Oxidative Decarboxylation Reaction Research Articles

Influence of molybdenum incorporation on the structural, chemical, and catalytic properties of iron cobaltite and cobalt ferrite catalysts

In this study, molybdenum doped iron cobaltite and cobalt ferrite catalysts were prepared by coprecipitation, and their structural, morphological, and optical, properties were evaluated by XRD, BET, SEM, FTIR, Raman, XPS and UV–VIS techniques. Their catalytic behavior evaluated in the malic acid oxidative decarboxylation reaction underlined the importance of the incorporation of Mo into the structure of iron cobaltite and cobalt ferrite catalysts. The catalysts with the highest molybdenum content forming cobaltite and iron molybdate phases showed better activity, with cobaltite-based catalysts being more active than ferrite-based ones.

Quinoline-Linked COF for the Photocatalytic Oxidative Decarboxylation and Homo-Coupling Reactions

Quinoline-Linked COF for the Photocatalytic Oxidative Decarboxylation and Homo-Coupling Reactions

Subunit composition of mitochondrial dehydrogenase complexes in diplonemid flagellates

In eukaryotes, pyruvate, a key metabolite produced by glycolysis, is converted by a tripartite mitochondrial pyruvate dehydrogenase (PDH) complex to acetyl-coenzyme A, which is fed into the tricarboxylic acid cycle. Two additional enzyme complexes with analogous composition catalyze similar oxidative decarboxylation reactions albeit using different substrates, the branched-chain ketoacid dehydrogenase (BCKDH) complex and the 2-oxoglutarate dehydrogenase (OGDH) complex. Comparative transcriptome analyses of diplonemids, one of the most abundant and diverse groups of oceanic protists, indicate that the conventional E1, E2, and E3 subunits of the PDH complex are lacking. E1 was apparently replaced in the euglenozoan ancestor of diplonemids by an AceE protein of archaeal type, a substitution that we also document in dinoflagellates. Here, we demonstrate that the mitochondrion of the model diplonemid Paradiplonema papillatum displays pyruvate and 2-oxoglutarate dehydrogenase activities. Protein mass spectrometry of mitochondria reveal that the AceE protein is as abundant as the E1 subunit of BCKDH. This corroborates the view that the AceE subunit is a functional component of the PDH complex. We hypothesize that by acquiring AceE, the diplonemid ancestor not only lost the eukaryotic-type E1, but also the E2 and E3 subunits of the PDH complex, which are present in other euglenozoans. We posit that the PDH activity in diplonemids seems to be carried out by a complex, in which the AceE protein partners with the E2 and E3 subunits from BCKDH and/or OGDH.

Combined Catalysis: A Powerful Strategy for Engineering Multifunctional Sustainable Lignin-Based Materials

The production and engineering of sustainable materials through green chemistry will have a major role in our mission of transitioning to a more sustainable society. Here, combined catalysis, which is the integration of two or more catalytic cycles or activation modes, provides innovative chemical reactions and material properties efficiently, whereas the single catalytic cycle or activation mode alone fails in promoting a successful reaction. Polyphenolic lignin with its distinctive structural functions acts as an important template to create materials with versatile properties, such as being tough, antimicrobial, self-healing, adhesive, and environmentally adaptable. Sustainable lignin-based materials are generated by merging the catalytic cycle of the quinone-catechol redox reaction with free radical polymerization or oxidative decarboxylation reaction, which explores a wide range of metallic nanoparticles and metal ions as the catalysts. In this review, we present the recent work on engineering lignin-based multifunctional materials devised through combined catalysis. Despite the fruitful employment of this concept to material design and the fact that engineering has provided multifaceted materials able to solve a broad spectrum of challenges, we envision further exploration and expansion of this important concept in material science beyond the catalytic processes mentioned above. This could be accomplished by taking inspiration from organic synthesis where this concept has been successfully developed and implemented.

