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Proceedings of the National Academy of... Dec 2023
Topics: Dihydroorotate Dehydrogenase; Oxidoreductases Acting on CH-CH Group Donors; Oxidoreductases; Pyrimidines
PubMed: 38085787
DOI: 10.1073/pnas.2319097120 -
Chemical Society Reviews Mar 2021The nature of the terminal oxidant in oxidation reactions is an important reaction variable that can profoundly impact the mechanism, efficiency, and practicality of a... (Review)
Review
The nature of the terminal oxidant in oxidation reactions is an important reaction variable that can profoundly impact the mechanism, efficiency, and practicality of a synthetic protocol. One might reasonably categorize catalytic oxidation reactions into either "oxygenase" type reactions, in which the oxidant serves as an atom- or group-transfer reagent, or "oxidase" type reactions, where the oxidant is involved in catalyst turnover but does not become structurally incorporated into the product. As the field of photoredox catalysis has matured over the past decade, many successful oxygenase-type photoreactions have been reported. The development of photocatalytic oxidase reactions, on the other hand, has been somewhat slower. This tutorial review presents selected examples of some of the key classes of terminal oxidants that have been used in the design of photoredox oxidase transformations, along with the mechanistic features and benefits of each.
Topics: Catalysis; Hydrogen; Light; Oxidation-Reduction; Oxidoreductases; Oxygen; Peroxides; Transition Elements
PubMed: 33491681
DOI: 10.1039/d0cs00797h -
Chembiochem : a European Journal of... Jan 2021Sulfoxides are a class of organic compounds that find wide application in medicinal and organic chemistry. Several biocatalytic approaches have been developed to... (Review)
Review
Sulfoxides are a class of organic compounds that find wide application in medicinal and organic chemistry. Several biocatalytic approaches have been developed to synthesise enantioenriched sulfoxides, mainly by exploiting oxidative enzymes. Recently, the use of reductive enzymes such as Msr and Dms has emerged as a new, alternative method to obtain enantiopure sulfoxides from racemic mixtures. In parallel, novel oxidative approaches, employing nonclassical solvents such as ionic liquids (ILs) and deep eutectic solvents (DESs), have been developed as greener and more sustainable biocatalytic synthetic pathways. This minireview aims highlights the recent advances made in the biocatalytic synthesis of enantioenriched sulfoxides by employing such unconventional approaches.
Topics: Biocatalysis; Ferredoxin-NADP Reductase; Humans; Iron-Sulfur Proteins; Molecular Structure; Oxidoreductases; Sulfoxides
PubMed: 32735057
DOI: 10.1002/cbic.202000430 -
Molecules (Basel, Switzerland) Oct 2022The tumor-suppressor gene, WW domain-containing oxidoreductase (WWOX), has been found to be lost in various types of cancers. ROS result as a tightly regulated signaling...
The tumor-suppressor gene, WW domain-containing oxidoreductase (WWOX), has been found to be lost in various types of cancers. ROS result as a tightly regulated signaling process for the induction of cell senescence. The aim of this study was to investigate the role of WWOX in the regulation of ROS and cell senescence, which is intriguing in terms of the possible mechanism of WWOX contributing to bladder cancer. In this study, we used the AY-27 rat bladder tumor cell line and F344 orthotopic bladder tumor models to reveal the pro-senescence effects of WWOX and the corresponding underlying mechanism in bladder cancer. WWOX-overexpressing lentivirus (LV-WWOX) remarkably stimulated cellular senescence, including increased senescence-associated secretory phenotype (SASP) formation, enlarged cellular morphology, and induced SA-β-Gal-positive staining. A further mechanism study revealed that the pro-senescence effect of LV-WWOX was dependent on increased intercellular reactive oxygen species (ROS) generation, which subsequently triggered p21/p27. Moreover, LV-WWOX significantly inhibited the tumor size by 30.49% in the F344/AY-27 rat orthotopic model (p < 0.05) by activating cellular senescence. The expression of p21 was significantly enhanced in the orthotopic bladder tumors under WWOX treatment. The orthotopic bladder tumors in the groups of rats verified the effect in vivo. Our study suggests that WWOX, an ROS-dependent senescence-induced gene, could be further studied for its therapeutic implications in bladder cancer.
