156-05-8Relevant academic research and scientific papers
Quantitative transformation of racemic 2-hydroxy acids into (R)-2-hydroxy acids by enantioselective oxidation with glycolate oxidase and subsequent reduction of 2-keto acids with D-lactate dehydrogenase
Adam, Waldemar,Lazarus, Michael,Saha-Moeller, Chantu R.,Schreier, Peter
, p. 351 - 355 (1998)
The enzymatic resolution of chiral 2-hydroxy acids 1 by enantioselective oxidation with molecular oxygen in the presence of glycolate oxidase from spinach (Spinacia oleracea) and subsequent asymmetric reduction of 2-oxo acids 2 with D-lactate dehydrogenase from Lactobacillus leichmannii leads to enantiomerically pure (R)-2-hydroxy acids in up to 89% yield based on the racemate.
Chiral separation of phenyllactic acid by helical structure from spring dextrin
Xu, Jin,Xu, Xueming,Wang, Qiang,Fan, Xuerong
, p. 515 - 521 (2015)
We performed the enzymatic synthesis of spring dextrin (SD) with a helical conformation and investigated its chiral-recognition properties in relation to the stereoselective phenyllactic acid (PLA), using reversed-phase high-performance liquid chromatography. The effects of column temperature, buffer pH and methanol content on enantioselective separation were investigated. Baseline chromatographic separation was achieved on an Inertsil ODS-SP column using 1 % SD as the chiral mobile-phase additive. Helical structure was necessary for chiral separation of PLA, according to visible spectroscopy. Molecular dynamic simulations to predict the interactions between SD and PLA showed that van der Waals attractions played an important role in enantiomer separation.
A novel D-2-hydroxy acid dehydrogenase with high substrate preference for phenylpyruvate originating from lactic acid bacteria: Structural analysis on the substrate specificity
Lee, Hoe-Suk,Park, Jisu,Yoo, Young Je,Yeon, Young Joo
, p. 37 - 44 (2019)
2-Hydroxy acid dehydrogenases (2-HADHs) have been implicated in the synthesis of 2-hydroxy acids from 2-oxo acids that are used in wide areas of industry. D-lactate dehydrogenases (D-LDHs), a subfamily of 2-HADH, have been utilized to this purpose, yet they exhibited relatively low catalytic activity to the 2-oxo acids with large functional groups at C3. In this report, four putative 2-HADHs from Oenococcus oeni, Weissella confusa, Weissella koreensis and Pediococcus claussenii were examined for activity on phenylpyruvate (PPA), a substrate to 3-phenyllactic acid (PLA) with a C3 phenyl group. The 2-HADH from P. claussenii was found to have the highest kcat/Km on PPA with 1,348.03 s?1 mM?1 among the four enzymes with higher substrate preference for PPA than pyruvate. Sequential, structural and mutational analysis of the enzyme revealed that it belonged to the D-LDH family, and phenylalanine at the position 51 was the key residue for the PPA binding to the active site via hydrophobic interaction, whereas in the 2-HADHs from O. oeni and W. confusa the hydrophilic tyrosine undermined the interaction. Because phenyllactate is a potential precursor for pharmaceutical compounds, antibiotics and biopolymers, the enzyme could increase the efficiency of bio-production of valuable chemicals. This study suggests a structural basis for the high substrate preference of the 2-HADH, and further engineering possibilities to synthesize versatile 2-hydroxy acids.
Conversion of a Cyanhydrin Compound into S-( - )-3-Phenyllactic Acid by Enantioselective Hydrolytic Activity of Pseudomonas sp. BC-18
Hashimoto, Yoshihiro,Kobayashi, Etsuko,Endo, Takakazu,Nishiyama, Makoto,Horinouchi, Sueharu
, p. 1279 - 1283 (1996)
A Pseudomonas strain, named BC-18, which can convert racemic phenylacetaldehyde-cyanhydrin (3-phenyllactonitrile) enantioselectively to S-( - )-3-phenyllactic acid (S-PLA), was isolated from soil. Although PLA produced with intact cells contained the S enantiomers of approximately 75% enantiomeric excess (% e.e.), repeated crystallization gave a higher purity (99.8% e.e.) of the S configuration product. Production of S-PLA was significantly increased when 2.0% (w/v) of calcium chloride were added to the reaction mixture for precipitation of S-PLA. Chemical mutagenesis yielded a mutant strain, named BC348-9, with 16 times higher activity (40mU/OD630), compared with that of the parent strain (2.5mU/OD630). When the mutant strain BC348-9 was used, approximately 18g/OD630 was produced, which is 12 times higher than that of the parent strain. The final accumulation of PLA exceeded 6.0%, 1.2 times higher than that of the parent strain.
Trikoveramides A-C, cyclic depsipeptides from the marine cyanobacterium Symploca hydnoides
Goh, Jun Xian,Katermeran, Nursheena Parveen,Phyo, Ma Yadanar,Tan, Lik Tong
, (2021/07/17)
Trikoveramides A – C, members of the kulolide superfamily of cyclic depsipeptides, were isolated from the marine cyanobacterium, Symploca hydnoides, collected from Bintan Island, Indonesia. Their planar structures were elucidated by a combination of NMR spectroscopy and HRMS spectral data. The absolute configurations of the amino acid and phenyllactic acid units were confirmed by Marfey's and chiral HPLC analyses, respectively, while the relative stereochemistry of the 3-hydroxy-2-methyl-7-octynoic acid (Hmoya) unit in trikoveramide A was elucidated by the application of the J-based configuration analysis and NOE correlations. The cytotoxic activity of the trikoveramides were evaluated against MOLT-4 human leukemia cells and gave IC50 values of 9.3 μM, 35.6 μM and 48.8 μM for trikoveramide B, trikoveramide C and trikoveramide A, respectively. In addition, trikoveramides A – C showed weak to moderate inhibition in the quorum sensing inhibitory assay based on the Pseudomonas aeruginosa lasB-gfp and rhlA-gfp bioreporter strains.
