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Bile acids (BA) are among the most abundant metabolites produced by the gut microbiome. Primary BAs produced in the liver are converted by gut bacterial 7-α-dehydroxylation into secondary BAs, which can differentially regulate host health via signaling based on their varying affinity for BA receptors. Despite the importance of secondary BAs in host health, the regulation of 7-α-dehydroxylation and the role of diet in modulating this process is incompletely defined. Understanding this process could lead to dietary guidelines that beneficially shift BA metabolism. Dietary fiber regulates gut microbial composition and metabolite production. We tested the hypothesis that feeding mice a diet rich in a fermentable dietary fiber, resistant starch (RS), would alter gut bacterial BA metabolism. Male and female wild-type mice were fed a diet supplemented with RS or an isocaloric control diet (IC). Metabolic parameters were similar between groups. RS supplementation increased gut luminal deoxycholic acid (DCA) abundance. However, gut luminal cholic acid (CA) abundance, the substrate for 7-α-dehydroxylation in DCA production, was unaltered by RS. Further, RS supplementation did not change the mRNA expression of hepatic BA producing enzymes or ileal BA transporters. Metagenomic assessment of gut bacterial composition revealed no change in the relative abundance of bacteria known to perform 7-α-dehydroxylation. P. ginsenosidimutans and P. multiformis were positively correlated with gut luminal DCA abundance and increased in response to RS supplementation. These data demonstrate that RS supplementation enriches gut luminal DCA abundance without increasing the relative abundance of bacteria known to perform 7-α-dehydroxylation.

Aberrations in the Hedgehog (Hh) signaling pathway are significantly prevailed in various cancers, including B-cell lymphoma. A critical facet of Hh signal transduction involves the dynamic regulation of the suppressor of fused homolog (SUFU)-glioma-associated oncogene homolog (GLI) complex within the kinesin family member 7 (KIF7)-supported ciliary tip compartment. However, the specific post-translational modifications of SUFU-GLI complex within this context have remained largely unexplored. Our study reveals a novel regulatory mechanism involving prolyl 4-hydroxylase 2 (P4HA2), which forms a complex with KIF7 and is essential for signal transduction of Hh pathway. We demonstrate that, upon Hh pathway activation, P4HA2 relocates alongside KIF7 to the ciliary tip. Here, it hydroxylates SUFU to inhibit its function, thus amplifying the Hh signaling. Moreover, the absence of P4HA2 significantly impedes B lymphoma progression. This effect can be attributed to the suppression of Hh signaling in stromal fibroblasts, resulting in decreased growth factors essential for malignant proliferation of B lymphoma cells. Our findings highlight the role of P4HA2-mediated hydroxylation in modulating Hh signaling and propose a novel stromal-targeted therapeutic strategy for B-cell lymphoma.

Mutants lacking functional HYD2 homoeologs showed improved seedling growth, but comparable or increased susceptibility to salt stress in tillering plants, suggesting a developmentally restricted role of HYD2 in salt response. Salinity stress threatens global food security by reducing the yield of staple crops such as wheat (Triticum ssp.). Understanding how wheat responds to salinity stress is crucial for developing climate resilient varieties. In this study, we examined the interplay between carotenoid metabolism and the response to salt (NaCl) stress, a specific form of salinity stress, in tetraploid wheat plants with mutations in carotenoid β-hydroxylase 1 (HYD1) and HYD2. Our investigation encompassed both the vulnerable seedling stage and the more developed tillering stage of wheat plant growth. Mutant combinations lacking functional HYD2 homoeologs, including hyd-A2 hyd-B2, hyd-A1 hyd-A2 hyd-B2, hyd-B1 hyd-A2 hyd-B2, and hyd-A1 hyd-B1 hyd-A2 hyd-B2, had longer first true leaves and slightly enhanced root growth during germination under salt stress compared to the segregate wild-type (control) plants. Interestingly, these mutant seedlings also showed decreased levels of neoxanthin and violaxanthin (xanthophylls derived from β-carotene) and an increase in β-carotene in roots. However, tillering hyd mutant and segregate wild-type plants generally did not differ in their height, tiller count, and biomass production under acute or prolonged salt stress, except for decreases in these parameters observed in the hyd-A1 hyd-B1 hyd-A2 hyd-B2 mutant that indicate its heightened susceptibility to salt stress. Taken together, these findings suggest a significant, yet developmentally restricted role of HYD2 homoeologs in salt-stress response in tetraploid wheat. They also show that hyd-A2 hyd-B2 mutant plants, previously demonstrated for possessing enriched nutritional (β-carotene) content, maintain an unimpaired ability to withstand salt stress.