Cu-Catalyzed Decarboxylative Annulation of N-Phenylglycines with Maleimides: Synthesis of 1H-Pyrrolo[3,4-c]quinoline-1,3(2H)-diones

A novel protocol for the construction of functionalized 1H-pyrrolo[3,4-c]quinoline-1,3(2H)-diones (PQLs, 3) from N-phenylglycines and maleimides was developed. The cascade reaction was enabled by heating a mixture of the two substrates in the presence of di-tert-butyl peroxide (DTBP) as an oxidant and anhydrous CuBr as a catalyst in chlorobenzene. Consequently, a diverse series of PQLs 3 were synthesized in moderate-to-good yields (43-73%). The synthesis of the PQLs was enabled via a one-pot cascade reaction that proceeded through subsequent oxidative decarboxylation, 1,2-addition, intramolecular cyclization, tautomerization, and aromatization reactions. This protocol can be used for the synthesis of functionalized PQLs via a one-pot oxidative decarboxylation annulation reaction rather than through a series of multistep reactions, making it suitable for both combinatorial and parallel syntheses of PQLs.

Metal -free PhI(OAc)2-oxidized decarboxylation of propiolic acids towards synthesis of α-acetoxy ketones and insights into general decarboxylation with DFT calculations.

A metal-free oxidative decarboxylation reaction of propiolic acids mediated by hypervalent iodine(III) reagents is described. This decarboxylative C-O bond-forming reaction used a combination of (diacetoxyiodo)benzene and aromatic, heteroaromatic or aliphatic propiolic acids to give the corresponding α-acetoxy ketones. Preliminary mechanistic studies based on both DFT calculations and high-resolution mass spectroscopy (HRMS) suggested that the reaction proceeded through decarboxylation to form a propargyl iodide intermediate. This reaction provides an attractive alternative to existing methods for the exclusive synthesis of α-acyloxy ketones.

Ultrastretchable, Adhesive, and Antibacterial Hydrogel with Robust Spinnability for Manufacturing Strong Hydrogel Micro/Nanofibers.

The ultrastretchable (over 12400%) hydrogel with long-lasting adhesion, strong antibacterial activity, and robust spinnability is developed based on the oxidative decarboxylation and quinone-catechol reversible redox reaction induced by Ag-lignin nanoparticles in a precursor solution containing citric acid (CA), acrylic acid (AA), and poly (acrylamide-co-acrylic acid) (P(AAm-co-AA)). With massive reversible interactions including hydrogen bonds and electrostatic forces, such hydrogel exhibits promising injectability and is facilely spun via manual drawing, draw-spinning, and electrospinning for manufacturing strong hydrogel micro/nanofibers. The resulting fibers exhibit excellent mechanical properties, including tensile stress of 422.0MPa, strain of 86.5%, Young's modulus of 8.7GPa, and toughness of 281.6MJ m-3 . The hydrogel microfibers obtained from a house-built spinner are scaled-up fabricated while retaining promising mechanical properties, as evidenced by lifting a load (317.2g) using the spun fibers of ≈33000 times lighter weight (9.5mg), indicating their great potentials in the applications such as net and safety cord which require robust mechanical properties. Moreover, assisted by a commercial electrospinning machine, nanosized hydrogel fibers are facilely spun on personal protective equipment such as a mask to offer an antiseptic coating with near 100% killing efficiency against airborne bacteria aerosols, demonstrating the capability of spun hydrogel fibers on disinfection-related applications.

