10326-41-7Relevant articles and documents
Bridging racemic lactate esters with stereoselective polylactic acid using commercial lipase catalysis
Van Wouwe, Pieter,Dusselier, Michiel,Basic, Aurelie,Sels, Bert F.
, p. 2817 - 2824 (2013)
A productive and enantioselective hydrolysis of racemic mixtures of lactate esters with commercial Candida rugosa lipase was performed. This step contributes to a novel envisioned route for stereoselective PLA production by combining recent chemocatalytic developments with this biocatalytic contribution, foreseeing two separate l- and d-lactate enantiomer streams. A study of the hydrolysis kinetics identified an unexpected rate determining step at the origin of an unprecedented ester reactivity order.
Synthesis of (R)-lactic acid and (2R,5R)-2-tert-Butyl-5-methyl-1,3-dioxolan-4-one
Aitken, R. Alan,Meehan, Anna,Power, Lynn A.
, p. 1557 - 1559 (2015)
Abstract A convenient procedure for the synthesis of very expensive (R)-lactic acid from relatively inexpensive (R)-alanine is described. Its subsequent conversion into a chiral dioxolanone can be carried out by using an inexpensive pivalaldehyde-tert-butanol mixture.
Structures, chemotaxonomic significance, cytotoxic and Na+,K+-ATPase inhibitory activities of new cardenolides from Asclepias curassavica
Zhang, Rong-Rong,Tian, Hai-Yan,Tan, Ya-Fang,Chung, Tse-Yu,Sun, Xiao-Hui,Xia, Xue,Ye, Wen-Cai,Middleton, David A.,Fedosova, Natalya,Esmann, Mikael,Tzen, Jason T. C.,Jiang, Ren-Wang
, p. 8919 - 8929 (2014)
Five new cardenolide lactates (1-5) and one new dioxane double linked cardenolide glycoside (17) along with 15 known compounds (6-16 and 18-21) were isolated from the ornamental milkweed Asclepias curassavica. Their structures were elucidated by extensive spectroscopic methods (IR, UV, MS, 1D- and 2D-NMR). The molecular structures and absolute configurations of 1-3 and 17 were further confirmed by single-crystal X-ray diffraction analysis. Simultaneous isolation of dioxane double linked cardenolide glycosides (17-21) and cardenolide lactates (1-5) provided unique chemotaxonomic markers for this genus. Compounds 1-21 were evaluated for the inhibitory activities against DU145 prostate cancer cells. The dioxane double linked cardenolide glycosides showed the most potent cytotoxic effect followed by normal cardenolides and cardenolide lactates, while the C21 steroids were non-cytotoxic. Enzymatic assay established a correlation between the cytotoxic effects in DU145 cancer cells and the Ki for the inhibition of Na+,K+-ATPase. Molecular docking analysis revealed relatively strong H-bond interactions between the bottom of the binding cavity and compounds 18 or 20, and explained why the dioxane double linked cardenolide glycosides possessed higher inhibitory potency on Na+,K+-ATPase than the cardenolide lactate. This journal is
Enhancement of the catalytic activity of D-lactate dehydrogenase from Sporolactobacillus laevolacticus by site-directed mutagenesis
Nakano, Kento,Sawada, Shoichi,Yamada, Ryosuke,Mimitsuka, Takashi,Ogino, Hiroyasu
, p. 214 - 218 (2018)
Sporolactobacillus laevolacticus is a producer of D-lactic acid with high optical purity. The amino acid sequence of D-lactate dehydrogenase (D-LDH) from S. laevolacticus was compared with those of other lactate producers. To enhance the activity of D-LDH from S. laevolacticus, some amino acid residues close to the substrate binding site or the active center were replaced by site-directed mutagenesis. Ala234 of D-LDH from S. laevolacticus was found to be an important amino acid residue that positively affects catalytic activity. Site-saturation mutagenesis of the 234th residue was performed. The mutant D-LDH at the 234th residue from alanine to serine or glycine showed enhanced catalytic activity toward pyruvate. The kinetic analysis revealed that the kcat/Km of D-LDH_A234S and _A234G on pyruvate increased 1.9- and 1.2-fold, respectively. Furthermore, the double mutant D-LDH_T75L/A234S improved kcat/Km by 6.8-fold compared to that of wild-type D-LDH. These results showed the potential of the mutant D-LDH for microbial production of D-lactic acid by heterologous expression.
