9.15 Industrial Applications of Asymmetric Synthesis using Cross-Linked Enzyme Aggregates

Biocatalysis has many attractive features for industrial-scale enantioselective synthesis. Enzymes are derived from renewable materials and are biodegradable. Reactions are generally performed in water under mild conditions, in high (enantio)selectivities, and without the need for protection/deprotection and activation steps. For commercial viability, however, it is often necessary to immobilize the enzyme, affording improved stability and facile recovery and reuse. Immobilization as cross-linked enzyme aggregates (CLEAs) has additional advantages compared with alternative methods for immobilization of enzymes. The procedure is simple, does not require highly pure enzymes, has a broad scope and affords robust, recyclable catalysts with good activity retention. The use of CLEAs from various enzymes – proteases, amidases, lipases, nitrilases, nitrile hydratases, hydroxynitrile lyases – in enantioselective syntheses is described. A combi CLEA containing three enzymes – an ( S )-hydroxynitrile lyase, a nitrilase, and an amidase – catalyzed the highly enantioselective (>99% enantiomeric excess ( ee ) formation of ( S )-mandelic acid from benzaldehyde and hydrogen cyanide. It is concluded that CLEAs have potential for wide application in enantioselective biocatalysis at industrial scale.