Natural diversity of FAD-dependent 4-hydroxybenzoate hydroxylases

4-Hydroxybenzoate 3-hydroxylase (PHBH) is the most extensively studied group A flavoprotein monooxygenase (FPMO). PHBH is almost exclusively found in prokaryotes, where its induction, usually as a consequence of lignin degradation, results in the regioselective formation of protocatechuate, one of the central intermediates in the global carbon cycle. In this contribution we introduce several less known FAD-dependent 4-hydroxybenzoate hydroxylases. Phylogenetic analysis showed that the enzymes discussed here reside in distinct clades of the group A FPMO family, indicating their separate divergence from a common ancestor. Protein homology modelling revealed that the fungal 4-hydroxybenzoate 3-hydroxylase PhhA is structurally related to phenol hydroxylase (PHHY) and 3-hydroxybenzoate 4-hydroxylase (3HB4H). 4-Hydroxybenzoate 1-hydroxylase (4HB1H) from yeast catalyzes an oxidative decarboxylation reaction and is structurally similar to 3-hydroxybenzoate 6-hydroxylase (3HB6H), salicylate hydroxylase (SALH) and 6-hydroxynicotinate 3-monooxygenase (6HNMO). Genome mining suggests that the 4HB1H activity is widespread in the fungal kingdom and might be responsible for the oxidative decarboxylation of vanillate, an import intermediate in lignin degradation. 4-Hydroxybenzoyl-CoA 1-hydroxylase (PhgA) catalyzes an intramolecular migration reaction (NIH shift) during the three-step conversion of 4-hydroxybenzoate to gentisate in certain Bacillus species. PhgA is phylogenetically related to 4-hydroxyphenylacetate 1-hydroxylase (4HPA1H). In summary, this paper shines light on the natural diversity of group A FPMOs that are involved in the aerobic microbial catabolism of 4-hydroxybenzoate.

Reprogramming of aerobic glycolysis in non-transformed mouse liver with pyruvate dehydrogenase complex deficiency.

The Pyruvate Dehydrogenase Complex (PDC), a key enzyme in glucose metabolism, catalyzes an irreversible oxidative decarboxylation reaction of pyruvate to acetyl‐CoA, linking the cytosolic glycolytic pathway to mitochondrial tricarboxylic acid cycle and oxidative phosphorylation. Earlier we reported a down‐regulation of several key hepatic lipogenic enzymes and their upstream regulators in liver‐specific PDC‐deficient mouse (L‐PDCKO model by deleting the Pdha1 gene). In this study we investigated gene expression profiles of key glycolytic enzymes and other proteins that respond to various metabolic stresses in liver from L‐PDCKO mice. Transcripts of several, such as hexokinase 2, phosphoglycerate kinase 1, pyruvate kinase muscle‐type 2, and lactate dehydrogenase B as well as those for the nonglycolysis‐related proteins, CD‐36, C/EBP homologous protein, and peroxisome proliferator‐activated receptor γ, were up‐regulated in L‐PDCKO liver whereas hypoxia‐induced factor‐1α, pyruvate dehydrogenase kinase 1 and Sirtuin 1 transcripts were down‐regulated. The protein levels of pyruvate kinase muscle‐type 2 and lactate dehydrogenase B were increased whereas that of lactate dehydrogenase A was decreased in PDC‐deficient mouse liver. Analysis of endoplasmic reticulum and oxidative stress indicators suggests that the L‐PDCKO liver showed evidence of the former but not the latter. These findings indicate that (i) liver‐specific PDC deficiency is sufficient to induce “aerobic glycolysis characteristic” in mouse liver, and (ii) the mechanism(s) responsible for these changes appears distinct from that which induces the Warburg effect in some cancer cells.

Characterization of the Stereoselective P450 Enzyme BotCYP Enables the In Vitro Biosynthesis of the Bottromycin Core Scaffold.

Bottromycins are ribosomally synthesized and post-translationally modified peptide natural product antibiotics that are effective against high-priority human pathogens such as methicillin-resistant Staphylococcus aureus. The total synthesis of bottromycins involves at least 17 steps, with a poor overall yield. Here, we report the characterization of the cytochrome P450 enzyme BotCYP from a bottromycin biosynthetic gene cluster. We determined the structure of a close BotCYP homolog and used our data to conduct the first large-scale survey of P450 enzymes associated with RiPP biosynthetic gene clusters. We demonstrate that BotCYP converts a C-terminal thiazoline to a thiazole via an oxidative decarboxylation reaction and provides stereochemical resolution for the pathway. Our data enable the two-pot in vitro production of the bottromycin core scaffold and may allow the rapid generation of bottromycin analogues for compound development.