The natural heterogeneity of guaiacyl (G) and syringyl (S) compounds resulting from lignin processing hampers their direct use as plant‐based chemicals and materials. Herein, we explore six short polyphenol oxidases (PPOs) from lignocellulose‐degrading ascomycetes for their capacity to react with G‐type and S‐type phenolic compounds. All six PPOs catalyze the ortho‐hydroxylation of G‐type compounds (guaiacol, vanillic acid, and ferulic acid), forming the corresponding methoxy‐ortho‐diphenols. Remarkably, a subset of these PPOs is also active towards S‐compounds (syringol, syringic acid, and sinapic acid) resulting in identical methoxy‐ortho‐diphenols. Assays with 18O2 demonstrate that these PPOs in particular catalyze ortho‐hydroxylation and ortho‐demethoxylation of S‐compounds and generate methanol as a co‐product. Oxidative (ortho−) demethoxylation of S‐compounds is a novel reaction for PPOs, which we propose occurs by a distinct reaction mechanism as compared to aryl‐O‐demethylases. We further show that addition of a reducing agent can steer the PPO reaction to form methoxy‐ortho‐diphenols from both G‐ and S‐type substrates rather than reactive quinones that lead to unfavorable polymerization. Application of PPOs opens for new routes to reduce the heterogeneity and methoxylation degree of mixtures of G and S lignin‐derived compounds. [ABSTRACT FROM AUTHOR]

We present a Cu/PTFE electrode for the CO2 reduction reaction with a high coverage of *OH which facilitates both the activation of CO2 and the C–C coupling, leading to a faradaic efficiency for ethylene exceeding 50% at an exceptionally low potential of −246 mV vs. RHE, with the maximum FEC2H4 reaching 60.3%. [ABSTRACT FROM AUTHOR]

Rieske dioxygenase enzymes can perform the cis‐dihydroxylation of aliphatic olefins, representing a potential green alternative to established methods of performing this important transformation. However, the activity of the natural enzymes in this context is low relative to their more well‐known activity in the cis‐dihydroxylation of aromatics. To enable the engineering of dioxygenase enzymes for improved activity in the dihydroxylation of aliphatic olefins, we have developed an assay system to detect the relevant diol metabolites produced from whole‐cell fermentation cultures. Optimization studies were carried out to maximize the sensitivity of the assay system, and its utility in the in vitro screening of enzyme variant libraries was demonstrated. The assay system was utilized in screening studies that identified Rieske dioxygenase variants with significantly improved activity in the dihydroxylation of aliphatic olefins relative to the wild‐type enzyme. [ABSTRACT FROM AUTHOR]

