Synthesis of D- and L-phenylalanine derivatives by phenylalanine ammonia lyases: a multienzymatic cascade process.
The synthesis of substituted D-phenylalanines in high yield and excellent optical purity, starting from inexpensive cinnamic acids, has been achieved with a novel one-pot approach by coupling phenylalanine ammonia lyase (PAL) amination with a chemoenzymatic deracemization (based on stereoselective oxidation and nonselective reduction). A simple high-throughput solid-phase screening method has also been developed to identify PALs with higher rates of formation of non-natural D-phenylalanines. The best variants were exploited in the chemoenzymatic cascade, thus increasing the yield and ee value of the D-configured product. Furthermore, the system was extended to the preparation of those L-phenylalanines which are obtained with a low ee value using PAL amination.
Manchester Institute of Biotechnology and School of Chemistry, University of Manchester, 131 Princess Street, M1 7DN, Manchester (UK).
Fabio
F
Parmeggiani
Sarah L
SL
Lovelock
Nicholas J
NJ
Weise
Syed T
ST
Ahmed
Nicholas J
NJ
Turner
D000586:Amination; D046870:Anabaena variabilis / Q000201:enzymology*; D060326:Chemistry Techniques, Synthetic; D010084:Oxidation-Reduction; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D010650:Phenylalanine Ammonia-Lyase / Q000378:metabolism*; D013237:Stereoisomerism
D010649:Phenylalanine; D010650:Phenylalanine Ammonia-Lyase
amino acids; biocatalysis; enzymes; lyases; synthetic methods