There is increasing interest in the use of biocatalysts in synthetic applications due to their ability to achieve highly stereoselective and atom efficient conversions. Recent developments in molecular biology techniques and synthetic biology have also enhanced potential applications using non-natural substrates. Here we review strategies to , '-dihydroxy ketones and 2-amino-1,3-diols via the use of transketolase, a carbon-carbon bond forming biocatalyst, and the enzyme transaminase which converts aldehydes and ketones to amines. Using an integrated strategy we have investigated new chemistries and assays, identified novel biocatalysts and used directed evolution strategies, together with miniaturization studies and modelling to achieve rapid and predictive process scale-up.The use of biocatalysts for the synthesis of biologically active compounds is of increasing interest to the chemical, pharmaceutical and biotechnology sectors in the search for sustainable, cost effective, synthetic strategies. In addition, developments in molecular biology tools and protein and pathway engineering, leading to improved biocatalyst substrate tolerance, specific activities and processing properties are resulting in extensive possibilities for the use of enzymes in synthesis. Current interest in synthetic biology approaches and also cascade reactions, with applications in biofuel synthesis as well as routes to pharmaceuticals, will result in exciting developments and opportunities using biocatalysts in the next decade. At UCL, a multidisciplinary approach has been established in the Departments of Chemistry, Biochemical Engineering and Structural and Molecular Biology (BiCE programme) focusing initially on biocatalytic approaches to , '-dihydroxy ketones and 2-amino-1,3-diols [1]. This has led to the development of new biocatalysts and chemistries and new miniaturization tools for rapid and predictable process scale-up. This review will focus on the use of two enzymes, transketolase (TK) (EC 2.2.1.1) and transaminase (TAm) for the synthesis of the important structural motifs , '-dihydroxy ketones and 2-amino-1,3-diols and biocatalyst scale-up tools.

No abstract