Background: Microbial-derived secondary bile acids (SBAs) are reabsorbed and sensed via host receptors modulating cellular inflammation and fibrosis. Feline chronic kidney disease (CKD) occurs with progressive renal inflammation and fibrosis, mirroring the disease pathophysiology of human CKD patients. Methods: Prospective cross-sectional study compared healthy cats (n = 6) with CKD (IRIS Stage 2 n = 17, Stage 3 or 4 n = 11). Single timepoint fecal samples from all cats underwent targeted bile acid metabolomics. 16S rRNA gene amplicon sequencing using DADA2 with SILVA taxonomy characterized the fecal microbiota. Results: CKD cats had significantly reduced fecal concentrations (median 12.8 ng/mg, Mann–Whitney p = 0.0127) of the SBA ursodeoxycholic acid (UDCA) compared to healthy cats (median 39.4 ng/mg). Bile acid dysmetabolism characterized by <50% SBAs was present in 8/28 CKD and 0/6 healthy cats. Beta diversity significantly differed between cats with <50% SBAs and > 50% SBAs (PERMANOVA p < 0.0001). Twenty-six amplicon sequence variants (ASVs) with >97% nucleotide identity to Peptacetobacter hiranonis were identified. P. hiranonis combined relative abundance was significantly reduced (median 2.1%) in CKD cats with <50% SBAs compared to CKD cats with >50% SBAs (median 13.9%, adjusted p = 0.0002) and healthy cats with >50% SBAs (median 15.5%, adjusted p = 0.0112). P. hiranonis combined relative abundance was significantly positively correlated with the SBAs deoxycholic acid (Spearman r = 0.5218, adjusted p = 0.0407) and lithocholic acid (Spearman r = 0.5615, adjusted p = 0.0156). Three Oscillospirales ASVs and a Roseburia ASV were also identified as significantly correlated with fecal SBAs. Clinical and translational importance: The gut-kidney axis mediated through microbial-derived SBAs appears relevant to the spontaneous animal CKD model of domestic cats. This includes reduced fecal concentrations of the microbial-derived SBA UDCA, known to regulate inflammation and fibrosis and be reno-protective. Microbes correlated with fecal SBAs include bai operon containing P. hiranonis , as well as members of Oscillospirales , which also harbor a functional bai operon. Ultimately, CKD cats represent a translational opportunity to study the role of SBAs in the gut-kidney axis, including the potential to identify novel microbial-directed therapeutics to mitigate CKD pathogenesis in veterinary patients and humans alike. [ABSTRACT FROM AUTHOR]

Boron trifluoride diethyl etherate, commonly referred to as BF3 ⋅ OEt2, plays a crucial role as a potent reagent in various organic transformations, particularly in the synthesis of heterocyclic systems through the establishment of carbon‐carbon & carbon‐heteroatom bonds. Its Lewis acid properties, reactivity, and stability at room temperature make it essential for a wide range of chemical reactions. BF3 ⋅ OEt2 demonstrates remarkable efficacy in processes such as hydroxylation of double bonds, epoxide cleavage, acid esterification, cyanation, coupling, and diverse cyclization reactions, surpassing other Lewis acids in performance. Its significant impact on organic synthesis extends to the formation of natural products, highlighting its profound significance in the realm of chemistry. The unique properties and versatility of boron trifluoride diethyl etherate make it a fundamental tool for a diverse array of chemical transformations. The numerous applications of this reagent in organic synthesis have prompted the development of a comprehensive review, focusing on its various roles and contributions in this field. [ABSTRACT FROM AUTHOR]

Covalent triazine frameworks (CTFs) are promising heterogeneous photocatalyst candidates owing to their excellent stability, conjugacy, and tunability. In this study, a series of CTFs decorated with different substituents (H, MeO, and F) were synthesised and utilised as photocatalysts for C−H activation reactions. The corresponding optoelectronic properties could be precisely regulated by the electronic effects of different substituents in the nanopore channels of the CTFs; these CTFs were effective photocatalysts for C−H activation in organic synthesis due to their unique structures and optoelectronic properties. Methoxy‐substituted CTF (MeO‐CTF) exhibited extraordinary catalytic performance and reusability in C−H functionalization by constructing an electronic donor‐acceptor system, achieving the highest yield in the photocatalytic C3–H hydroxylation of 2‐phenylimidazole[1,2‐α]pyridine. This strategy provides a new scaffold for the rational design of CTFs as efficient photocatalysts for organic synthesis. [ABSTRACT FROM AUTHOR]

This study employs density functional theory to investigate the structural, electronic, and mechanical properties of Co, Fe, and Ni Porphyrin-Like Graphene (N4-G) structures. The study reveals a preference for in-plane configurations of metal atoms on N-doped graphene. Analysis of Bulk modulus, band structure, density of states, and magnetization highlights the distinctive electronic behaviors of Fe-N4-G and Ni-N4-G, showcasing semiconductor characteristics with narrow indirect band gaps, while Co-N4-G exhibits metallic behavior. Notably, Ni-N4-G lacks magnetic properties, distinguishing it from the magnetic behavior observed in the other structures. The investigation extends to the potential application of these structures as novel and promising catalysts for methane hydroxylation, a process critical for clean-burning fuel production. The results indicate moderate energy barriers for Co-N4-G and Ni-N4-G, with Fe-N4-G displaying the highest barrier, approximately five times larger. These valuable findings suggest that Co-N4-G and Ni-N4-G would be a promising candidate catalyst for methane hydroxylation, offering effective and stable catalytic capabilities. Overall, these findings present these metal-N4-G structures as appealing options for environmentally friendly and cost-effective oxidation processes. [ABSTRACT FROM AUTHOR]

