Opportunities and challenges for combining chemo- and biocatalysis

The past decade has seen a substantial increase in successful examples of the combination of chemo-and biocatalysis for multistep syntheses. This is driven by obvious advantages such as higher yields, decreased costs, environmental benefits and high selectivity. On the downside, efforts must be undertaken to combine the divergent reaction conditions, reagent tolerance and solvent systems of these 'different worlds of catalysis'. Owing to progress in enzyme discovery and engineering, as well as in the development of milder and more compatible conditions for operating with various chemocatalysts, many historical limitations can already be overcome. This Review highlights the opportunities available in the chemical space of combined syntheses using prominent examples, but also discusses the current challenges and emerging solutions, keeping in mind the fast progress in transition metal-, organo-, photo-, electro-, hetero- and biocatalysis.