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Biocatalytic Cascade Reaction for the Asymmetric Synthesis of L‐ and D‐Homoalanine
Author(s) -
Silva Marcus V. de M.,
Costa Ingrid C. R.,
de Souza Rodrigo O. M. A.,
Bornscheuer Uwe T.
Publication year - 2019
Publication title -
chemcatchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.497
H-Index - 106
eISSN - 1867-3899
pISSN - 1867-3880
DOI - 10.1002/cctc.201801413
Subject(s) - amino acid , methionine , chemistry , enantiomeric excess , enantioselective synthesis , enzyme , biocatalysis , alanine , stereochemistry , escherichia coli , catalysis , biochemistry , reaction mechanism , gene
Unnatural amino acids attract growing attention for pharmaceutical applications as they are useful building blocks for the synthesis of a number of chiral drugs. Here, we describe a two‐step enzymatic method for the asymmetric synthesis of homoalanine from L‐methionine, a cheap and readily available natural amino acid. First, the enzyme L‐methionine γ‐lyase (METase), from Fusobacterium nucleatum, catalyzed the γ‐elimination of L‐methionine to 2‐oxobutyrate. Second, an amino acid aminotransferase catalyzed the asymmetric conversion of 2‐oxobutyrate to either L‐ or D‐homoalanine. The L‐branched chain amino acid aminotransferase from Escherichia coli (eBCAT), using L‐glutamate as amino donor, produced L‐homoalanine (32.5 % conv., 28 % y, 99 % ee) and the D‐amino acid aminotransferase from Bacillus sp. (DATA) used D‐alanine as amino donor to produce D‐homoalanine (87.5 % conv., 69 % y, 90 % ee). Thus, this concept allows for the first time the synthesis of both enantiomers of this important unnatural amino acid.