Novel flow devices and development of process automation for H2-driven biocatalysis

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In the pharmaceutical industry, over 90% of synthesis proceeds using at least one catalytic step. In practise, this often means that expensive heavy metals such as palladium are being used at high pressures and temperatures to improve the rate of reactions. As well as the obvious safety and environmental costs, traditional metal catalysts can have selectivity issues, especially when used to make chiral centres. In the pharmaceutical industry, chiral centres are key - demonstrated by the case of thalidomide. By contrast, biocatalysts operate at room temperature and exhibit excellent selectivity due to their unique active sites. However, these require expensive additional cofactors, such as NADH, to function. To make the process cost efficient, the cofactors must be recycled, but current recycling systems create large amounts of carbon based waste. This project investigates a biocatalytic system made from an NADH-dependent enzyme carrying out a chiral reduction paired with a wasteless NADH recycling system, immobilised onto a solid support. Hydrogen is used to power the enzymes and the system will be adapted to flow chemistry. Flowing reagents through a reactor has proven to be safer and more energy efficient than similar batch processes. The focus of this project is to improve understanding of the enzyme NADH recycling system under flow conditions as well as demonstrating scale up in commercially available flow reactors.