In light of the challenges associated with catalyst separation and recovery, as well as the low production efficiency resulting from intermittent operation for titanium silicalite-1 (TS-1) catalyzed phenol hydroxylation to dihydroxybenzene in the slurry bed, researchers keep on exploring the use of a continuous fixed bed to replace the slurry bed process in recent years. This study focuses on preparing a TS-1 coated structured catalyst on SiC foam, which exhibits significant process intensification in performance. We investigated the kinetics of this structured catalyst and compared it with those of extruded TS-1 catalyst; the dynamic equations of the two catalysts were obtained. It was observed that both catalysts followed E-R adsorption mechanism model, with an effective internal diffusion factor ratio between structured and extruded TS-1 of approximately 7.71. It was confirmed that the foamed SiC-based structured TS-1 catalyst exhibited significant improvements in phenol hydroxylation in fixed-bed reactor due to its well-developed pore structure, good thermal conductivity, excellent internal mass transfer performance, and short reactant diffusion distance, leading to higher utilization efficiency of active components. This finding also provides a foundation for designing and developing phenol hydroxylation processes in fixed-bed using structured catalysts through computational fluid dynamics calculations. [ABSTRACT FROM AUTHOR]

The dearomatization of aromatic substrates via photocatalytic methodologies has gained escalating prominence to access molecular complexity. Although much focus has been put on non‐active arenes, naphthols and N‐based heteroaromatics, arylamines have so far remained in the background. Herein, we report a photocatalytic strategy for the aerobic, dearomative hydroxylation of naphthylamines under visible‐light irradiation. Our investigation highlights singlet oxygen generation as a viable mechanism for aromaticity disruption, mitigating selectivity issues deriving from the direct oxidation of targeted arylamines. Finally, we showcased the synthetic value of the obtained dearomatized products in a late‐stage diversification campaign. [ABSTRACT FROM AUTHOR]

Hierarchically structured materials are considered to be one of the important options to enhance the mass transportation efficiency in microporous zeolites. Herein, we reported a highly efficient steam-assisted crystallization strategy for the synthesis of a hierarchical TS-1 zeolite with a tunable macropore size. The amorphous SiO2–TiO2 precursor dissolved gradually and acted as both a nutrient supplier and macropore template in situ. The framework Ti content of the synthesized TS-1 zeolites could be tuned over a wide range (Ti wt% = 0.70–1.39) by varying the Ti content of the SiO2–TiO2 precursor. Moreover, the pore size of the macropores could be modulated according to the particle size of the precursor based on the investigation of the formation mechanism of the macropores in the hierarchical TS-1 zeolite. The hierarchical TS-1 zeolite exhibited better catalytic activity in the epoxidation reaction of 1-hexene and hydroxylation of phenol compared to the typical microporous zeolites. The improved performance of the hierarchical TS-1 zeolite was probably caused by the improved diffusion performance of the hierarchical structure. [ABSTRACT FROM AUTHOR]

