Asymmetric synthesis of aromatic β-amino acids using ω-transaminase: Optimizing the lipase concentration to obtain thermodynamically unstable β-keto acids

• Published in: Biotechnology journal Vol. 11; no. 1; p. 185
• Main Authors: Mathew, Sam, Jeong, Seong-Su, Chung, Taeowan, Lee, Sang-Hyeup, Yun, Hyungdon
• Format: Journal Article
• Language: English
• Published: Germany 01.01.2016
• Subjects: Amino Acids, Aromatic - chemical synthesis; Amino Acids, Aromatic - chemistry; Keto Acids - chemistry; Lipase - analysis; Lipase - metabolism; Molecular Structure; Protein Stability; Thermodynamics; Transaminases - metabolism; Biocatalysis; Asymmetric synthesis; Unnatural amino acid; Beta amino acids; ω-transaminase
• ISSN: 1860-7314
• DOI: 10.1002/biot.201500181

Synthesized aromatic β-amino acids have recently attracted considerable attention for their application as precursors in many pharmacologically relevant compounds. Previous studies on asymmetric synthesis of aromatic β-amino acids using ω-transaminases could not be done efficiently due to the instability of β-keto acids. In this study, a strategy to circumvent the instability problem of β-keto acids was utilized to generate β-amino acids efficiently via asymmetric synthesis. In this work, thermodynamically stable β-ketoesters were initially converted to β-keto acids using lipase, and the β-keto acids were subsequently aminated using ω-transaminase. By optimizing the lipase concentration, we successfully overcame the instability problem of β-keto acids and enhanced the production of β-amino acids. This strategy can be used as a general approach to efficiently generate β-amino acids from β-ketoesters.