scholarly journals Production of a Human Metabolite of Atorvastatin by Bacterial CYP102A1 Peroxygenase

2021 ◽  
Vol 11 (2) ◽  
pp. 603
Author(s):  
Thi Huong Ha Nguyen ◽  
Soo-Jin Yeom ◽  
Chul-Ho Yun

Atorvastatin is a widely used statin drug that prevents cardiovascular disease and treats hyperlipidemia. The major metabolites in humans are 2-OH and 4-OH atorvastatin, which are active metabolites known to show highly inhibiting effects on 3-hydroxy-3-methylglutaryl-CoA reductase activity. Producing the hydroxylated metabolites by biocatalysts using enzymes and whole-cell biotransformation is more desirable than chemical synthesis. It is more eco-friendly and can increase the yield of desired products. In this study, we have found an enzymatic strategy of P450 enzymes for highly efficient synthesis of the 4-OH atorvastatin, which is an expensive commercial product, by using bacterial CYP102A1 peroxygenase activity with hydrogen peroxide without NADPH. We obtained a set of CYP102A1 mutants with high catalytic activity toward atorvastatin using enzyme library generation, high-throughput screening of highly active mutants, and enzymatic characterization of the mutants. In the hydrogen peroxide supported reactions, a mutant, with nine changed amino acid residues compared to a wild-type among tested mutants, showed the highest catalytic activity of atorvastatin 4-hydroxylation (1.8 min−1). This result shows that CYP102A1 can catalyze atorvastatin 4-hydroxylation by peroxide-dependent oxidation with high catalytic activity. The advantages of CYP102A1 peroxygenase activity over NADPH-supported monooxygenase activity are discussed. Taken together, we suggest that the P450 peroxygenase activity can be used to produce drugs’ metabolites for further studies of their efficacy and safety.

2021 ◽  
Author(s):  
Ruixue Wang ◽  
Ying Yue ◽  
Huiying Wei ◽  
Jinxin Guo ◽  
Yanzhao Yang

Here, a novel synthetic route of ceria-based nanocatalysts with high catalytic activity and excellent stability was constructed by utilizing function groups from surface ligands. The surface of ceria nanorods were...


2014 ◽  
Vol 69 (5) ◽  
Author(s):  
Mukhamad Nurhadi ◽  
Jon Efendi ◽  
Lee Siew Ling ◽  
Teuku Meurah Indra Mahlia ◽  
Ho Chin Siong ◽  
...  

Titanium dioxide supported sulfonated low rank coal catalyst possesses high catalytic activity in liquid phase oxidation of styrene with aqueous hydrogen peroxide at room temperature. The catalysts were prepared by sulfonation with concentrated sulfuric acid and impregnation of titanium dioxide (500-2500 µmol). The effect of titanium dioxide impregnation and calcinations on the catalysts were studied by X-ray diffraction, UV-vis diffuse reflectance spectroscopy, Fourier transform infrared spectroscopy, BET surface area, field emission scanning electron microscopy and hydrophobicity measurement. The catalytic activity of the catalysts in the oxidation of styrene by aqueous H2O2 without calcination increased when the amount of titanium dioxide increased. Meanwhile, the catalytic activity of the catalyst calcined at 500oC for 2 h was lower than before calcination. It is suggested that the agglomeration of titanium dioxide and hydrophobicity play important role in the catalytic activity of titanium dioxide-supported sulfonated low rank coal in the oxidation of styrene with aqueous H2O2. 


Catalysts ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1078
Author(s):  
Hang Zhang ◽  
Zhipeng Ma ◽  
Yunpeng Min ◽  
Huiru Wang ◽  
Ru Zhang ◽  
...  

