7326-19-4Relevant articles and documents
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.
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 (2019/03/11)
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.
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.
An Atropos Biphenyl Bisphosphine Ligand with 2,2′-tert-Butylmethylphosphino Groups for the Rhodium-Catalyzed Asymmetric Hydrogenation of Enol Esters
Jia, Jia,Fan, Dongyang,Zhang, Jian,Zhang, Zhenfeng,Zhang, Wanbin
, p. 3793 - 3800 (2018/09/20)
This is an update of our previous work concerning the development of Atropos biphenyl bisphosphine ligands. An unexpected Atropos structural property was confirmed by single crystal X-ray diffraction and this result is consistent with the computational calculations described in our previous work. This P-stereogenic bisphosphine ligand possessing a biphenyl backbone and 2,2′-tert-butylmethylphosphino groups has been applied to the Rh-catalyzed asymmetric hydrogenation of enol esters, which has not been widely studied and can be used for the synthesis of several important bioactive compounds. Although there is room for further improvement in enantioselectivity, the results reported herein provide a further understanding of such types of ligands. (Figure presented.).
Preparation method of chiral phenyllactic acid
-
, (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.
Investigating Substrate Scope and Enantioselectivity of a Defluorinase by a Stereochemical Probe
Wang, Jian-Bo,Ilie, Adriana,Yuan, Shuguang,Reetz, Manfred T.
, p. 11241 - 11247 (2017/08/21)
The possibility of a double Walden inversion mechanism of the fluoracetate dehalogenase FAcD (RPA1163) has been studied by subjecting rac-2-fluoro-2-phenyl acetic acid to the defluorination process. This stereochemical probe led to inversion of configuration in a kinetic resolution with an extremely high selectivity factor (E > 500), showing that the classical mechanism involving SN2 reaction by Asp110 pertains. The high preference for the (S)-substrate is of synthetic value. Wide substrate scope of RPA1163 in such hydrolytic kinetic resolutions can be expected because the reaction of the even more sterically demanding rac-2-fluoro-2-benzyl acetic acid proceeded similarly. Substrate acceptance and stereoselectivity were explained by extensive molecular modeling (MM) and molecular dynamics (MD) computations. These computations were also applied to fluoroacetic acid itself, leading to further insights.
Solvent-induced chirality switching in the enantioseparation of regioisomeric hydroxyphenylpropionic acids via diastereomeric salt formation with (1R,2S)-2-amino-1,2-diphenylethanol
Kodama, Koichi,Nagata, Jun,Kurozumi, Nobuhiro,Shitara, Hiroaki,Hirose, Takuji
supporting information, p. 460 - 466 (2017/03/23)
The enantioseparation of three hydroxyphenylpropionic acid isomers via diastereomeric salt formation with (1R,2S)-2-amino-1,2-diphenylethanol has been demonstrated. The racemates of all three acid isomers were successfully separated with high efficiency (0.56–0.84) after single crystallization. For 2-hydroxy-3-phenylpropionic acid 4, the configuration of the less-soluble salt was controlled by the crystallization solvent: the (R)-4 salt was crystallized from water, while 2-propanol afforded the (S)-4 salt. The chiral recognition mechanism of the three acids was discussed based on the crystal structures of the diastereomeric salts.
