Biocatalytic Recycling Cascades Combining Aldolases and Transaminases for the Stereo‐Controlled Synthesis of γ‐Hydroxy‐α‐Amino Acids

Recycling cascades combining aldolases and transaminases from biodiversity were designed for the stereoselective synthesis of various isomers of γ‐hydroxy‐α‐amino acids. Aldolases with opposite enantioselectivities were combined with a d ‐α‐transaminase to prepare in a single step, d ‐ syn or d ‐ anti ‐4‐hydroxyglutamic acid with high yield and stereoselectivity. Bioactive (2 S ,3 R ,4 S )‐4‐hydroxy‐isoleucine was also efficiently prepared via an aldolase‐transaminase recycling cascade. In that case, the unexpected high stereoselectivity was shown to result from the thermodynamically‐driven formation of a stable derivative of the product. This novel approach was applied to the synthesis of l ‐ syn and d ‐ syn ‐4‐hydroxynorvaline as well as for 3 new β‐branched‐γ‐hydroxy‐α‐amino acids, analogues of 4‐hydroxyisoleucine.