The impacts of parenteral vitamin B1, B6, B12 on hemoglobin levels in chronic kidney disease patients undergoing hemodialysis

Chronic kidney disease is a disorder of renal function and structure. The glomerular filtration rate was below the normal value and less than 60 ml/minute /1.73 m2 for more than 3 months. Patients with chronic kidney disease have erythropoietin in small amounts, and cause anemia. Vitamin B1 acts as oxidative decarboxylation reactions, B6 necessary to heme synthesis, and B12 converts homocysteine to methionine. This study aims to measure the impacts of parenteral vitamin B1, B6, B12 on hemoglobin level in chronic renal disease patients undergoing hemodialysis at Bethesda Hospital Yogyakarta and Panti Rapih Hospital Yogyakarta. The design of this study was one group pretest-posttest using secondary data from lab results from medical records. Data were collected from 117 patients using consecutive sampling methods at Bethesda Hospital Yogyakarta and Panti Rapih Hospital Yogyakarta in March 2019. The treatment given was parenteral vitamin B1, B6, B12 twice a week with a dose of 2 ml. Vitamin B was given intravenously after each hemodialysis. Hemoglobin levels were measured 3 times on 1st visit (before vitamin B administration), 2nd visit (after vitamin B administration), and 3rd visit (after vitamin B administration). There were significant differences of hemoglobin levels on 2nd visit compared to 1st visit (p = 0,000); 3rd visit compared to 1st visit (p = 0,000) and 3rd visit compared to 2nd visit (p = 0.010). Parenteral vitamin B1, B6, B12 gave significant impacts on hemoglobin level and was safe for chronic kidney disease patients undergoing hemodialysis.

Quinolactacin Biosynthesis Involves Non-Ribosomal-Peptide-Synthetase-Catalyzed Dieckmann Condensation to Form the Quinolone-γ-lactam Hybrid.

Quinolactacins are novel fungal alkaloids that feature a quinolone-γ-lactam hybrid, which is a potential pharmacophore for the treatment of cancer and Alzheimer's disease. Herein, we report the identification of the quinolactacin A2 biosynthetic gene cluster and elucidate the enzymatic basis for the formation of the quinolone-γ-lactam structure. We reveal an unusual β-keto acid (N-methyl-2-aminobenzoylacetate) precursor that is derived from the primary metabolite l-kynurenine via methylation, oxidative decarboxylation, and amide hydrolysis reactions. In vitro assays reveal two single-module non-ribosomal peptide synthetases (NRPs) that incorporate the β-keto acid and l-isoleucine, followed by Dieckmann condensation, to form the quinolone-γ-lactam. Notably, the bioconversion from l-kynurenine to the β-keto acid is a unique strategy employed by nature to decouple R*-domain-containing NRPS from the polyketide synthase (PKS) machinery, expanding the paradigm for the biosynthesis of quinolone-γ-lactam natural products via Dieckmann condensation.

POV remediation agents: α‐ketoglutarate salts and the treatment of citrus oils and citrus‐based model fragrances

AbstractIt is known that many terpenes can autoxidize under certain conditions to form terpene hydroperoxides, which have been reported to be contact allergens in dermatological clinics. The fragrance industry currently controls terpene hydroperoxide levels in many raw materials by iodometric titration (also known as the peroxide value or POV test) and rejects lots that exceed a specification limit. Previously, we have reported that pyruvic acid and its salts can be used to lower terpene hydroperoxide levels in citrus oils by an oxidative decarboxylation reaction, thus lowering the POV. However, both pyruvic acid and the by‐product acetic acid have strong aromas that are not compatible with citrus oils or other fragrances. For this reason, α‐ketoglutaric acid and its salts were tested. They were found to be highly effective and rapid at POV reduction in citrus oils and citrus‐based model fragrances. Both α‐ketoglutaric acid and the by‐product succinic acid are odourless; they are also both Krebs cycle intermediates, so there is practically no risk of systemic toxicity at relevant use levels.

Visible-light-promoted oxidative decarboxylation of arylacetic acids in air: Metal-free synthesis of aldehydes and ketones at room temperature

A metal-free photocatalytic oxidative decarboxylation reaction at room temperature was developed for the synthesis of aromatic aldehydes and ketones from the corresponding arylacetic acids. The reaction was realized under blue-light irradiation by adding 1 mol% of 4CzIPN as photocatalyst and air as oxidant. This reaction represents a novel decarboxylation of a sp3-hybridized carboxylic acids without traditional heating, additional oxidants, and metal reagents under mild conditions.