Topics: Rats; Animals; Urinary Bladder Neoplasms; Reactive Oxygen Species; Oxidoreductases; Rats, Inbred F344; Cellular Senescence; Cell Line, Tumor; WW Domain-Containing Oxidoreductase; Tumor Suppressor Proteins
PubMed: 36364214
DOI: 10.3390/molecules27217388 -
Sheng Wu Gong Cheng Xue Bao = Chinese... Dec 2021Methanogens are unique microorganisms for methane production and the main contributor of the biogenic methane in atmosphere. Methyl-coenzyme M reductase (Mcr) catalyzes... (Review)
Review
Methanogens are unique microorganisms for methane production and the main contributor of the biogenic methane in atmosphere. Methyl-coenzyme M reductase (Mcr) catalyzes the last step of methane production in methanogenesis and the first step of methane activation in anaerobic oxidation of methane. The genes encoding this enzyme are highly conserved and are widely used as a marker in the identification and phylogenetic study of archaea. There has been a longstanding interest in its unique cofactor F430 and the underpinning mechanisms of enzymatic cleavage of alkane C-H bond. The recent breakthroughs of high-resolution protein and catalytic-transition-state structures further advanced the structure-function study of Mcr. In particular, the recent discovery of methyl-coenzyme M reductase-like (Mcr-like) enzymes that activates the anaerobic degradation of non-methane alkanes has attracted much interest in the molecular mechanisms of C-H activation without oxygen. This review summarized the advances on function-structure-mechanism study of Mcr/Mcr-like enzymes. Additionally, future directions in anaerobic oxidation of alkanes and greenhouse-gas control using Mcr/Mcr-like enzymes were proposed.
Topics: Archaea; Methane; Oxidation-Reduction; Oxidoreductases; Phylogeny
PubMed: 34984864
DOI: 10.13345/j.cjb.200830 -
Journal of Microbiology and... Jun 2023Plant-derived insecticide-neonicotinoid insecticides (NIs) played a crucial role in the development of agriculture and food industry in recent years. Nevertheless,... (Review)
Review
Plant-derived insecticide-neonicotinoid insecticides (NIs) played a crucial role in the development of agriculture and food industry in recent years. Nevertheless, synthesis of these nitrogen-containing heterocyclic compounds with an effective and greener routing remains challenging especially to the notion raise of "green chemistry" and "atom economy". While bio-catalyzed methods mediated by nicotinate dehydrogenase (NDHase) then provide an alternative. The current review mainly focuses on the introduction of sources, components, structure, catalytic mechanism and applications of NDHase. Specifically, NDHase is known as nicotinic acid hydroxylase and the sources principally derived from phylum . In addition, NDHase requires the participation of the electron respiratory chain system on the cell membrane. And the most important components of the electron respiratory chain are hydrogen carrier, which is mainly composed of iron-sulfur proteins (Fe-S), flavin dehydrogenase (FAD), molybdenum binding protein and cytochromes. Heterologous expression studies were hampered by the plasmid and host with high efficiency and currently only L48 as well as was successfully utilized for the expression of NDHase. Furthermore, it is speculated that the conjugate and inductive effects of the substituent group at position 3 of the substrate pyridine ring exerts a critical role in the hydroxylation reactions at position 6 concerning about the substrate molecular recognition mechanism. Finally, applications of NDHase are addressed in terms of pesticide industry and wastewater treatment. On conclusion, this critical review would not only deepen our understanding of the theory about NDHase, but also provides the guideline for future investigation of NDHase.
Topics: Oxidoreductases Acting on CH-NH Group Donors; Plasmids
PubMed: 36959213
DOI: 10.4014/jmb.2302.02011 -
Microbial Cell Factories Oct 2017Cofactor engineering is involved in the modification of enzymes related to nicotinamide adenine dinucleotides (NADH and NAD) metabolism, which results in a significantly...