Several kinds of composite materials with phosphotungstic acid (PTA) as the catalyst were prepared with activated carbon as support, and their structures were characterized. According to the Box–Behnken central combination principle, the mathematical model of the heterogeneous system is established. Based on the single-factor experiments, the reaction temperature, the reaction time, the amount of hydrogen peroxide and the loading capacity of PTA were selected as the influencing factors to study the catalyzed oxidation of hydrogen peroxide and degradation of high molecular weight chitosan. The results of IR showed that the catalyst had a Keggin structure. The results of the mercury intrusion test showed that the pore structure of the supported PTA catalyst did not change significantly, and with the increase of PTA loading, the porosity and pore volume decreased regularly, which indicated that PTA molecules had been absorbed and filled into the pore of activated carbon. The results of Response Surface Design (RSD) showed that the optimum reaction conditions of supported PTA catalysts for oxidative degradation of high molecular weight chitosan by hydrogen peroxide were as follows: reaction temperature was 70 ℃, reaction time was 3.0 h, the ratio of hydrogen peroxide to chitosan was 2.4 and the catalyst loading was 30%. Under these conditions, the yield and molecular weight of water-soluble chitosan were 62.8% and 1290 Da, respectively. The supported PTA catalyst maintained high catalytic activity after three reuses, which indicated that the supported PTA catalyst had excellent catalytic activity and stable performance compared with the PTA catalyst.


1997 ◽  
Vol 324 (2) ◽  
pp. 619-626 ◽  
Author(s):  
Javier PEÑA-DÍAZ ◽  
Andrea MONTALVETTI ◽  
Ana CAMACHO ◽  
Claribel GALLEGO ◽  
Luis M. RUIZ-PEREZ ◽  
...  

We report the isolation and characterization of a genomic clone containing the open reading frame sequence for 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase from Trypanosoma cruzi, the causative agent of Chagas' disease. The protozoan gene encoded for a smaller polypeptide than the rest of the genes described from eukaryotic organisms and the deduced amino acid sequence could be aligned with the C-terminal half of animal and plant reductases exhibiting pronounced similarity to other eukaryotic counterparts. Further examination of the 5′ flanking region by cDNA analysis and establishment of the splice acceptor sites clearly indicated that the corresponding mRNA apparently lacks sequences encoding a membrane N-terminal domain. The reductase gene is a single copy and is located on a chromosome of 1.36 Mb as determined by contour-clamped homogeneous electric field electrophoresis. The overall cellular distribution of enzymic activity was investigated after differential centrifugation of Trypanosoma cell extracts. Reductase activity was primarily associated with the cellular soluble fraction because 95% of the total cellular activity was recovered in the supernatant and was particularly sensitive to proteolytic inactivation. Furthermore the enzyme can be efficiently overexpressed in a highly active form by using the expression vector pET-11c. Thus Trypanosoma cruziHMG-CoA reductase is unique in the sense that it totally lacks the membrane-spanning sequences present in all eukaryotic HMG-CoA reductases so far characterized.


RSC Advances ◽  
2014 ◽  
Vol 4 (100) ◽  
pp. 57185-57191 ◽  
Author(s):  
Baowei Wang ◽  
Sihan Liu ◽  
Zongyuan Hu ◽  
Zhenhua Li ◽  
Xinbin Ma

Co3O4 nanoparticles showed high catalytic activity for low temperature CO methanation. CoO is the active phase of the catalyst. Pre-reduction treatment can improve catalytic stability.


2013 ◽  
Vol 46 (5) ◽  
pp. 1353-1360 ◽  
Author(s):  
Sylvio Haas ◽  
Robert Fenger ◽  
Edoardo Fertitta ◽  
Klaus Rademann

Recently, a so-called `crown-jewel' concept of preparation of Au/Pd-based colloidal nanoclusters has been reported [Zhang, Watanabe, Okumura, Haruta & Toshima (2011).Nat. Mater.11, 49–52]. Here, a different way of preparing highly active Au/Pd-based nanoclusters is presented. The origin of the increased activity of Au/Pd-based colloidal bimetallic nanoclusters was unclear up to now. However, it is, in general, accepted that in the nanometre range (1–100 nm) the cluster size, shape and composition affect the structural characteristics (e.g.lattice symmetry, unit cell), electronic properties (e.g.band gap) and chemical properties (e.g.catalytic activity) of a material. Hence, a detailed study of the relationship between the nanostructure of nanoclusters and their catalytic activity is presented here. The results indicate that a high surface-to-volume ratio of the nanoclusters combined with the presence of `both' Au and Pd isolated regions at the surface are crucial to achieve a high catalytic activity. A detailed structure elucidation directly leads to a mechanistic proposal, which indeed explains the higher catalytic activity of Au/Pd-based catalysts compared with pure metallic Au or Pd. The mechanism is based on cascade catalysis induced by a single type of nanoparticle with an intermixed surface of Au and Pd.


