Applications of enzyme cascades in organic synthesis

Enzymes are increasingly applied as biocatalysts in organic chemistry, in particular for reactions that require a high degree of chemo-, regio- and stereo-selectivity. An additional advantage of biocatalysis is that reaction conditions are very similar in terms of temperature, pressure, pH and solvent. Both the selectivity and the compatibility of biocatalysts enable the design of multistep reaction cascades, as seen in many biosynthetic pathways in Nature. The toolbox of diverse biocatalysts that have become available to the organic chemist is now rapidly expanding due to in vitro evolution and genomic data-mining techniques. As a result, the scope for assembling multi-enzyme pathways by linking diverse biocatalytic steps guided by considerations of organic retrosynthesis is feasible. Here we present several examples of multienzymes cascades from our recent work, that can generate high value compounds in one pot reactions either in vitro or in whole cell systems. Examples include biomimetic cascades for the synthesis of complex glycopeptides containing O-mannosyl tetrasaccharides, cascades that accomplish formal stereoselective C-H aminations at non-functionalised carbon centres and cascades that generate chiral nitrogen heterocycles from oxo-carboxylic acids.