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. Graphic Abstract: [Figure not available: see fulltext.]