Sustainable routes to anti-infective agents to combat future pandemics.

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There is an urgent need for new anti-infective agents to combat antimicrobial resistance and to protect the global population in the event of future pandemics. The majority of drugs used to treat infectious diseases today are small molecules produced by microorganisms, called natural products, or derivatives thereof. The existing anti-infective agents have become less effective as pathogens evolve resistance to these molecules. Consequently, we need to discover new anti-infectives and also develop methods to diversify/optimise the structure of these molecules if we are to combat emerging antimicrobial resistance (AMR) and provide treatments for future pandemics. In this project, we aim to use state-of-the-art synthetic biology technologies, novel enzymes and integrated catalysis to create novel antibiotics and new anti-viral agents. Enzymes offer the advantage that they are highly selective, sustainable catalysts that function under mild conditions, in water. Conversely, traditional synthetic chemistry methods can require high temperatures and deleterious solvents. Synthetic chemistry can also be non-selective which is wasteful as by-products are produced that are difficult to separate. We will also develop biocatalysis and integrated biocatalysis approaches (Industrial biotechnology) to create methods to novel compounds in a cleaner and more sustainable manner minimising work up between steps. Training will be provided in biological chemistry, catalysis, biochemistry, enzymology, structural biology (X-ray crystallography), directed evolution and synthetic biology