BACKGROUND
Cofactor engineering is involved in the modification of enzymes related to nicotinamide adenine dinucleotides (NADH and NAD) metabolism, which results in a significantly altered spectrum of metabolic products. Cofactor engineering plays an important role in metabolic engineering but is rarely reported in the sterols biotransformation process owing to its use of multi-catabolic enzymes, which promote multiple consecutive reactions. Androst-4-ene-3, 17-dione (AD) and androst-1, 4-diene-3, 17-dione (ADD) are important steroid medicine intermediates that are obtained via the nucleus oxidation and the side chain degradation of phytosterols by Mycobacterium. Given that the biotransformation from phytosterols to AD (D) is supposed to be a NAD-dependent process, this work utilized cofactor engineering in Mycobacterium neoaurum and investigated the effect on cofactor and phytosterols metabolism.
RESULTS
Through the addition of the coenzyme precursor of nicotinic acid in the phytosterols fermentation system, the intracellular NAD/NADH ratio and the AD (D) production of M. neoaurum TCCC 11978 (MNR M3) were higher than in the control. Moreover, the NADH: flavin oxidoreductase was identified and was supposed to exert a positive effect on cofactor regulation and phytosterols metabolism pathways via comparative proteomic profiling of MNR cultured with and without phytosterols. In addition, the NADH: flavin oxidoreductase and a water-forming NADH oxidase from Lactobacillus brevis, were successfully overexpressed and heterologously expressed in MNR M3 to improve the intracellular ratio of NAD/NADH. After 96 h of cultivation, the expression of these two enzymes in MNR M3 resulted in the decrease in intracellular NADH level (by 51 and 67%, respectively) and the increase in NAD/NADH ratio (by 113 and 192%, respectively). Phytosterols bioconversion revealed that the conversion ratio of engineered stains was ultimately improved by 58 and 147%, respectively. The highest AD (D) conversion ratio by MNR M3N2 was 94% in the conversion system with soybean oil as reaction media to promote the solubility of phytosterols.
CONCLUSIONS
The ratio of NAD/NADH is an important factor for the transformation of phytosterols. Expression of NADH: flavin oxidoreductase and water-forming NADH oxidase in MNR improved AD (D) production. Besides the manipulation of key enzyme activities, which included in phytosterols degradation pathways, maintenance the balance of redox also played an important role in promoting steroid biotransformation. The recombinant MNR strain may be useful in industrial production.
Topics: Androstadienes; FMN Reductase; Lactobacillus; Metabolic Engineering; Multienzyme Complexes; Mycobacterium; NAD; NADH, NADPH Oxidoreductases; Oxidation-Reduction; Phytosterols; Plasmids; Transcription, Genetic
PubMed: 29084539
DOI: 10.1186/s12934-017-0796-4 -
The Journal of General and Applied... Jan 2020Ferredoxin NADP oxidoreductase (Fpr) and oxygen-insensitive NAD(P)H nitroreductase (NfnB) are purified from Escherichia coli JM109 (E. coli JM109) as a predominant free...
Ferredoxin NADP oxidoreductase (Fpr) and oxygen-insensitive NAD(P)H nitroreductase (NfnB) are purified from Escherichia coli JM109 (E. coli JM109) as a predominant free flavin-independent ferric reductase. In the present study, we prepared natural iron storage proteins, E. coli ferritin A (FtnA) and bacterioferritin (Bfr), to show the effective ferrous iron release from these proteins by Fpr and NfnB in the presence of free flavins. Fpr and NfnB showed flavin reductase activity for flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN) and riboflavin, and their ferrous iron release activities were positively associated with the catalytic efficiencies (k/K) for individual flavins. The ferrous iron release activity of E. coli cell-free extracts was affected by flavin reductase activity of the extracts. The Butyl TOYOPEARL column chromatography of the extracts, on the basis of NAD(P)H-dependent flavin reductase activity, resulted in the separation of six active fractions containing Fpr, NfnB, NAD(P)H-quinone oxidoreductase (QOR), flavin reductase (Fre) or alkyl hydroperoxide reductase subunit F (AhpF) as major components. Like Fpr and NfnB, recombinant QOR, Fre, and AhpF showed flavin reductase activity and ferrous iron release activity in the presence of free flavins, indicating an association of flavin reductase activity with ferrous iron releasing activity. Taken together, both free flavin-dependent and free flavin-independent ferric reductases in E. coli require free flavins to mediate an electron transfer from NAD(P)H to ferric iron in the iron storage proteins for the effective ferrous iron release.