Author(s):  
Nor Masdiana Zulkeple ◽  
Norhasyimah Mohd Kamal ◽  
Jamilah Mohd Ekhsan ◽  
Salasiah Che Me ◽  
Swee Ean Lim ◽  
...  

A series of sulphate-vanadia impregnated fumed silica oxidative catalysts were synthesized via impregnation method. The samples were prepared by impregnation of 1 wt% of vanadium and 0.2 M of sulphuric acid onto fumed silica as support. Surface area of the silica supported samples were similar of 118 m2/g. UV-Vis DRS results showed existence of o supported V species and the charge transfer bands associated with O2- to V5+ in tetrahedral environments. Catalytic performance were evaluated via epoxidation of 1-octene to 1,2-epoxyoctane using hydrogen peroxide as an oxidant. It had been demonstrated that sulphate-vanadia impregnated fumed silica had high catalytic activity of 626 ± 0.2 mmol epoxide was produced after 24 h reaction. This may indicate that more oxidative sites were generated after the impregnation of V and sulphate onto the SiO2 matrixes.


Author(s):  
Mukhamad Nurhadi

<p>The modified coal char from low-rank coal by sulfonation, titanium impregnation and followed by alkyl silylation possesses high catalytic activity in styrene oxidation. The surface of coal char was undergone several steps as such: modification using concentrated sulfuric acid in the sulfonation process, impregnation of 500 mmol titanium(IV) isopropoxide and followed by alkyl silylation of n-octadecyltriclorosilane (OTS). The catalysts were characterized by X-ray diffraction (XRD), IR spectroscopy, nitrogen adsorption, and hydrophobicity. The catalytic activity of the catalysts has been examined in the liquid phase styrene oxidation by using aqueous hydrogen peroxide as oxidant. The catalytic study showed the alkyl silylation could enhance the catalytic activity of Ti-SO<sub>3</sub>H/CC-600(2.0). High catalytic activity and reusability of the o-Ti-SO<sub>3</sub>H/CC-600(2.0) were related to the modification of local environment of titanium active sites and the enhancement the hydrophobicity of catalyst particle by alkyl silylation. Copyright © 2017 BCREC GROUP. All rights reserved</p><p><em>Received: 24<sup>th</sup> May 2016; Revised: 11<sup>st</sup> October 2016; Accepted: 18<sup>th</sup> October 2016</em></p><p><strong>How to Cite:</strong> Nurhadi, M. (2017). Modification of Coal Char-loaded TiO<sub>2</sub> by Sulfonation and Alkylsilylation to Enhance Catalytic Activity in Styrene Oxidation with Hydrogen Peroxide as Oxidant. <em>Bulletin of Chemical Reaction Engineering &amp; Catalysis</em>, 12 (1): 55-61 (doi:10.9767/bcrec.12.1.501.55-61)</p><p><strong>Permalink/DOI</strong>: http://dx.doi.org/10.9767/bcrec.12.1.501.55-61</p><p> </p>


Author(s):  
Nurlykyz Yesmurzaeva ◽  
Roza Tursunova ◽  
Bagadat Selenova ◽  
Daulet Kaldybekov ◽  
Sarkyt Kudaibergenov

The present work is dedicated to investigation of vanadium xerogels deposited on titanium oxide for the oxidation process of o-xylene by hydrogen peroxide under the mild conditions. The structure of deposited vanadium catalyst and sizes of vanadium xerogels nanoparticles were investigated by physicochemical methods. The nano-sized particles (5-8 nm) of xerogel vanadium deposited on titanium oxide exhibit high catalytic activity in the decomposition of hydrogen peroxide and in the oxidation of o-xylene by hydrogen peroxide under mild conditions.


2015 ◽  
Vol 51 (100) ◽  
pp. 17728-17731 ◽  
Author(s):  
Yu-Xin Miao ◽  
Wen-Cui Li ◽  
Qiang Sun ◽  
Lei Shi ◽  
Lei He ◽  
...  

The exceptionally high catalytic activity for CO-PROX reaction is due to the Au–support interaction and the unique reducibility of the support.


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