Manganese (Mn) oxides are promising cathode materials for rechargeable aqueous Zn‐ion batteries. However, the Mn dissolution in weakly acidic electrolytes always hinders the development of better aqueous Zn–Mn batteries. Herein, a hydroxylated manganese oxide cathode material (H‐MnO2) is fabricated using an electrochemical method for stable aqueous Zn–Mn batteries without relying on the Mn2+ electrolyte additives. The partial hydroxylation of the oxides leads to charge redistribution of the material, changing the reaction thermodynamics and kinetics. Theoretical simulation suggests that the hydroxylation of manganese oxide promotes both Zn2+ adsorption thermodynamics and diffusion kinetics on the surface of H‐MnO2 but weakens the interaction between H+ and the electrode. Therefore, Zn2+ ions can be more reactive with the hydroxylated manganese oxide than H+ ions. Experimental results show that the Zn2+ insertion mechanism dominates the charge storage process of H‐MnO2, and the H+‐induced Mn dissolution reaction is effectively alleviated. Importantly, H‐MnO2 exhibits good cycling stability with 95% capacity retention over 5000 cycles at the current density of 3.8 A g−1 in the ZnSO4 electrolyte, outperforming the state‐of‐the‐art aqueous Zn–Mn batteries, even those with Mn2+ electrolyte additives. The findings provide new insights for designing stable manganese oxide cathodes in aqueous Zn–Mn batteries. [ABSTRACT FROM AUTHOR]

Simple Summary: Niclosamide, a drug originally used to treat parasitic infections, has shown potential as a possible cancer treatment, but poor absorptive and solubility properties are believed to limit its effectiveness. Researchers are exploring modified structures of the drug along with advanced delivery methods, particularly nanotechnology, to improve niclosamide's absorption profile and improve its specificity in regard to targeting cancerous cells. These efforts intend to produce more effective tumor-targeting compounds, which can be employed as pharmacological cancer treatment options when appropriate. If successful, these efforts will provide new tools for scientists and doctors, offering a novel approach regarding the treatment of a variety of different cancers and contribute to the elucidation of oncobiology. Inhibition of multiple cancer-related pathways has made niclosamide a promising candidate for the treatment of various cancers. However, its clinical application has been significantly limited by poor bioavailability. This review will discuss current findings on improving niclosamide bioavailability through modification of its chemical structure and utilization of novel nanotechnologies, like electrospraying and supercritical fluids, to improve drug delivery. For example, niclosamide derivatives, such as o-alkylamino-tethered niclosamide derivates, niclosamide ethanolamine salt, and niclosamide piperazine salt, have demonstrated increased water solubility without compromising anticancer activity in vitro. Additionally, this review briefly discusses recent findings on the first pass metabolism of niclosamide in vivo, the role of cytochrome P450-mediated hydroxylation, UDP-glucuronosyltransferase mediated glucuronidation, and how enzymatic inhibition could enhance niclosamide bioavailability. Ultimately, there is a need for researchers to synthesize, evaluate, and improve upon niclosamide derivatives while experimenting with the employment of nanotechnologies, such as targeted delivery and nanoparticle modification, as a way to improve drug administration. Researchers should strive to improve drug-target accuracy, its therapeutic index, and increase the drug's efficacy as an anti-neoplastic agent. [ABSTRACT FROM AUTHOR]

The effect of post-treatment of TS-1 zeolite by tetrapropyl ammonium hydroxide aqueous solution under hydrothermal condition was studied in this work. The characterizations of structure, morphology and composition demonstrated that an open and hierarchical porous structure was generated in TS-1 zeolite after the post-treatment. With increasing the alkalinity of TPAOH solution, the hierarchical porosity and hydrophobicity increased and the framework Ti content decreased in the post-treated TS-1 zeolite. Both the pristine and post-treated TS-1 zeolites were employed as the catalysts for the reaction of phenol hydroxylation. It was found that the post-treated TS-1 zeolite possessed a higher catalytic performance than the pristine TS-1 zeolite. The larger the alkalinity of the post-treatment solution was, the higher the catalytic performance of the post-treated TS-1 zeolite was; however, a too high alkalinity of the post-treatment solution also led to the decline in the catalytic performance. This could be a result of the combined influences of the hierarchical porosity, hydrophobicity and framework Ti content on the catalytic performance. The higher levels of hierarchical porosity and hydrophobicity promoted but the lower level of framework Ti content inhibited the catalytic performance of TS-1 zeolite. Accordingly, the controlling to the alkalinity of TPAOH solution for the post-treatment was very important in respect of the catalytic performance of TS-1 zeolite. [ABSTRACT FROM AUTHOR]

