82795-51-5Relevant articles and documents
Simultaneous Preparation of (S)-2-Aminobutane and d -Alanine or d -Homoalanine via Biocatalytic Transamination at High Substrate Concentration
Li, Jianjiong,Wang, Yingang,Wu, Qiaqing,Yao, Peiyuan,Yu, Shanshan,Zhu, Dunming
supporting information, (2022/03/01)
(S)-2-Aminobutane, d-alanine, and d-homoalanine are important intermediates for the production of various active pharmaceutical ingredients and food additives. The preparation of these small chiral amine or amino acids with high water solubility still demands searching for efficient methods. In this work, we identified an ω-transaminase (ω-TA) from Sinirhodobacter hungdaonensis (ShdTA) that catalyzed the kinetic resolution of racemic 2-aminobutane at a concentration of 800 mM using pyruvate as the amino acceptor, leading to the simultaneous isolation of enantiopure (S)-2-aminobutane and d-alanine in 46% and 90% yield, respectively. In addition, (S)-2-aminobutane (98% ee) and d-homoalanine (99% ee) were isolated in 45% and 93% yield, respectively, in the kinetic resolution of racemic 2-aminobutane at a concentration of 400 mM coupled with deamination of l-threonine by threonine deaminase. We thus developed a biocatalytic process for the practical synthesis of these valuable small chiral amine and d-amino acids.
Enantioselective Synthesis of d- and l-α-Amino Acids by Enzymatic Transamination Using Glutamine as Smart Amine Donor
Heuson, Egon,Charmantray, Franck,Petit, Jean-Louis,de Berardinis, Véronique,Gefflaut, Thierry
, p. 778 - 785 (2019/01/04)
Enzymatic transamination is a useful method for the green and highly enantioselective synthesis of chiral amines and non-canonical amino acids which are of major importance as intermediates in medicinal chemistry. However, transamination reactions are usually reversible and synthetic applications of transaminases often require the implementation of an equilibrium shift strategy. Herein, we report a highly effective approach using glutamine as smart amine donor. This amino acid is converted upon transamination into 2-oxoglutaramate which undergoes a fast cyclisation displacing the transamination equilibrium. We have developed a new activity assay in order to identify transaminases from biodiversity able to convert various α-keto acids into valuable amino acids of l- or d-series in the presence of glutamine as amine donor. Discovered transaminases were then used to prepare in high yield and with high enantioselectivity three amino acids of pharmaceutical importance, homophenylalanine, homoalanine and tert-leucine by simply using a nearly stoichiometric amount of glutamine as amine donor. (Figure presented.).
Structure-guided engineering of: Meso -diaminopimelate dehydrogenase for enantioselective reductive amination of sterically bulky 2-keto acids
Cheng, Xinkuan,Chen, Xi,Feng, Jinhui,Wu, Qiaqing,Zhu, Dunming
, p. 4994 - 5002 (2018/10/17)
meso-Diaminopimelate dehydrogenase (DAPDH) and mutant enzymes are an excellent choice of biocatalysts for the conversion of 2-keto acids to the corresponding d-amino acids. However, their application in the enantioselective reductive amination of bulky 2-keto acids, such as phenylglyoxylic acid, 2-oxo-4-phenylbutyric acid, and indole-3-pyruvic acid, is still challenging. In this study, the structure-guided site-saturation mutagenesis of a Symbiobacterium thermophilum DAPDH (StDAPDH) gave rise to a double-site mutant W121L/H227I, which showed dramatically improved enzyme activities towards various 2-keto acids including these sterically bulky substrates. Several d-amino acids were prepared in optically pure form. The molecular docking of substrates into the active sites of wild-type and mutant W121L/H227I enzymes revealed that the substrate binding cavity of the mutant enzyme was reshaped to accommodate these bulky substrates, thus leading to higher enzyme activity. These results lay a foundation for further shaping the substrate binding pocket and manipulating the interactions between the substrate and binding sites to access highly active d-amino acid dehydrogenases for the preparation of synthetically challenging d-amino acids.