The flavin mononucleotide cofactor in α-hydroxyacid oxidases exerts its electrophilic/nucleophilic duality in control of the substrate-oxidation level.

The Y128F single mutant of p-hydroxymandelate oxidase (Hmo) is capable of oxidizing mandelate to benzoate via a four-electron oxidative decarboxylation reaction. When benzoylformate (the product of the first two-electron oxidation) and hydrogen peroxide (an oxidant) were used as substrates the reaction did not proceed, suggesting that free hydrogen peroxide is not the committed oxidant in the second two-electron oxidation. How the flavin mononucleotide (FMN)-dependent four-electron oxidation reaction takes place remains elusive. Structural and biochemical explorations have shed new light on this issue. 15 high-resolution crystal structures of Hmo and its mutants liganded with or without a substrate reveal that oxidized FMN (FMNox) possesses a previously unknown electrophilic/nucleophilic duality. In the Y128F mutant the active-site perturbation ensemble facilitates the polarization of FMNox to a nucleophilic ylide, which is in a position to act on an α-ketoacid, forming an N5-acyl-FMNred dead-end adduct. In four-electron oxidation, an intramolecular disproportionation reaction via an N5-alkanol-FMNred C'α carbanion intermediate may account for the ThDP/PLP/NADPH-independent oxidative decarboxylation reaction. A synthetic 5-deaza-FMNox cofactor in combination with an α-hydroxyamide or α-ketoamide biochemically and structurally supports the proposed mechanism.

Biochemical and structural explorations of α-hydroxyacid oxidases reveal a four-electron oxidative decarboxylation reaction.

p-Hydroxymandelate oxidase (Hmo) is a flavin mononucleotide (FMN)-dependent enzyme that oxidizes mandelate to benzoylformate. How the FMN-dependent oxidation is executed by Hmo remains unclear at the molecular level. A continuum of snapshots from crystal structures of Hmo and its mutants in complex with physiological/nonphysiological substrates, products and inhibitors provides a rationale for its substrate enantioselectivity/promiscuity, its active-site geometry/reactivity and its direct hydride-transfer mechanism. A single mutant, Y128F, that extends the two-electron oxidation reaction to a four-electron oxidative decarboxylation reaction was unexpectedly observed. Biochemical and structural approaches, including biochemistry, kinetics, stable isotope labeling and X-ray crystallography, were exploited to reach these conclusions and provide additional insights.

Investigating putative key catalytic residues and uncoupled hydroperoxyflavin formation in the mechanism of 6‐hydroxynicotinate‐3‐monooxygenase, a decarboxylative‐hydroxylase in bacterial nicotinate catabolism

Agrochemicals, pharmaceuticals and personal care products (APPCPs) are contaminants of emerging concern that are ineffectively remediated by current methodologies. Many APPCPs contain N‐heterocyclic aromatic constituents (NHACs) that are persistent contaminants in aquatic environments and cause adverse effects in non‐target organisms. Understanding bacterial degradation of NHACs may assist future bioremediation techniques. Aerobic bacterial catabolism of nicotinic acid (NA) serves as a model for understanding the biodegradation of NHACs, and a key enzyme of this pathway is 6‐hydroxynicotinate 3‐monooxygenase (NicC). We recently published the first crystal structure and two postulated mechanisms for NicC. Both mechanisms involve acid‐base catalysis, in which active site residue His211 may serve as a key H‐bond donor. Additionally, the Cys202 active site residue may donate a thiol group, playing a role in one postulated mechanism. Kinetic characterization of the H211A and C202A variants shows that the apparent substrate affinity and catalytic turnover are largely unaffected by mutagenesis of these bases (H211A: KM of 6HNA increases 2.1–fold, KM of NADH increases 2.3–fold, kcat increases 30% compared to WT; C202A: KM of 6HNA increases 2.4–fold, kcat drops 15‐fold). These data suggest that the His211 and Cys202 residues are not critical for catalysis. 6‐Hydroxynicotinaldehyde (6‐HNAH), a competitive inhibitor of NicC with respect to 6‐HNA, exhibits tight binding (KD of 6HNAH = 36 ± 2 μM) compared to 6HNA (KD of 6HNA = 190 ± 25 μM), but shows weak inhibition (Ki of 6HNAH = 8.5 ± 2.4 mM). These results are consistent with the possibility that the formation of hydroperoxyflavin (FADHOOH) is uncoupled from the oxidative decarboxylation reaction, and subsequently produces hydrogen peroxide. Hydrogen peroxide production was detected for reactions of WT+6HNAH and H211A+6HNAH, but not detected for WT+6HNA and H211A+6HNA, suggesting that 6HNAH causes uncoupling and His211 is not a key catalytic residue in the mechanism of NicC.Support or Funding InformationCollege of Wooster Sophomore Research ProgramThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Bacterial Genes of Non-Heme Iron Oxygenases, Which Have a Rieske-Type Cluster, Catalyzing Initial Stages of Degradation of Chlorophenoxyacetic Acids