SUMMARY: Erianin, crepidatin, and chrysotobibenzyl are typical medicinal polymethoxylated bibenzyls (PMBs) that are commercially produced in Dendrobium species. PMBs' chemo‐diversity is mediated by the manifold combinations of O‐methylation and hydroxylation in a definite order, which remains unsolved. To unequivocally elucidate the methylation mechanism of PMBs, 15 possible intermediates in the biosynthetic pathway of PMBs were chemically synthesized. DcOMT1–5 were highly expressed in tissues where PMBs were biosynthesized, and their expression patterns were well‐correlated with the accumulation profiles of PMBs. Moreover, cell‐free orthogonal tests based on the synthesized intermediates further confirmed that DcOMT1‐5 exhibited distinct substrate preferences and displayed hydroxyl‐group regiospecificity during the sequential methylation process. The stepwise methylation of PMBs was discovered from SAM to dihydro‐piceatannol (P) in the following order: P → 3‐MeP → 4‐OH‐3‐MeP → 4‐OH‐3,5‐diMeP → 3,3'(4′),5‐triMeP → 3,4,4′,5‐tetraMeP (erianin) or 3,3′,4,5‐tetraMeP (crepidatin) → 3,3′,4,4′,5‐pentaMeP (chrysotobibenzyl). Furthermore, the regioselectivities of DcOMTs were investigated by ligand docking analyses which corresponded precisely with the catalytic activities. In summary, the findings shed light on the sequential catalytic mechanisms of PMB biosynthesis and provide a comprehensive PMB biosynthetic network in D. catenatum. The knowledge gained from this study may also contribute to the development of plant‐based medicinal applications and the production of high‐value PMBs. [ABSTRACT FROM AUTHOR]

Rieske dioxygenases have a long history of being utilized as green chemical tools in the organic synthesis of high‐value compounds, due to their capacity to perform the cis‐dihydroxylation of a wide variety of aromatic substrates. The practical utility of these enzymes has been hampered however by steric and electronic constraints on their substrate scopes, resulting in limited reactivity with certain substrate classes. Herein, we report the engineering of a widely used member of the Rieske dioxygenase class of enzymes, toluene dioxygenase (TDO), to produce improved variants with greatly increased activity for the cis‐dihydroxylation of benzoates. Through rational mutagenesis and screening, TDO variants with substantially improved activity over the wild‐type enzyme were identified. Homology modeling, docking studies, molecular dynamics simulations, and substrate tunnel analysis were applied in an effort to elucidate how the identified mutations resulted in improved activity for this polar substrate class. These analyses revealed modification of the substrate tunnel as the likely cause of the improved activity observed with the best‐performing enzyme variants. [ABSTRACT FROM AUTHOR]

A substantial increase in colorectal cancer (CRC)–associated fatalities can be attributed to tumor recurrence and multidrug resistance. Traditional treatment options, including radio- and chemotherapy, also exhibit adverse side effects. Ancient treatment strategies that include phytochemicals like resveratrol are now widely encouraged as an alternative therapeutic option. Resveratrol is the natural polyphenolic stilbene in vegetables and fruits like grapes and apples. It inhibits CRC progression via targeting dysregulated cancer-promoting pathways, including PI3K/Akt/Kras, targeting transcription factors like NF-κB and STAT3, and an immunosuppressive tumor microenvironment. In addition, combination therapies for cancer include resveratrol as an adjuvant to decrease multidrug resistance that develops in CRC cells. The current review discusses the biology of resveratrol and explores different mechanisms of action of resveratrol in inhibiting CRC progression. Further, the detrimental role of resveratrol on the immunosuppressive tumor microenvironment of CRC has been discussed. This review illustrates clinical trials on resveratrol in different cancers, including resveratrol analogs, and their efficiency in promoting CRC inhibition. [ABSTRACT FROM AUTHOR]

Propolis is a natural resinous compound produced by bees, mixed with their saliva and wax, and has a range of biological benefits, including antioxidant and anti-inflammatory effects. This article reviews the in vivo transformation of propolis flavonoids and their potential influence on drug efficacy. Despite propolis is widely used, there is little research on how the active ingredients of propolis change in the body and how they interact with drugs. Future research will focus on these interactions and the metabolic fate of propolis in vivo. [ABSTRACT FROM AUTHOR]

