828-01-3Relevant articles and documents
Purification and partial characterization of Lactobacillus species SK007 lactate dehydrogenase (LDH) catalyzing phenylpyruvic acid (PPA) conversion into phenyllactic acid (PLA)
Li, Xingfeng,Jiang, Bo,Pan, Beilei,Mu, Wanmeng,Zhang, Tao
, p. 2392 - 2399 (2008)
Phenyllactic acid (PLA) is a novel antimicrobial compound synthesized by lactic acid bacteria (LAB), and its production from phenylpyruvic acid (PPA) is an effective approach. In this work, a lactate dehydrogenase (LDH), which catalyzes the reduction of PPA to PLA, has been purified to homogeneity from a cell-free extract of Lactobacillus sp. SK007 by precipitation with ammonium sulfate, ion exchange, and gel filtration chromatography. The purified enzyme had a dimeric form with a molecular mass of 78 kDa (size exclusion chromatography) or 39 kDa (SDS-PAGE). The ratio of enzyme activity with PPA to that with pyruvate being almost invariable at every purification step indicated that, in Lactobacillus sp. SK007, LDH is responsible for the conversion of PPA into PLA. HPLC profiles of PPA transformation into PLA by growing cells, cell-free extract, and purified LDH of Lactobacillus sp. SK007 were also investigated. Results showed that the presence of NADH was found to be necessary for the enzymatic production of PLA from PPA. The purified LDH displayed optimal activity for PPA at pH 6.0 and 40°C. The Km values of the enzyme for PPA and pyruvate were 1.69 and 0.32 mM, respectively. Moreover, because other screened LAB strains exhibiting relatively high LDH activity toward PPA produced also considerable amounts of PLA, LDH activity for PPA could be therefore used as a screening marker for PLA-producing LAB.
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.
Oxalyl-CoA Decarboxylase Enables Nucleophilic One-Carbon Extension of Aldehydes to Chiral α-Hydroxy Acids
Burgener, Simon,Cortina, Ni?a Socorro,Erb, Tobias J.
supporting information, p. 5526 - 5530 (2020/02/20)
The synthesis of complex molecules from simple, renewable carbon units is the goal of a sustainable economy. Here we explored the biocatalytic potential of the thiamine-diphosphate-dependent (ThDP) oxalyl-CoA decarboxylase (OXC)/2-hydroxyacyl-CoA lyase (HACL) superfamily that naturally catalyzes the shortening of acyl-CoA thioester substrates through the release of the C1-unit formyl-CoA. We show that the OXC/HACL superfamily contains promiscuous members that can be reversed to perform nucleophilic C1-extensions of various aldehydes to yield the corresponding 2-hydroxyacyl-CoA thioesters. We improved the catalytic properties of Methylorubrum extorquens OXC by rational enzyme engineering and combined it with two newly described enzymes—a specific oxalyl-CoA synthetase and a 2-hydroxyacyl-CoA thioesterase. This enzymatic cascade enabled continuous conversion of oxalate and aromatic aldehydes into valuable (S)-α-hydroxy acids with enantiomeric excess up to 99 %.
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.
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.
Controllable Intramolecular Unactivated C(sp3)-H Amination and Oxygenation of Carbamates
Guo, Qihang,Ren, Xiang,Lu, Zhan
supporting information, p. 880 - 884 (2019/05/16)
Dual catalyst-controlled intramolecular unactivated C(sp3)-H amination and oxygenation of carbamates merging visible-light photocatalysis and earth-abundant transition metal catalysis have been reported. Useful amino alcohol and diol derivatives could be selectively obtained from readily available tertiary alcohol derivatives. The possible mechanisms have been proposed via a 1,5-HAT process followed by Lewis acid-controlled cyclization. The nickel and zinc catalysts inhibit the formation of oxygenation and amination products, respectively. An interesting phenomenon of chirality transfer is also observed.
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.
Preparative Asymmetric Synthesis of Canonical and Non-canonical α-amino Acids Through Formal Enantioselective Biocatalytic Amination of Carboxylic Acids
Dennig, Alexander,Blaschke, Fabio,Gandomkar, Somayyeh,Tassano, Erika,Nidetzky, Bernd
supporting information, (2019/02/09)
Chemical and biocatalytic synthesis of non-canonical α-amino acids (ncAAs) from renewable feedstocks and using mild reaction conditions has not efficiently been solved. Here, we show the development of a three-step, scalable and modular one-pot biocascade for linear conversion of renewable fatty acids (FAs) into enantiopure l-α-amino acids. In module 1, selective α-hydroxylation of FAs is catalyzed by the P450 peroxygenase P450CLA. By using an automated H2O2 supplementation system, efficient conversion (46 to >99%; TTN>3300) of a broad range of FAs (C6:0 to C16:0) into valuable α-hydroxy acids (α-HAs; >90% α-selective) is shown on preparative scale (up to 2.3 g L?1 isolated product). In module 2, a redox-neutral hydrogen borrowing cascade (alcohol dehydrogenase/amino acid dehydrogenase) allowed further conversion of α-HAs into l-α-AAs (20 to 99%). Enantiopure l-α-AAs (e.e. >99%) including the pharma synthon l-homo-phenylalanine can be obtained at product titers of up to 2.5 g L?1. Based on renewables and excellent atom economy, this biocascade is among the shortest and greenest synthetic routes to structurally diverse and industrially relevant ncAAs. (Figure presented.).
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.
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.