Topics: Catalysis; Escherichia coli; Escherichia coli Proteins; FMN Reductase; Ferritins; Flavins; Iron; Kinetics; NADH, NADPH Oxidoreductases; Oxidation-Reduction
PubMed: 31281172
DOI: 10.2323/jgam.2019.03.001 -
Enzyme and Microbial Technology Sep 2023Enzyme immobilization offers considerable advantage for biocatalysis in batch and continuous flow reactions. However, many currently available immobilization methods...
Enzyme immobilization offers considerable advantage for biocatalysis in batch and continuous flow reactions. However, many currently available immobilization methods require that the surface of the carrier is chemically modified to allow site specific interactions with their cognate enzymes, which requires specific processing steps and incurs associated costs. Two carriers (cellulose and silica) were investigated here, initially using fluorescent proteins as models to study binding, followed by assessment of industrially relevant enzyme performance (transaminases and an imine reductase/glucose oxidoreductase fusion). Two previously described binding tags, the 17 amino acid long silica-binding peptide from the Bacillus cereus CotB protein and the cellulose binding domain from the Clostridium thermocellum, were fused to a range of proteins without impairing their heterologous expression. When fused to a fluorescent protein both tags conferred high avidity specific binding with their respective carriers (low nanomolar K values). The CotB peptide (CotB1p) induced protein aggregation in the transaminase and imine reductase/glucose oxidoreductase fusions when incubated with the silica carrier. The Clostridium thermocellum cellulose binding domain (CBDclos) allowed immobilization of all the proteins tested, but immobilization led to loss of enzymatic activity in the transaminases (< 2-fold) and imine reductase/glucose oxidoreductase fusion (> 80%). A transaminase-CBDclos fusion was then successfully used to demonstrate the application of the binding tag in repetitive batch and a continuous-flow reactor.
Topics: Biocatalysis; Enzymes, Immobilized; Cellulose; Oxidoreductases; Peptides; Transaminases; Silicon Dioxide; Glucose Dehydrogenases
PubMed: 37300919
DOI: 10.1016/j.enzmictec.2023.110268 -
Experimental Biology and Medicine... Mar 2015WW domain-containing oxidoreductase (WWOX) is a well-documented tumor suppressor protein that controls growth, survival, and metastasis of malignant cells. To counteract... (Review)
Review
WW domain-containing oxidoreductase (WWOX) is a well-documented tumor suppressor protein that controls growth, survival, and metastasis of malignant cells. To counteract WWOX's suppressive effects, cancer cells have developed many strategies either to downregulate WWOX expression or to functionally inactivate WWOX. Relatively unknown is, in the context of those cancers associated with certain viruses or bacteria, how the oncogenic pathogens deal with WWOX. Here we review recent studies showing different strategies utilized by three cancer-associated pathogens. Helicobactor pylori reduces WWOX expression through promoter hypermethylation, an epigenetic mechanism also occurring in many other cancer cells. WWOX has a potential to block canonical NF-κB activation and tumorigenesis induced by Tax, an oncoprotein of human T-cell leukemia virus. Tax successfully overcomes the blockage by inhibiting WWOX expression through activation of the non-canonical NF-κB pathway. On the other hand, latent membrane protein 2A of Epstein-Barr virus physically interacts with WWOX and redirects its function to trigger a signaling pathway that upregulates matrix metalloproteinase 9 and cancer cell invasion. These reports may be just "the tip of the iceberg" regarding multiple interactions between WWOX and oncogenic microbes. Further studies in this direction should expand our understanding of infection-driven oncogenesis.
Topics: Carcinogenesis; Deltaretrovirus; Down-Regulation; Helicobacter pylori; Herpesvirus 4, Human; Humans; Oxidoreductases; Signal Transduction; Tumor Suppressor Proteins; WW Domain-Containing Oxidoreductase
PubMed: 25488911
DOI: 10.1177/1535370214561957