Lipase/Transaminase Reaction Cascade for the Synthesis of β‐Amino Acids

[1] S.-H. Wu, Z.-W. Guo, C.J. Sih, Enhancing the Enantioselectivity of Candida Lipase Catalyzed Ester Hydrolysis via Noncovalent Enzyme Modification ,J. Am. Chem. Soc., 112, p. 1990-1995 (1990) [2] C. Crismaru, G. Wybenga, Biochemical properties and crystal structure of a beta-phenylalanine aminotransferase from Variovorax paradoxus, Appl. Environ. Microbiol., 79, p. 185-195 (2013) [3] R. Bach, C. Canepa, Electronic Factors Influencing the Decarboxylation of‚-Keto Acids. A Model Enzyme Study., J. Org. Chem., 61, p. 6346-6353 (1996) [4] D. Seebach, K. Gademann, Mixed β-peptides : A Unique Helical Secondary Structure in Solution, Helv. Chim. Acta, 80, p. 2033-2038 (1997) Result purified and active (S)-selective ω-transaminase (Fig. 1) successful screening of active Lipases and an Esterase capable of converting b-keto acid esters (Fig. 2) establishing of High Throughput Assays for the detection of enzyme activity Fig.2: Specific activtiy of lipase/esterase with different β-keto acid esters as substrate. Fig. 1: Kinetic resolution of rac β-phenylalanine catalyzed by crude cell extract and purified (S)-selective ω-transaminase respectively. The aim of this study is to hydrolyze the β-keto acid esters with a lipase to β-keto acids (Fig. 2), acting as precursors for the synthesis of the corresponding β-amino acids catalyzed by an (S)-selective ω-transaminase [1] [3] (Fig. 1 + 3). The problem we have to face here is the spontaneously decarboxylation of b-keto acids. On this occasion we have to freshly prepare the precursors for the following transamination.