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

• Published in: Journal of organic chemistry Vol. 88; no. 2; pp. 852 - 862
• Main Authors: Tork, Souad Diana, Nagy, Emma Zsófia Aletta, Tomoiagă, Raluca Bianca, Bencze, László Csaba
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 20-01-2023
• Subjects: Amino Acids; Arabidopsis; Biocatalysis; Phenylalanine; Phenylalanine Ammonia-Lyase - chemistry; Phenylalanine Ammonia-Lyase - genetics; Phenylalanine Ammonia-Lyase - metabolism
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.2c02106

An efficient preparative-scale synthetic procedure of l-phenylalanine derivatives has been developed using mutant variants of phenylalanine ammonia-lyase from Arabidopsis thaliana (AtPAL). After 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)-m-methylphenylalanine; 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 space-time yields fulfill the requirements of sustainable and green chemistry, providing facile access to valuable amino acid building blocks.