The efficient synthesis of an array of 1‐aryloxy‐1,1‐difluoro‐3‐aminopropan‐2‐ols in a one‐pot epoxidation/nucleophilic ring‐opening via the corresponding iodohydrines is described. This methodology permits the construction of 1,1‐difluorinated derivatives of commercialized beta‐blockers in addition to unprecedented members of this compound class. [ABSTRACT FROM AUTHOR]

The α‐hydroxy‐β‐dicarbonyl motif is essential in many biologically active compounds, sparking significant interest in their synthesis. This review comprehensively examines the advancements in the α‐hydroxylation of β‐dicarbonyl compounds, systematically categorizing the methods based on the types of oxidants employed and highlighting advances in asymmetric α‐hydroxylation. It evaluates the substrate scope, advantages, and disadvantages of each approach, summarizing the possible intermediates involved and the types of reaction mechanisms. [ABSTRACT FROM AUTHOR]

The enantioselective benzylic oxidation to synthesize chiral benzyl alcohols from alkylarenes poses a challenge. This study introduces a one-pot, two-step C–H bond hydroxylation process that integrates HRP-catalyzed oxidation and carbonyl reductase-catalyzed reduction for the enantiocomplementary synthesis of benzyl alcohols (up to 77% yield and 99% ee). This mild and operationally simple process provides an alternative approach to enantioselective benzylic hydroxylation. [ABSTRACT FROM AUTHOR]

Prolyl-hydroxylation is an oxygen-dependent posttranslational modification (PTM) that is known to regulate fibril formation of collagenous proteins and modulate cellular expression of hypoxia-inducible factor (HIF) α subunits. However, our understanding of this important but relatively rare PTM has remained incomplete due to the lack of biophysical methodologies that can directly measure multiple prolyl-hydroxylation events within intrinsically disordered proteins. Here, we describe a real-time 13C-direct detection NMR-based assay for studying the hydroxylation of two evolutionarily conserved prolines (P402 and P564) simultaneously in the intrinsically disordered oxygen-dependent degradation domain of hypoxic-inducible factor 1α by exploiting the "proton-less" nature of prolines. We show unambiguously that P564 is rapidly hydroxylated in a time-resolved manner while P402 hydroxylation lags significantly behind that of P564. The differential hydroxylation rate was negligibly influenced by the binding affinity to prolyl-hydroxylase enzyme, but rather by the surrounding amino acid composition, particularly the conserved tyrosine residue at the +1 position to P564. These findings support the unanticipated notion that the evolutionarily conserved P402 seemingly has a minimal impact in normal oxygen-sensing pathway. [ABSTRACT FROM AUTHOR]

Photocatalytic ozonation is considered to be a promising approach for the treatment of refractory organic pollutants, but the design of efficient catalyst remains a challenge. Surface modification provides a potential strategy to improve the activity of photocatalytic ozonation. In this work, density functional theory (DFT) calculations were first performed to check the interaction between O3 and TiO2−OH (surface hydroxylated TiO2) or TiO2−F (surface fluorinated TiO2), and the results suggest that TiO2−OH displays better O3 adsorption and activation than does TiO2−F, which is confirmed by experimental results. The surface hydroxyl groups greatly promote the O3 activation, which is beneficial for the generation of reactive oxygen species (ROS). Importantly, TiO2−OH displays better performance towards pollutants (such as berberine hydrochloride) removal than does TiO2−F and most reported ozonation photocatalysts. The total organic carbon (TOC) removal efficiency reaches 84.4 % within two hours. This work highlights the effect of surface hydroxylation on photocatalytic ozonation and provides ideas for the design of efficient photocatalytic ozonation catalysts. [ABSTRACT FROM AUTHOR]

Decarboxylative cross‐coupling reactions are powerful tools for carbon‐heteroatom bonds formation, but typically require pre‐activated carboxylic acids as substrates or heteroelectrophiles as functional groups. Herein, we present an electrochemical decarboxylative cross‐coupling of carboxylic acids with structurally diverse fluorine, alcohol, H2O, acid, and amine as nucleophiles. This strategy takes advantage of the ready availability of these building blocks from commercial libraries, as well as the mild and oxidant‐free conditions provided by electrochemical system. This reaction demonstrates good functional‐group tolerance and its utility in late‐stage functionalization. [ABSTRACT FROM AUTHOR]

