Engineered Biocatalysts for the Asymmetric Synthesis of d-Phenylalanines

Abstract

The enzymatic synthesis of d-phenylalanines, important chiral building blocks for several pharmaceuticals and fine chemicals, has been widely explored. Their asymmetric synthesis of high atom economy and accessible prochiral starting materials is highly attractive, while the expanding toolbox of protein engineering facilitates access to biocatalysts tailored for these processes. Accordingly, this Review provides an overview of the protein engineering efforts of enzymes involved in the asymmetric synthetic pathways for d-phenylalanines. The engineering efforts on d-amino acid dehydrogenases, d-amino acid transaminases, and phenylalanine ammonia-lyases to produce d-phenylalanines are thoroughly examined, while their application in (chemo)enzymatic cascades is also discussed. For an improved efficiency of the cascades, the protein engineering of l-amino acid deaminases and/or l-amino acid oxidases for an increased transformation of phenylalanines is also addressed.