BioChem - DOS

One-pot biocatalytic synthesis of substituted D-tryptophans from indoles enabled by an engineered aminotransferase

ACS catalysis

Parmeggiani, Fabio; Rué Casamajo, Arnau; Walton, Curtis J. W.; Galman, James L.; Turner, Nicholas J.; Chica, Roberto A.

<P><SMALL>D</SMALL>-Tryptophan and its derivatives are important precursors of a wide range of indole-containing pharmaceuticals and natural products. Here, we developed a one-pot biocatalytic process enabling the synthesis of <SMALL>D</SMALL>-tryptophans from indoles in good yields and high enantiomeric excess (91% to >99%). Our method couples the synthesis of <SMALL>L</SMALL>-tryptophans catalyzed by <I>Salmonella enterica</I> tryptophan synthase with a stereoinversion cascade mediated by <I>Proteus myxofaciens</I><SMALL>L</SMALL>-amino acid deaminase and an aminotransferase variant that we engineered to display native-like activity toward <SMALL>D</SMALL>-tryptophan. Our process is applicable to preparative-scale synthesis of a broad range of <SMALL>D</SMALL>-tryptophan derivatives containing electron-donating or -withdrawing substituents at all benzene-ring positions on the indole group.</P><BR>[FIG OMISSION]</BR>

2019

American Chemical Society

2155-5435

9

4

pp.3482-3486

10.1021/acscatal.9b00739

http://click.ndsl.kr/servlet/OpenAPIDetailView?keyValue=05787966&target=NART&cn=NART96317497

amino acids; biocatalysis; enzymes; organic synthesis; protein engineering; rational design