St Vincent Research

[Annegret Haldiman]

TheVincent group were delighted to host 3 undergraduate summer research students in summer '23: Nomagugu Moyo, Grace Elliott-Sherratt and Pedro Theodoro. Their projects have opened new directions in our research: thanks for all your hard work, and to the group for hosting so well.

Our research is mainly in the areas of bioinorganic chemistry and chemical biology or industrial biotechnology. We are driven by the excitement of discovering fundamental mechanisms of catalysis in biology, and the possibilities for exploiting biocatalysis in new ways for chemical synthesis.

The activation of small molecules in biology is a key research theme in the Vincent group. Chemists have a lot to learn from catalytic processes which occur in microorganisms. For example, nature has tuned hydrogenase enzymes to oxidise and produce H2 efficiently at earth-abundant iron or nickel-iron catalytic sites. Nitrogenase catalyses the fixation of N2 to ammonia under mild conditions. Carbon dioxide reducing enzymes fix CO2 selectively into CO or formate. These chemical reactions represent some of the greatest chemical challenges for solving the world's energy problems, and we hope that what we learn from studying the biocatalytic reactions will inspire development of new catalysts for energy technologies. The Vincent group has developed a suite of spectroscopic techniques that bridge gaps between measurements of enzyme activity, spectroscopy and structure. With significant funding from the BBSRC and the European Research Council (ERC) we are employing these to great effect in probing the mechanisms of metalloenzymes involved biological hydrogen, carbon and nitrogen cycles.

In parallel we are excited by the interface between academic discovery and technology innovation. We have developed and patented a H2-driven approach to heterogeneous biocatalysis, known as the HydRegen system. This bridges the advantages of clean, metal-driven hydrogenations and selective biocatalysis under mild conditions. By immobilising all the enzymes for a desired C=X bond reduction on a carbon support, we enable heterogeneous biocatalytic hydrogenations which can be readily translated into continuous flow processes. We have extended this to biocatalytic deuterium insertion, to H2-driven flavin recycling, to continuous flow reactors and to chemo-bio catalytic cascades. With significant funding from Innovate UK, EPSRC and BBSRC, and close industrial collaborations, we are taking some of these areas forward to commercialisation. The company HydRegen was spun out from the University of Oxford in 2021 with former group member, Dr Holly Reeve, as CEO. Within the Vincent group, we continue to innovate in the biocatalysis area.

We are a friendly, sociable research group, and we really value our diverse membership. We celebrate the mix of cultures represented in the group, and the creative-thinking that comes from a neuro-diverse, gender-balanced and LGBTQ+ -inclusive team. We value innovation and a 'can-do' attitude towards solving challenges in research.

Please do get in touch if you would like to hear more about opportunuities in the Vincent group. We always welcome applications from qualified students or postdoctoral scientists with scholarships or fellowships to support their research, or candidates seeking to apply for Oxford scholarships or fellowships. As a group we span a broad range of subject expertise: from bio-inorganic or bio-physical chemistry to synthetic organic chemistry to structural and molecular biology.

The Center is interdisciplinary. Students learn qualitative and scientific methods along the entire spectrum, from conception to measurement to analysis. Their work is driven by their own ideas and passions, and held up for public inspection. All research at Mount Saint Vincent conforms to national standards of ethics. It allows students to develop methodological skills, and encourages them to develop an expertise in a given area of research. Students do well in this environment, and have been invited to present their work at national and international conferences. The University holds an annual research symposium featuring original student scholarship in which more than 80 students have presented their research.

The Center has a record of sponsoring students engaged in overseas research. For example, a nursing major embarks on a qualitative interviewing project in Vietnam to study alternative medicine. A dual English and Teacher Education Major travels to the Thai-Burmese border to conduct participant observation research while teaching and assisting in a system of border schools that serves children who are Burmese migrants and refugees. Other students have conducted a field survey of Day Laborers in a nearby urban environment on behalf of Catholic Charities, and has performed the data analysis for a national quantitative survey for the National Association of Ethnic Studies.

