1. Diaminopelargonic acid transaminase from psychrobacter cryohalolentis is active towards (s)-(-)-1-phenylethylamine, Aldehydes and α-diketones.
Tatiana N Stekhanova, Ekaterina Yu Bezsudnova, Vladimir O Popov, Konstantin M Boyko, Anna V Popinako, Tatiana V Rakitina, Alena Yu Nikolaeva. Appl Microbiol Biotechnol. 2018 Nov; 102(22): 9621-9633. DOI: 10.1007/s00253-018-9310-0. PMID: 30178202.
Substrate and reaction promiscuity is a remarkable property of some enzymes and facilitates the adaptation to new metabolic demands in the evolutionary process. Substrate promiscuity is also a basis for protein engineering for biocatalysis. However, molecular principles of enzyme promiscuity are not well understood. Even for the widely studied PLP-dependent transaminases of class III, the reliable prediction of the biocatalytically important amine transaminase activity is still difficult if the desired activity is unrelated to the natural activity. Here, we show that 7,8-diaminopelargonic acid transaminase (synthase), previously considered to be highly specific, is able to convert (S)-(-)-1-phenylethylamine and a number of aldehydes and diketones. We were able to characterize the (S)-amine transaminase activity of 7,8-diaminopelargonic acid transaminase from Psychrobacter cryohalolentis (Pcryo361) and analyzed the three-dimensional structure of the enzyme. New substrate specificity for α-diketones was observed, though only a weak activity towards pyruvate was found. We examined the organization of the active site and binding modes of S-adenosyl-L-methionine and (S)-(-)-1-phenylethylamine using X-ray analysis and molecular docking. We suggest that the Pcryo361 affinity towards (S)-(-)-1-phenylethylamine arises from the recognition of the hydrophobic parts of the specific substrates, S-adenosyl-L-methionine and 7-keto-8-aminopelargonic acid, and from the flexibility of the active site. Our results support the observation that the conversion of amines is a promiscuous activity of many transaminases of class III and is independent from their natural function. The analysis of amine transaminase activity from among various transaminases will help to make the sequence-function prediction for biocatalysis more reliable.
2. Synthesis, Characterization, And dft studies of a new chiral ionic liquid from (s)-1-phenylethylamine.
Xiaoli Hu, Tao Wang, Shuya Cui. Spectrochim Acta A Mol Biomol Spectrosc. 2014 Dec 10; 133: 778-84. DOI: 10.1016/j.saa.2014.06.057. PMID: 25000565.
A new chiral ionic liquid was synthesized from (S)-1-phenylethylamine and it was studied by IR, Raman, polarimetry, NMR and X-ray crystal diffraction. Its vibrational spectral bands are precisely ascribed to the studied structure with the aid of DFT theoretical calculations. The optimized geometries and calculated vibrational frequencies are evaluated via comparison with experimental values. The vibrational spectral data obtained from IR and Raman spectra are assigned based on the results of the theoretical calculations by the DFT-B3LYP method at 6-311G(d,p) level. The computed vibrational frequencies were scaled by scale factors to yield a good agreement with observed experimental vibrational frequencies.The vibrational modes assignments were performed by using the animation option of GaussView5.0 graphical interface for Gaussian program.
3. Construction of a chiral central nervous system (cns)-active aminotetralin drug compound based on a synthesis strategy using multitasking properties of (s)-1-phenylethylamine.
Fredrik R Qvarnström, Hans-Jürgen Federsel, Martin Hedberg, Magnus P T Sjögren, Wei Tian. Acc Chem Res. 2007 Dec; 40(12): 1377-84. DOI: 10.1021/ar700102c. PMID: 17668920.
This Account describes the design and development of a scalable synthesis for the drug molecule AR-A2 (1) starting from the discovery route originating in medicinal chemistry. Special emphasis is placed on the introduction of the correct (R) stereochemistry on C2, which was ultimately achieved in a diastereoselective imine-reducing step applying NaBH4. After optimization, this transformation was operated on a large pilot-plant scale (2000 L), offering the desired product (11) in 55% yield and 96% diastereomeric excess at a 100 kg batch size. From a synthesis strategy point of view, the choice of (S)-1-phenylethylamine (9) was crucial not only for its role as a provider of the NH2 functionality and the stereo-directing abilities but also as an excellent protecting group in the subsequent N-arylation reaction, according to the Buchwald-Hartwig protocol. As one of the very first examples in its kind, the latter step was scaled up to pilot manufacturing (125 kg in 2500 L vessel size), delivering an outstanding isolated yield of 95%. This consecutive series of chemical transformations was completed with an environmentally friendly removal of the phenethyl appendage. In addition, an elegant method to synthesize the tetralone substrate 6, as well as a novel and robust procedure to use imidazole as a buffer for the selective formation of the mono-HBr salt of AR-A2, will be briefly described.
