Biocatalytic retrosynthesis: Redesigning synthetic routes to high-value chemicals

Modern tools for enzyme discovery combined with the development of increasingly reliable strategies for protein engineering have greatly expanded the range of enzymes with suitable properties for practical applications. This situation presents enormous opportunities for the design of sustainable biocatalytic strategies for the production of high-value chemicals. Here, we highlight recent contributions from our laboratory concerning ω-transaminases and monoamine oxidases, two enzyme classes that have been exploited for the industrial scale production of active pharmaceutical ingredients or key chiral intermediates. Firstly, we describe the development of novel ‘smart’ amine donors which overcome inherent challenges associated with controlling the equilibrium position of ω-TA catalyzed processes. Subsequently, we demonstrate how engineered variants of monoamine oxidase developed in our laboratory have been applied as biocatalysts for the synthesis of a diverse range of active pharmaceutical ingredients and alkaloid natural products. Through these illustrative examples, we hope to promote the wider application of enzymes within the synthetic community.