The Center is pioneering advocacy research focused on studying vulnerable populations and the environment. In conjunction with partners, the Mount is initiating the Listening Project in social development research. Social development policy is too often characterized by more powerful actors dictating to those in need. The Listening Project is predicated on the idea that in order to develop sound social policy, it is essential to listen to vulnerable populations and those who serve them on the ground level.

Vincent du Vigneaud was born in Chicago, Illinois on May 18, 1901. He died on Dec. 11, 1978. During his 77 years, he achieved much in the field of biochemistry and received many honors, including the Nobel Prize in Chemistry.

During World War II, du Vigneaud and his coworkers took time from their study on sulfur metabolism to attempt to synthesize penicillin. In November of 1946 they announced their achievement, the isolation in crystalline form of the active synthetic G-penicillin, and du Vigneaud returned to his primary field of interest. The investigation at his laboratory at CUMU involved cysteine-containing polypeptide hormones of the pituitary gland. Oxytocin, the uterine contracting and lactation-inducing hormone, was isolated in 1949, as was vasopressin, the antidiuretic hormone, a few years later. In October of 1953, du Vigneaud announced the synthesis of oxytocin. It was for this achievement, which necessitated the development of many new research techniques and opened a new area in protein organic chemistry, that Vincent du Vigneaud received the Nobel Prize in Chemistry in 1955.

Du Vigneaud received many other honors throughout his lifetime including the Nichols Medal from the American Chemical Society (1945) and the Lasker Award (1948). He was a visiting lecturer throughout the United States and Europe. His book, A Trail of Research, was the result of the Messenger Lectures delivered at Cornell University in 1950. As might be expected, Vincent du Vigneaud was an active member of many professional societies including the National Academy of Sciences and an honorary member of others.

We are particularly interested in small molecule activation at metal sites in enzymes. Chemistry has a crucial role to play in solving the pressing global challenges of sustainable energy supply, and capture and use of carbon dioxide. In these areas, nature has already established exquisitely tuned enzymes as catalysts. Redox enzymes play key roles as catalysts in biological cycling of hydrogen, carbon and nitrogen and energy. Their active sites are built from common metals such as iron, nickel and copper, and the reactivity achieved at these biological metal centres is often difficult to replicate under ambient conditions with synthetic catalysts. We are interested in understanding details of the redox chemistry and mechanisms of catalysis occurring at enzyme active sites. A central theme in our research is to bridge the gaps between different techniques in bioinorganic chemistry. We combine electrochemistry and spectroscopy to control and study enzymes as they engage in catalytic turnover. We apply these approaches to single crystals of enzymes to bridge the gaps between solution and solid state measurements and reveal structures of catalytically active intermediates. Our studies target a range of metalloproteins including hydrogenases, nitrogenase, carbon monoxide dehydrogenase and nitric oxide sensing proteins. We are particularly interested in the efficient catalysis of H2 oxidation and production by microbial hydrogenase enzymes at [NiFe] active centres. Ligands at the active site of hydrogenases, CO and CN-, give rise to fairly intense absorption bands in the Infrared spectrum. This has inspired us to develop new approaches to infrared spectroelectrochemistry for studying hydrogenase active site chemistry under direct electrochemical control. Understanding and exploiting selective nature's catalysts should provide inspiration for development of new classes of energy-cycling catalysts.

We are also fascinated by applications of enzymes in chemical synthesis. We have developed and patented the HydRegen system for C=X bond hydrogenations via H2-driven recycling of the biological hydride transfer cofactors, NADH and NADPH. This offers the best of both worlds between the impressive selectivity of biocatalysis on the one hand, and the atom-efficiency and ease of implementation of hydrogenations (which are typically catalysed by precious metals). We have demonstrated this approach for a varienty of C=X bond reductions, using a wide range of NAD(P)H dependent enzymes, including keto reductases, imine reductases, ene reductases and amino acid and amine dehydrogenases. We are working closely in collaboration with industry to develop the HydRegen system for industrial fine chemical synthesis. In recent work, we have extended this approach to selective biocatalytic deuterium insertion, and operated many of our biocatalytic reactions in continuous flow.

Kylie Vincent's research is supported by the EPSRC, BBSRC and InnovateUK, and the European Research Council. We are also supported by collaboration with a variety of industrial partners including Johnson Matthey and Dr Reddy's.

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