Hydroxylation of the benzoic ring by non-heme iron oxygenases having a Rieske-type cluster is the key step in the aerobic degradation of chloroaromatic compounds by bacteria. Rieske oxygenases (RO) catalyze the oxidative decarboxylation reaction unique to the enzymes of this family with the formation of corresponding phenolic compounds. This review discusses the general structure, function, and classification of ROs that catalyze the oxidation of chlorophenoxyacetic acids; genes encoding the ROs with their phylogenetic classes are also reviewed.

Ca2+ Binding and Conformational Switch of the Photoprotein Mnemiopsin.

Bioluminescence in Ca2+-binding photoproteins is an intramolecular reaction triggered by the addition of Ca2+. A comparative study has been done on Ca2+-depleted and Ca2+-loaded apo-mnemiopsin to understand the structural transition of the photoprotein by Ca2+ binding. Ca2+ is removed by TCA (trichloroacetic acid) precipitation to obtain Ca2+-depleted apomnemiopsin. UV-visible, CD and fluorescence spectroscopic studies demonstrate that the addition of Ca2+ is brought about by the overall structure of apo-mnemiopsin becomes more open in a concentration- dependent manner without significantly influencing the secondary structure and indicate that the Ca2+-depleted form of apo-mnemiopsin, in contrast to most other EF-hand calcium binding proteins, adopt a closed conformation when compared to the Ca2+-loaded form. On the other hand, dynamic quenching and limited proteolysis analysis revealed that Ca2+-loaded apo-mnemiopsin became much more flexible than Ca2+ free apo-mnemiopsin. It seems that increased flexibility of the protein, which occurs due to calcium binding, is a critical factor in oxidative decarboxylation reaction on coelenterazine and consequently light emission.

A Structure‐Based Mechanism for Oxidative Decarboxylation Reactions Mediated by Amino Acids and Heme Propionates

Coproheme decarboxylase catalyzes two sequential oxidative decarboxylations with H2O2 as the oxidant, coproheme III as substrate and cofactor, and heme b as the product. Each reaction breaks a C‐C bond and results in net loss of hydride, via steps that are not clear. Solution and solid‐state structural characterization of the protein in complex with a substrate analog has revealed a highly unconventional H2O2‐activating distal environment with the reactive propionic acids (2 and 4) on the opposite side of the porphyrin plane. This suggests that, in contrast to direct C‐H bond cleavage catalyzed by a high‐valent iron intermediate, the coproheme oxidations must occur through mediating amino acid residues. A tyrosine that hydrogen bonds to propionate 2 in a position analogous to the substrate in ascorbate peroxidase is essential for both decarboxylations, while a lysine that salt bridges to propionate 4 is required solely for the second. A mechanism is proposed in which propionate 2 relays an oxidizing equivalent from a coproheme compound I intermediate to the reactive deprotonated tyrosine, forming Tyr■. This residue then abstracts a net hydrogen atom (H■) from propionate 2, followed by migration of the unpaired propionyl electron to the coproheme iron to yield the ferric harderoheme and CO2 products. A similar pathway is proposed for decarboxylation of propionate 4, but with a lysine residue as an essential proton shuttle. The proposed reaction suggests an unprecedented relay of heme‐mediated e−/H+ transfers and a novel route for the conversion of carboxylic acids to alkenes.