A Multi-Enzymatic Cascade Reaction for the Stereoselective Production of γ-Oxyfunctionalyzed Amino Acids.
A stereoselective three-enzyme cascade for synthesis of diasteromerically pure γ-oxyfunctionalized α-amino acids was developed. By coupling a dynamic kinetic resolution (DKR) using an N-acylamino acid racemase (NAAAR) and an L-selective aminoacylase from Geobacillus thermoglucosidasius with a stereoselective isoleucine dioxygenase from Bacillus thuringiensis, diastereomerically pure oxidized amino acids were produced from racemic N-acetylamino acids. The three enzymes differed in their optimal temperature and pH-spectra. Their different metal cofactor dependencies led to inhibitory effects. Under optimized conditions, racemic N-acetylmethionine was quantitatively converted into L-methionine-(S)-sulfoxide with 97% yield and 95% de. The combination of these three different biocatalysts allowed the direct synthesis of diastereopure oxyfunctionalized amino acids from inexpensive racemic starting material.
Faculty of Biology and Biotechnology, Junior Research Group for Microbial Biotechnology, Ruhr-University Bochum Bochum, Germany.
Junichi
J
Enoki
Faculty of Biology and Biotechnology, Junior Research Group for Microbial Biotechnology, Ruhr-University Bochum Bochum, Germany.
Jaqueline
J
Meisborn
Faculty of Biology and Biotechnology, Junior Research Group for Microbial Biotechnology, Ruhr-University Bochum Bochum, Germany.
Ann-Christin
AC
Müller
Faculty of Biology and Biotechnology, Junior Research Group for Microbial Biotechnology, Ruhr-University Bochum Bochum, Germany.
Robert
R
Kourist
amino acids; asymmetric oxidation; dynamic kinetic resolution; enzyme reaction; isoleucine dioxygenase; multi-enzyme cascade reaction