Semirational Design of Fluoroacetate Dehalogenase RPA1163 for Kinetic Resolution of α-Fluorocarboxylic Acids on a Gram Scale
Chen, Bo,Li, Min,Li, Yanwei,Ma, Ming,Tian, Shaixiao,Tong, Wei,Wang, Jian-Bo,Xu, Guangyu,Yue, Yue,Zhang, Hongxia
, p. 3143 - 3151 (2020/03/23)
Here the synthetic utility of fluoroacetate dehalogenase RPA1163 is explored for the production of enantiomerically pure (R)-α-fluorocarboxylic acids and (R)-α-hydroxylcarboxylic acids via kinetic resolution of racemic α-fluorocarboxylic acids. While wild-type (WT) RPA1163 shows high thermostability and fairly wide substrate scope, many interesting yet poorly or moderately accepted substrates exist. In order to solve this problem and to develop upscaled production, in silico calculations and semirational mutagenesis were employed. Residue W185 was engineered to alanine, serine, threonine, or asparagine. The two best mutants, W185N and W185T, showed significantly improved performance in the reactions of these substrates, while in silico calculations shed light on the origin of these improvements. Finally, 10 α-fluorocarboxylic acids and 10 α-hydroxycarboxylic acids were prepared on a gram scale via kinetic resolution enabled by WT, W185T, or W185N. This work expands the biocatalytic toolbox and allows a deep insight into the fluoroacetate dehalogenase catalyzed C-F cleavage mechanism.
Glycerol conversion to high-value chemicals: The implication of unnatural α-amino acid syntheses using natural resources
Park, Yun Ji,Yang, Jung Woon
, p. 2615 - 2620 (2019/06/03)
Glycerol derivatives are an important class of compounds, which have great applications as basic structural building blocks in organic synthesis. O-Benzylglycerol was oxidised to produce a high-value compound in high yield using a NaOtBu-O2 system. Furthermore, the synthetic utility of the resulting product was demonstrated by its transformation into unnatural α-amino acids, thus showing the valorisation of glycerol biomass.
Heterologous production of asperipin-2a: Proposal for sequential oxidative macrocyclization by a fungi-specific DUF3328 oxidase
Ye, Ying,Ozaki, Taro,Umemura, Myco,Liu, Chengwei,Minami, Atsushi,Oikawa, Hideaki
supporting information, p. 39 - 43 (2019/01/04)
Asperipin-2a is a ribosomally synthesized and post-translationally modified peptide isolated from Asperigillus flavus. Herein, we report the heterologous production of asperipin-2a and determination of its absolute structure. Notably, the characteristic bicyclic structure was likely constructed by a single oxidase containing the DUF3328 domain.
Highly Efficient Deracemization of Racemic 2-Hydroxy Acids in a Three-Enzyme Co-Expression System Using a Novel Ketoacid Reductase
Xue, Ya-Ping,Wang, Chuang,Wang, Di-Chen,Liu, Zhi-Qiang,Zheng, Yu-Guo
, p. 1 - 13 (2018/04/26)
Enantiopure 2-hydroxy acids (2-HAs) are important intermediates for the synthesis of pharmaceuticals and fine chemicals. Deracemization of racemic 2-HAs into the corresponding single enantiomers represents an economical and highly efficient approach for synthesizing chiral 2-HAs in industry. In this work, a novel ketoacid reductase from Leuconostoc lactis (LlKAR) with higher activity and substrate tolerance towards aromatic α-ketoacids was discovered by genome mining, and then its enzymatic properties were characterized. Accordingly, an engineered Escherichia coli (HADH-LlKAR-GDH) co-expressing 2-hydroxyacid dehydrogenase, LlKAR, and glucose dehydrogenase was constructed for efficient deracemization of racemic 2-HAs. Most of the racemic 2-HAs were deracemized to their (R)-isomers at high yields and enantiomeric purity. In the case of racemic 2-chloromandelic acid, as much as 300 mM of substrate was completely transformed into the optically pure (R)-2-chloromandelic acid (> 99% enantiomeric excess) with a high productivity of 83.8 g L?1 day?1 without addition of exogenous cofactor, which make this novel whole-cell biocatalyst more promising and competitive in practical application.
Preparation method of chiral phenyllactic acid
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, (2018/09/29)
The invention relates to a preparation method of chiral phenyllactic acid. The preparation method comprises the steps: salifying (S)-phenethylamine serving as a resolving agent and DL-phenyllactic acid in a specific solvent, and carrying out recrystallization to obtain (S)-phenethylamine-D-phenyl lactate; salifying (R)-phenethylamine serving as a resolving agent and DL-phenyllactic acid in a specific solvent, and carrying out recrystallization to obtain (R)-phenethylamine-L-phenyl lactate; and carrying out acid dissociation to prepare the chiral phenyllactic acid. Compared with the prior art,the preparation method has the advantages that the adopted resolving agent is cheap, available and easy to recover, and the preparation method is suitable for industrial production.
