2935-35-5Relevant articles and documents
Highly stereoselective recognition and deracemization of amino acids by supramolecular self-assembly
So, Soon Mog,Moozeh, Kimia,Lough, Alan J.,Chin, Jik
, p. 829 - 832 (2014)
The highly stereoselective supramolecular self-assembly of α-amino acids with a chiral aldehyde derived from binol and a chiral guanidine derived from diphenylethylenediamine (dpen) to form the imino acid salt is reported. This system can be used to cleanly convert D-amino acids into L-amino acids or vice versa at ambient temperature. It can also be used to synthesize α-deuterated D- or L-amino acids. A crystal structure of the ternary complex together with DFT computation provided detailed insight into the origin of the stereoselective recognition of amino acids. A communal effort: A chiral guanidine derivative 1 and a chiral aldehyde 2 underwent self-assembly with amino acids to promote inversion of the stereogenic center of the guest (see scheme). The supramolecular self-assembly exhibited high stereoselectivity for amino acid recognition and was found to be useful for the separation of racemic mixtures of amino acids as well as for their deracemization. Copyright
Stereoselective hydration of (RS)-phenylglycine nitrile by new whole cell biocatalysts
Hensel, Martina,Lutz-Wahl, Sabine,Fischer, Lutz
, p. 2629 - 2633 (2002)
Five new bacterial isolates with stereoselective nitrile hydratase activity against (RS)-2-phenylpropionitrile and (RS)-phenylglycine nitrile were investigated. The permeabilized whole cell isolates selectively hydrate the (S)-enantiomer of phenylglycine nitrile with E values of 1.2-5.4. One isolate, which was identified as Pantoea endophytica, produced pure (S)-phenylglycine (>99% ee) as a result of hydrolysis of (S)-phenylglycine amide by an (S)-specific amidase. Surprisingly, in the hydrolysis of (RS)-phenylglycine nitrile, it was found that the (R)-amide was accumulated in excess (21% ee) despite the nitrile hydratase produced by Pantoea endophytica was (S)-selective. The synthesis of pure (R)-phenylglycine (>99% ee) was achieved in time course studies using another Pantoea sp. with (R)-selective amidase. In the case of Nocardioides sp. the intermediate product, (S)-phenylglycine amide, could be produced (52% ee) without its subsequent hydrolysis into the acid due to the apparent absence of any amidase activity.
Directed evolution of formate dehydrogenase and its application in the biosynthesis of L-phenylglycine from phenylglyoxylic acid
Bai, Fang-Hui,Kan, Yun-Chao,Lu, Yun-Feng,Shi, Hong-Ling,Tang, Cun-Duo,Xie, Yu-Li,Yang, Tian-Tian,Yao, Lun-Guang,Zhang, Si-Pu,Zhang, Zheng-Hua
, (2021/08/09)
Formate dehydrogenase (FDH) is a D-2?hydroxy acid dehydrogenase, and catalyzes the oxidation of formate to carbon dioxide, coupled with reduction of NAD+ to NADH that plays a key role in the process of NADH regeneration. In order to obtain high activity formate dehydrogenase mutants, the formate dehydrogenase CbFDHC23S was used as the parent to conduct two rounds of directed evolution, and a mutant M2 was obtained which specific activity was about 4 times more than the parent and was more suitable for coenzyme regeneration under physiological conditions. Then, the molecular mechanism of temperature characteristic and catalytic efficiency change was preliminarily elucidated by computer-aided method. Finally, an engineered E. coli strain was established to co-express formate dehydrogenase and L-leucine dehydrogenase and enantioselectively transform phenylglyoxylic acid to give L- phenylglycine (e.e. >99%), the yield and space-time yield of L- phenylglycine can reach 90.46% and 82.07 g?L?1?d?1. This study laid a theoretical foundation for the green biosynthesis of food additives such as chiral alcohols and amino acid derivatives catalyzed by FDH coupling to enhance the regeneration capacity of NADH, reduce the regeneration cost of NADH, and achieve high efficiency and low cost.
Semi-rational hinge engineering: modulating the conformational transformation of glutamate dehydrogenase for enhanced reductive amination activity towards non-natural substrates
Liu, Yayun,Meng, Lijun,Wu, Jianping,Yang, Lirong,Yin, Xinjian,Zhou, Haisheng
, p. 3376 - 3386 (2020/06/09)
The active site is the common hotspot for rational and semi-rational enzyme activity engineering. However, the active site represents only a small portion of the whole enzyme. Identifying more hotspots other than the active site for enzyme activity engineering should aid in the development of biocatalysts with better catalytic performance. Glutamate dehydrogenases (GluDHs) are promising and environmentally benign biocatalysts for the synthesis of valuable chirall-amino acids by asymmetric reductive amination of α-keto acids. GluDHs contain an inter-domain hinge structure that facilitates dynamic reorientations of the domains relative to each other. Such hinge-bending conformational motions of GluDHs play an important role in regulating the catalytic activity. Thus, the hinge region represents a potential hotspot for catalytic activity engineering for GluDHs. Herein, we report semi-rational activity engineering of GluDHs with the hinge region as the hotspot. Mutants exhibiting significantly improved catalytic activity toward several non-natural substrates were identified and the highest activity increase reached 104-fold. Molecular dynamics simulations revealed that enhanced catalytic activity may arise from improving the open/closed conformational transformation efficiency of the protein with hinge engineering. In the batch production of three valuablel-amino acids, the mutants exhibited significantly improved catalytic efficiency, highlighting their industrial potential. Moreover, the catalytic activity of several active site tailored GluDHs was also increased by hinge engineering, indicating that hinge and active site engineering are compatible. The results show that the hinge region is a promising hotspot for activity engineering of GluDHs and provides a potent alternative for developing high-performance biocatalysts toward chirall-amino acid production.
Ultrasound-Controlled Chiral Separation of Four Amino Acids and 2,2,2-Trifluoro-1-(9-anthryl)ethanol
Lee, Jae Hwan,Ryoo, Jae Jeong
, p. 146 - 149 (2019/02/07)
Chiral separation of 4-hydroxyphenylglycine, phenylglycine, tryptophan, methionine, and 2,2,2-trifluoro-1-(9-anthryl)ethanol (TFAE) was performed under ultrasound reduction at room temperature and high temperature (50 °C). At high temperature (50 °C), both α and Rs were improved slightly under ultrasound reduction as compared to those under non-ultrasonic and ultrasonic irradiation (50 watt/L) conditions. Even at low temperatures, the largest α was observed under ultrasound reduction conditions, except in the case of methionine. However, at low temperature, Rs was reduced under ultrasound (50 watt/L) irradiation, but was improved under ultrasound reduction rather than under the continuous ultrasonic irradiation. Similar to the fact that gradient elution (based on solvent polarity) can improve α, ultrasound reduction can improve α and Rs. Ultrasound reduction is demonstrated to aid the rapid separation of chiral compounds with improved resolution, especially, at high temperatures. Although chromatographic separation using ultrasound has been rarely dealt with until now, ultrasound can be used as an external field in chromatography.