Use of wastewater sludge as a raw material for production of L-lactic acid
Nakasaki, Kiyohiko,Akakura, Naoki,Adachi, Tomohiko,Akiyama, Tetsuo
, p. 198 - 200 (1999)
This study utilizes wastewater sludges to produce L-lactic acid, a precursor of biodegradable plastic. The high concentrations of cellulose contained in the sludge, derived from a paper manufacturing facility, have been found to be convertible to L-lactic acid at a rate as high as 6.91 g/L. To achieve such a high conversion rate, the sludge must be pretreated with cellulase. This pretreatment includes inoculation of the sludge with lactic acid bacteria, strain LA1, after the sludge has been subjected to enzymatic hydrolysis. This study utilizes wastewater sludges to produce L-lactic acid, a precursor of biodegradable plastic. The high concentrations of cellulose contained in the sludge, derived from a paper manufacturing facility, have been found to be convertible to L-lactic acid at a rate as high as 6.91 g/L. To achieve such a high conversion rate, the sludge must be pretreated with cellulase. This pretreatment includes inoculation of the sludge with lactic acid bacteria, strain LA1, after the sludge has been subjected to enzymatic hydrolysis.
Reversible ketomethylene-based inhibitors of human neutrophil proteinase 3
Budnjo, Adnan,Narawane, Shailesh,Grauffel, Cédric,Schillinger, Anne-Sophie,Fossen, Torgils,Reuter, Nathalie,Haug, Bengt Erik
, p. 9396 - 9408 (2014)
Neutrophil serine proteases, proteinase 3 (PR3) and human neutrophil elastase (HNE), are considered as targets for chronic inflammatory diseases. Despite sharing high sequence similarity, the two enzymes have different substrate specificities and functions. While a plethora of HNE inhibitors exist, PR3 specific inhibitors are still in their infancy. We have designed ketomethylene-based inhibitors for PR3 that show low micromolar IC50 values. Their synthesis was made possible by amending a previously reported synthesis of ketomethylene dipeptide isosteres to allow for the preparation of derivatives suitable for solid phase peptide synthesis. The best inhibitor (Abz-VADnV[ψ](COCH2)ADYQ-EDDnp) was found to be selective for PR3 over HNE and to display a competitive and reversible inhibition mechanism. Molecular dynamics simulations show that the interactions between enzyme and ketomethylene-containing inhibitors are similar to those with the corresponding substrates. We also confirm that N- and C-terminal FRET groups are important for securing high inhibitory potency toward PR3.
Site-Specific, covalent immobilization of dehalogenase ST2570 catalyzed by formylglycine-generating enzymes and its application in batch and semi-continuous flow reactors
Jian, Hui,Wang, Yingwu,Bai, Yan,Li, Rong,Gao, Renjun
, (2016)
Formylglycine-generating enzymes can selectively recognize and oxidize cysteine residues within the sulfatase sub motif at the terminus of proteins to form aldehyde-bearing formylglycine (FGly) residues, and are normally used in protein labeling. In this study, an aldehyde tag was introduced to proteins using formylglycine-generating enzymes encoded by a reconstructed set of the pET28a plasmid system for enzyme immobilization. The haloacid dehalogenase ST2570 from Sulfolobus tokodaii was used as a model enzyme. The C-terminal aldehyde-tagged ST2570 (ST2570CQ) exhibited significant enzymological properties, such as new free aldehyde groups, a high level of protein expression and improved enzyme activity. SBA-15 has widely been used as an immobilization support for its large surface and excellent thermal and chemical stability. It was functionalized with amino groups by aminopropyltriethoxysilane. The C-terminal aldehyde-tagged ST2570 was immobilized to SBA-15 by covalent binding. The site-specific immobilization of ST2570 avoided the chemical denaturation that occurs in general covalent immobilization and resulted in better fastening compared to physical adsorption. The site-specific immobilized ST2570 showed 3-fold higher thermal stability, 1.2-fold higher catalytic ability and improved operational stability than free ST2570. The site-specific immobilized ST2570 retained 60% of its original activity after seven cycles of batch operation, and it was superior to the ST2570 immobilized to SBA-15 by physical adsorption, which loses 40% of its original activity when used for the second time. It is remarkable that the site-specific immobilized ST2570 still retained 100% of its original activity after 10 cycles of reuse in the semi-continuous flow reactor. Overall, these results provide support for the industrial-scale production and application of site-specific, covalently immobilized ST2570.
