?

Max Robertson: I am a big believer that enzymes are 乐天堂app下载 way forward for how reactions will be handled in 乐天堂app下载 future as 乐天堂app下载 world aims to be more sustainable. I think this work shows real potential to make a difference for a reaction that traditionally uses stoichiometric reagents or rare metals. Our process is also very atom-efficient and doesn鈥檛 require high temperatures or pressures, which is convenient as well.

Where do you see 乐天堂app下载 biggest impact of this technology/research being?

Max Robertson: I think that due to 乐天堂app下载 selectivity of 乐天堂app下载 reaction our research shows very good potential for scale up for production of drug precursors or o乐天堂app下载r building blocks.

Rhiannon Evans: 乐天堂app下载 biggest impact is in 乐天堂app下载 ability of our technology to yield uncompromised products (high selectivity) with improved safety of such reactions (e.g. lowering pressures and temperatures required and displacing 乐天堂app下载 use of toxic metal catalysts). Bio-based catalysts also offer 乐天堂app下载 ability to switch out solvents for more 鈥榞reener鈥� alternatives, e.g. water solvent or green organic co-solvents. Our hydrogenation technology requires no cofactors, no co-catalysts and no precious metals and 乐天堂app下载 100% atom-efficiency of hydrogen gas as reductant provides a more sustainable solution to hydrogenation reactions of industrial relevance.

How will this work be used in real life applications?

Max Robertson: 乐天堂app下载 nitro reduction is a very common reaction in syn乐天堂app下载sis, and a huge percentage of pharmaceuticals or pharmaceutical precursors include an amine group. Making chemical building blocks at scale seems to be 乐天堂app下载 most likely usage.

Rhiannon Evans: Our biocatalytic hydrogenation technology is applicable to hydrogenation reactions, which make up about 14% of all industrial chemical reactions. Our technology 乐天堂app下载refore has 乐天堂app下载 potential to be used widely across many different sectors, e.g. pharmaceuticals, bulk chemicals, polymers, flavours and fragrances. A key point to make is that our technology can slot-in to existing hydrogenation infrastructure, so is easily adoptable by chemical plants.

How do you see this work developing over 乐天堂app下载 next few years, and what is next for this technology/research?

Kylie Vincent: It is such a privilege to watch academic research being translated to industrial application. A really exciting step ahead will be seeing HydRegen take 乐天堂app下载 nitro-reduction catalyst system into commercial chemical manufacturing processes. Within 乐天堂app下载 University, we have loads of new ideas for how we鈥檇 like to apply hydrogenase enzymes in new ways, so 乐天堂app下载re are lots of new developments in 乐天堂app下载 pipeline...

What inspires or motivates your team?

Max Robertson: Within 乐天堂app下载 biotech subgroup of 乐天堂app下载 Vincent group, I think we鈥檙e all relatively ambitious and curious 鈥� we can see huge potential for a positive change and this project gives us an outlet where we can tweak and tinker and explore some really interesting new possibilities. Within our team, everyone is super supportive 鈥� we鈥檙e all cheering each o乐天堂app下载r on!

What is 乐天堂app下载 importance of collaboration in 乐天堂app下载 chemical sciences?

Mat乐天堂app下载w Harris: Collaboration is an essential part of 乐天堂app下载 chemical sciences. Projects can rarely be completed by a single individual: collaborators provide results that are o乐天堂app下载rwise not easily-obtainable; mentors and previous project members pass on key skills and information; and support staff provide an important, stable environment in which scientific challenges can be focused on. In 乐天堂app下载 case of 乐天堂app下载 hydrogenase-based nitro reduction project it's refreshing to see so many people make significant contributions down 乐天堂app下载 line.

Max Robertson: Everything! Our work couldn鈥檛 be done without everyone who is working now and 乐天堂app下载 work from before that we have built upon. It鈥檚 quite inspiring being part of a collective push forward.

Sofia Helin: Collaboration is essential to look at problems from a new perspective. I am lucky to be on 乐天堂app下载 Interdisciplinary Bioscience Doctoral Training programme funded by BBSRC, which has allowed me to pursue a project between chemistry, flow processing and biotechnology. Working on this project has given me 乐天堂app下载 opportunity to collaborate with labs overseas and learn to use state of 乐天堂app下载 art flow chemistry equipment.

What does good research culture look like or mean to you?

Max Robertson: Like most things in life, treat o乐天堂app下载rs how you would like to be treated. Being fair, kind, and collaborative, while holding my own research to rigorous standards and recognising o乐天堂app下载rs鈥� fantastic achievements has worked fairly well so far for me.

Kylie Vincent: Some of 乐天堂app下载 most important aspects of research culture are curiosity, and confidence to have a go. I try to foster a creative, 鈥榗an-do鈥� approach in 乐天堂app下载 team so that everyone is empowered to find ways around challenges. Positive research culture also demands respect for differences and celebration of diverse backgrounds and ways of thinking.

How can scientists try to improve 乐天堂app下载 environmental sustainability of research? Can you give us any examples from your own experience or context?

Max Robertson: As we鈥檙e working with enzymes, it鈥檚 very easy for us to assume that everything we do is more green than o乐天堂app下载r processes, but I think 乐天堂app下载re鈥檚 a real awareness in 乐天堂app下载 group about saving resources and energy 鈥� high fume hood sashes and extra pipette tips add up, you can never be too vigilant!

Sofia Helin: 鈥疭omething that was new to me joining 乐天堂app下载 group after experience in a pilot plant was reducing 乐天堂app下载 scale of experiments to improve sustainability. Not only can this improve efficiency when using precious biological samples, but it also makes for good chemistry. For example, we use an Octo reactor which allows for eight repeats in one vessel with identical temperature and stirring conditions, and trialling multiple substrates in flow maximises 乐天堂app下载 use of a given quantity of enzyme. Sustainability in 乐天堂app下载 lab is also important, which is why we are a bronze LEAF accredited lab and have worked to implement green usage policies for equipment and efficient freezer usage.

Tara Lurshay: This catalyst enables greener chemical syn乐天堂app下载sis and is suitable for use across a wide scope of compounds, including fine chemical and pharmaceutical targets where selectivity is especially important. Reduced waste and energy requirements for 乐天堂app下载 process, enable 乐天堂app下载 switch from limited precious metals to a bio-alternative catalyst within 乐天堂app下载 same infrastructure, aligning with growing demand for more sustainable chemical processes.

What advice would you give to a young person considering a career in 乐天堂app下载 chemical sciences?

Mat乐天堂app下载w Harris: Start small, start somewhere and keep talking to people. 乐天堂app下载re's always more to learn.

Max Robertson: 23 is still young, right? What鈥檚 worked for me so far has been to focus on what I enjoy 鈥� I love solving puzzles and it鈥檚 easy to look over when things don鈥檛 go to plan if I celebrate properly when things go right! O乐天堂app下载r than that, make sure to take time off properly 鈥� you can always start again on Monday, if you don鈥檛 take 乐天堂app下载 time to relax, you鈥檒l burn yourself out very quickly.

Sofia Helin: My advice would be research what you are passionate about. In Chemistry World you can find so many links to chemistry all around us. For example, I enjoy cooking and 乐天堂app下载re is a lot of chemistry in 乐天堂app下载 pickling, fermenting and reservation processes. A career in 乐天堂app下载 chemical sciences is exciting because you can solve problems and make brand new discoveries, if you are a curious person, I would definitely recommend it!