In 2022, University of Toronto Professor Jik Chin (Chemistry) was awarded a Climate Positive Energy grant for his research on the production of unnatural amino acids using his chiral guanidines. That same year, graduate student Rick Fu was awarded a CPE Graduate Research award for his project examining guanidines as a motif for carbon capture and activation, supervised by Professor Chin. Nearly two years later, Rick is now nearing the end of his PhD program, entering the consulting industry, and on a pathway to commercialize the graduate work he performed under the supervision of Professor Chin.
“We are told that climate change is caused by an increase in carbon dioxide concentrations in the atmosphere, and so carbon dioxide has sort of taken on the reputation of a ‘villain,’” explains Professor Chin. “It has become common thinking that carbon dioxide is a ‘bad’ molecule, but that couldn’t be further from the truth: every single carbon atom in our body is derived from CO2, as nature is able to transform CO2 into all organic matter through a series of enzymatic reactions.”
The researchers explain that many of these transformations require an essential cofactor called biotin. Biotin is one of the B vitamins. It’s involved in a wide range of anabolic and catabolic processes, both in humans and in other organisms, primarily related to the synthesis and breakdown of fats, carbohydrates, and amino acids. “It’s a part of biological machinery,” adds Rick. However, biotin requires enzymes to be activated.
Inspired by nature, Professor Chin and Rick are developing guanidine-based synthetic mimics of biotin that do not require enzymes. Another potential advantage of these synthetic mimics is that the scope of the carboxylation reaction need not be limited to biological reactions.
Rick’s research surrounding biotin is two-fold: (1) to gain an increased understanding of biological biotin catalyzed reactions, and (2) to develop novel biotin mimetics to catalyse CO2 transformation reactions that nature cannot.
“Our interest in developing methods to synthesize unnatural amino acids started with our Nature publication in 1999 where we reported the first synthetic complex that can bind amino acids with high specificity,” explains Professor Chin. “Later, we refined our approach and reported a receptor in 2007 that can interchange the handedness of amino acids.” A version of this fundamental approach ended up in the creation of a ~$100M (USD) Korean-based company named AminoLogics.
Over the last decade, Professor Chin’s team has continuously improved their systems to develop the latest generation of methods to synthesize unnatural amino acids. Synthetic amino acids are common building blocks of pharmaceuticals and are found in several blockbuster drugs. Their process of generating a large library of amino acid building blocks could significantly expedite the drug discovery process, while reducing the amount of chemical waste generated.
Chiral guanidines have been developed in Professor Chin’s laboratory for two unrelated applications. The first is for making unnatural amino acids and the second is for mimicking biotin. As a result of the CPE research award, the research team was able to scale up their work for making unnatural amino acids. They have also shown that unlike biotin, guanidines can efficiently capture CO2 without the need for enzymes. The goal is not only to capture CO2 with guanidines, but also to catalyze carboxylation reactions like biotin-dependent enzymes. Such catalysts could be useful not only for biological reactions but also a wide variety of chemicals including fertilizers like urea or drugs like aspirin.
As a result of their CPE membership, Professor Chin and Rick have also connected with other research groups to advance their project, including researchers at U of T in chemical engineering and pharmacy programs. By attending events such as CPE Research Day, the group was able to expand their network and identify other groups and experts at the university that are working to advance sustainable research initiatives. The group also credits to CPE a connection to the University of British Columbia, for potential collaboration. In spring of this year, they will be manufacturing unnatural amino acids at UTM SpinUp facility for startup companies.
“Through the gracious support of Climate Positive Energy, we were able to scale our amino acid process from bench-top milligram scale to near kilogram scale, with the goal of commercializing our unnatural amino acid libraries,” says Rick. “Impact only happens when you can translate your research into the real world. It is only when research is translated into the real world may it have any impact at mitigating or solving climate issues, and the CPE grant has allowed us to have a chance at translating our research into the real world.”
“Nature has perfected catalytic recycling of CO2,” adds Professor Chin. “Every carbon atom in life from proteins to DNA come from CO2 and eventually they are recycled back to CO2. This remarkable feat is achieved by enzyme catalyzed carboxylation and decarboxylation reactions. If we can mimic even just a fraction of what nature can do and apply our understanding of biological recycling of CO2 to environmentally useful reactions, it would go a long way to solving the problems of our planet including pollution and energy.”