Affinity of a vancomycin polymer with bacterial surface models
Arimoto, Hirokazu,Oishi, Takehisa,Nishijima, Manabu,Kinumi, Tomoya
, p. 3347 - 3350 (2001)
The affinity between a vancomycin polymer (3) and cell wall intermediate mimics of vancomycin resistant bacteria (VRE) was determined by use of surface plasmon resonance (SPR). The increased affinity of 3 over monomeric vancomycin derivatives 1 and 2 suggests the importance of tighter binding to VRE surfaces in the enhanced antibacterial activities of 3.
Development of a Novel Biocatalyst for the Resolution of rac-Pantolactone
Kesseler, Maria,Friedrich, Thomas,Hoeffken, Hans Wolfgang,Hauer, Bernhard
, p. 1103 - 1110 (2002)
A novel L-pantolactone hydrolase, Lph, from Agrobacterium tumefaciens Lu681 was characterized, which stereospecifically hydrolyses L-pantolactone to L-pantoic acid yielding D-pantolactone with > 95% enantiomeric excess. The enzyme was found to be a 30 kDa-Zn2+-hydrolase with a Km for L-pantolactone of 7 mM and a Vmax of 30 U/mg. The corresponding lph gene was identified as an 807 bp ORF and cloned into E. coli. It was overexpressed under control of Ptac and Prha yielding enzyme activities of up to 600 U/g dry weight. Resolution of D,L-pantolactone in repeated batches with isolated Lph and enzyme recovery by membrane filtration gave D-pantolactone with 50% yield and 90-95% ee over 6 days. Covalent immobilization to EupergitC led to a stable biocatalyst easy to handle in a repeated batch production of D-pantolactone. Further improvements in the activity of Lph were achieved by directed evolution of the enzyme. Activities of mutants F62S, K197D and F100L were increased 2.3, 1.7, and 1.5 fold, respectively.
D-(-)-Lactic acid production from cellobiose and cellulose by Lactobacillus lactis mutant RM2-24
Singhvi, Mamta,Joshi, Dipti,Adsul, Mukund,Varma, Anjani,Gokhale, Digambar
, p. 1106 - 1109 (2010)
Lactobacillus lactis mutant RM2-24 utilizes cellobiose efficiently, converting it into d-(-)-lactic acid. Cellobiose-degrading enzyme activities were determined for whole cells, cell extracts and disrupted cells. Aryl-β-glucosidase activity was detected in whole cells and disrupted cells, suggesting that these activities are confined to the cells. The mutant produced 80 g l-1 of lactic acid from 100 g l-1 of cellobiose with 1.66 g l-1 h-1 productivity. Production of d-lactic acid from different cellulose samples was also studied. The cellulose samples at high concentration (10%) were hydrolyzed by cellulase enzyme preparation (10 FPU g-1 cellulose) derived from Penicillium janthinellum mutant EU1 generated in our own laboratory. We obtained a maximum 72% hydrolysis, yielding glucose and cellobiose as the main end products. Lactic acid was produced from these cellulose samples by simultaneous saccharification and fermentation (SSF) in a media containing a cellulase enzyme preparation derived from Penicillium janthinellum mutant EU1 and cellobiose utilizing Lactobacillus lactis mutant RM2-24. A maximum lactic acid concentration of 73 g l-1 was produced from a concentration of 100 g l-1 of bagasse-derived cellulose, the highest productivity and yield being 1.52 g l-1 h-1 and 0.73 g g-1, respectively. Considering that bagasse is a waste material available in abundance, we propose to use this biomass to produce cellulose and then sugars, which can be fermented to valuable products such as ethanol and lactic acid.
