Biocatalytic Decarboxylation of Aromatic l-Amino Acids with In Situ Removal of Both Products for Enhanced Production of Biogenic Amines

Abstract

Biogenic amines are important messengers in neurotransmission, drawing attention to pharmaceutical applications. Here, we developed a novel biocatalytic process for the preparation of biogenic amines using aromatic l-amino acid decarboxylase (AADC) under an in situ product removal (ISPR) condition. The AADC from Bacillus atrophaeus (AADC-BA) showed broad substrate specificity for aromatic amino acids, affording > 90% conversions of 10 mM substrates to corresponding products: 2-phenylethylamine (2-PEA), tryptamine, serotonin, and dopamine. Owing to enzyme inhibitions by the reaction products, we implemented an ISPR strategy using a cation exchange resin and an open reactor system for removal of amine and CO2, respectively. Under the open-air conditions, the addition of Dowex 50WX8 afforded 81% conversion of 100 mM l-phenylalanine to 2-PEA within 1 h, whereas 56% conversion was obtained without the resin. The ISPR strategy enabled the preparative-scale production of serotonin from 5-hydroxy-l-tryptophan (405 mg), yielding > 99% conversion within 40 min.