Engineered, Scalable Production of Optically Pure L-Phenylalanines Using Phenylalanine Ammonia-Lyase from Arabidopsis thaliana

An efficient preparative-scale synthetic procedure of Lphenylalanine derivatives has been developed using mutant variants of rigorous reaction engineering, the AtPAL-catalyzed hydroamination reaction of cinnamic acids provided several unnatural amino acids of high synthetic value, such as (S)-m- and (S)-p-methoxyphenylalanine; (S)-o- and (S)-mmethylphenylalanine; and (S)-o- and (S)-p-bromophenylalanine at preparative scale, significantly surpassing the catalytic efficiency in terms of conversions and yields of the previously reported PcPAL-based biotransformations. The AtPAL variants tolerated high substrate and product concentrations, representing an important extension of the PAL-toolbox, while the engineered biocatalytic procedures of improved E-factor and spacetime yields fulfill the requirements of sustainable and green chemistry, providing facile access to valuable amino acid building blocks.

Automated summary

An efficient preparative-scale synthetic procedure of L-phenylalanine derivatives has been developed using mutant variants of rigorous reaction engineering. The AtPAL-catalyzed hydroamination reaction of cinnamic acids provided several unnatural amino acids of high synthetic value, significantly surpassing the catalytic efficiency of previously reported PcPAL-based biotransformations. The AtPAL variants tolerated high substrate and product concentrations, representing an important extension of the PAL-toolbox, while the engineered biocatalytic procedures of improved E-factor and spacetime yields fulfill the requirements of sustainable and green chemistry, providing facile access to valuable amino acid building blocks.