α, α -Dihydroxy Ketones and 2-Amino-1,3-diols: Synthetic and Process Strategies Using Biocatalysts
H. C. Hailes,
P. A. Dalby,
G. J. Lye,
J. M. Ward.
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 α, α -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.
Keywords: Biocatalysis, transketolase, transaminase, dihydroxy ketones, 2-amino-1,3-diols, microwell studies, microfluidics, colorimetric assay, BiCE programme, TAm, TK, Li-HPA, LDA, ThDP
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