Vincent's group

The Vincent group is based in the #Chemistry Department at the University of Oxford, UK. We are a primarily a bio-inorganic research group, with an interest in small molecular activation at metal centres in #enzymes. We have worked on #hydrogenase enzymes for several decades. These enzymes are inspirational to chemists because they use a catalytic site built from earth-abundant metals - nickel and/or iron - to activate hydrogen gas. In contrast, chemists still rely heavily on precious metals such as platinum or palladium for activating hydrogen. The Vincent group have developed a range of tools for studying the mechanism of the highly active #hydrogenase enzymes by coupling #electrochemistry with spectroscopy. We make extensive use of infrared spectroscopy, which reports on the vibrational changes at CO and CN- ligands at the active site of hydrogenases, while using electrochemistry to switch on/off #catalysis during measurements.

More recently, we have demonstrated #electrochemical control over single crystals of hydrogenase, allowing us to collect X-ray diffraction structures in well-defined redox states relevant to the catalytic cycle. This makes important links between observations made on solution samples and crystals of these enzymes. We have built up a significant structural biology sub-group, and are extending these approaches to other #metalloenzymes with roles in small #molecule activation, such as nitrogenase.

Our work on hydrogenases led us into biotechnology about 12 years ago. In particular, we became interested in more #sustainable ways of driving biocatalysis, replacing carbon-based reductants with hydrogen gas. We have developed #hydrogen-driven systems for recycling the reduced cofactors NADH and NADPH and flavins for application in biotechnology, and more recently we have developed a biocatalytic system for hydrogen-driven reduction of nitro-group to amines. We are also developing methods for reductant supply to dioxygen-dependent enzymes using safe mixtures of dihydrogen/dilute dioxygen. A key motivation for us is to make #bicoatalysis easier to operate, more atom-efficient, and more sustainable.

Our catalyst developments for #biotechnology are informed by our use of electrochemistry: we study enzyme #redox reactions as separate half reactions at an electrode, for example, the oxidation of dihydrogen, or the reduction of NAD+, allowing us to combine components in unique ways on electrically-conductive supports. We take inspiration from the model of ‘mixed potential theory’ discussed in heterogeneous catalysis. Our favourite support material is #carbon black, since it is already well-established as an industrial catalyst support and allows facile immobilisation of enzymes by direct adsorption. Since the enzymes are immobilised on carbon particles, these heterogeneous biocatalyst systems are ideal for translation into continuous flow, and we have applied #biocatalytic hydrogenations in continuous flow.

HydRegen

HydRegen is pioneering a novel #biotechnology that utilises the best and most robust components from nature to drive a step-change in #sustainable chemical manufacturing. A 2021 spinout from the University of Oxford, HydRegen offers the potential for cleaner, safer, faster and cheaper @chemical manufacture.

The chemicals sector underpins almost all manufacturing industries, turning raw materials into the chemicals we rely on every day, like medicines, flavours and fragrances for our foods and cosmetics and more. But the sector is under a lot of pressure, from political, societal, regulatory and financial bodies to clean up and address its sustainability issues. HydRegen is passionate about reducing the environmental impact of chemical manufacturing and committed to enabling companies across the chemicals sector to improve their energy and resource efficiency whilst moving towards continuous manufacturing processes.

The novel and patent-protected biotechnologies were first demonstrated by co-founder and CEO, Holly Reeve, during her undergraduate and PhD research at the University of Oxford and has since been taken from academic demonstrations to disruptive, industry-ready advanced manufacturing tools. With a specialised knowledge of complex biological systems, its proprietary #enzyme-based platform enables the power source for biocatalysis to be switched from glucose to #hydrogen gas, reducing its environmental impact. By replacing finite resources for hydrogenation reactions, like metal catalysts, with environmentally and economically sustainable alternatives, it is enabling energy-intensive businesses to reduce their carbon footprint.

HydRegen’s biotechnologies bring together #EU capabilities in modern chemical manufacturing and the rapidly growing bio-manufacturing ecosystem, uniquely allowing the chemical precision of biology to be implemented in existing chemical manufacturing infrastructure. Using ground-breaking technologies, HydRegen is at the forefront of pioneering bio-based metal replacements in hydrogenation reactions to enable these processes to be conducted under safer, more energy-efficient conditions with renewable biocatalysts. By addressing the unmet needs in industrial decarbonisation, HydRegen is enabling the uptake of innovative technologies that will play a critical part in the chemical sector meeting #NetZero 2050 goals across the EU, #UK and ultimately globally.

Protein Design Lab (Weizmann Institute)

Sarel Fleishman is a professor and head of the Protein Design Lab (https://lnkd.in/d2Su-kEK) at the Weizmann Institute of Science in Israel. The lab specializes in developing one-shot methods for designing #enzymes and #biologics. Some of the methods developed by the lab, such as PROSS and FuncLib, have become state-of-the-art in computational optimization of protein stability, expression levels, and activity. These and other tools are accessible to all scientists through web servers (https://lnkd.in/dsbe2zHY) and have resulted in more than 100 peer-reviewed papers and patent filings. These methods have served as the basis for founding two #biotechnology startups: Scala Biodesign specializes in optimizing biologics and enzymes, and Plantae Bioscience optimizes the health and nutritional value of crops.

The W-BioCat project will put the reliability of the lab’s design methods to a stringent test. Instead of designing just one enzyme at a time, this project calls for co-optimization of an entire enzymatic pathway. The lab will combine new methods in #AI-based structure prediction of enzymes with its proven methods for improving heterologous expression levels and specific activity. It will collaborate with other teams in the consortium to select the most promising enzyme targets for design, test the predictions, and improve the designs.

The ability to design optimal enzymatic pathways will be a landmark for promoting #sustainable #biocatalytic solutions to complex chemical synthesis challenges. We are eager to contribute to this effort!