Published data on salicylic acid synthesis methods based on the use of phenol, ortho-cresol, and benzoic acid are reviewed and analyzed. Current trends in the development of a technology based on the Kolbe–Schmitt process (production of aromatic and heteroaromatic hydroxy acids by treating alkali metal phenolates with CO2) are shown. Data on the effect of the catalyst system composition and benzoic acid hydroxylation process conditions on the achieved conversion and selectivity values and purity of the product are described. The review can be useful for choosing a suitable raw material base and a precursor conversion method for the development of domestic production of salicylic acid, which is a high-demand compound used in various industries. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: The development of catalytic asymmetric methods that enable access to value‐added functionalities or structures, exemplified by allylic alcohols, is a highly interesting yet challenging topic from both academic and industrial perspectives. However, before recent advances in chemical catalysis, there were scarce protocols toward constructing enantioenriched tertiary allylic alcohol scaffolds. In this context, peptide‐mimic phosphonium salts were found to be highly efficient in catalytic asymmetric α‐hydroxylation of α,β‐unsaturated and/or β,ϒ‐unsaturated compounds with satisfactory regio‐ and stereochemical outcomes (up to 97% yield and 95% ee). This methodology tolerates a broad array of substrates and thus provides an expeditious and unified platform for the assembly of enantioenriched tertiary allylic alcohols by avoiding the use of additional reductants and expensive metal catalysts. Furthermore, the power of this protocol is enlarged by simple conditions and the use of air as a source of hydroxyl functionality. [ABSTRACT FROM AUTHOR]

In this work, the self-made chrysotile fiber membrane (CFM) and raw chrysotile fiber (CF) were calcined in air from 500 to 800 °C. The XRD pattern of CFM showed that the diffraction peak of chrysotile weakened when the temperature was from room temperature to 550 °C, and CFM had a shorter amorphous interval at 600–700 °C. While, no amorphous phase appeared in CF during calcination, and forsterite begined to appear at 650 °C. SEM images showed that CFM could still maintain the integrity of the network structure at 600–800 °C, while CF gradually melted into coarse fiber bundles with the increase of calcination temperature, and sintering traces appeared. After that,the kinetics of the dehydroxylation of chrysotile in CFM and CF was studied. The dehydroxylation of CFM is a one-step reaction, the calculated activation energy is 243.33 kJ mol−1, which conforms to the two-dimensional ‘Valensi’ model with mechanism function G(α) = (1−α)ln(1−α) + α. The dehydroxylation of CF is divided into two stages, the activation energy are 222.87 kJ mol−1 and 316.04 kJ mol−1. The first stage of CF conforms to two-dimensional ‘Jander’ model (n = 2) with mechanism function G(α) = [1−(1−α)1/2]2, the second stage of CF conforms to the random nucleation and subsequent growth ‘Avrami-Erofeev’ model (n = 3/2) with mechanism function G(α) = [−ln(1−α)]2/3. [ABSTRACT FROM AUTHOR]

The present study employed sodium hexametaphosphate (SHMP) as a depressant for quartz to achieve selective flotation separation of lepidolite. Micro-flotation and artificial mixed-mineral tests confirmed that the introduction of SHMP successfully facilitated the separation of lepidolite and quartz under weak acid conditions. The MD simulations revealed that hydroxylation of non-bridging oxygen atoms on the quartz surface influenced the adsorption of dodecylamine (DDA), while it had no impact on the adsorption of sodium hexametaphosphate (SHMP). Additionally, SHMP was found to form hydrogen bonds with hydroxyl groups present on the quartz surface, thereby enhancing its adsorption capacity and indirectly promoting a higher degree of surface hydroxylation to impede DDA adsorption, thus preserving the hydrophilic nature of the quartz surface. Conversely, the dissolution of K+ in the [Si6-nAlnO6] (n=0, 1, 2) rings on the lepidolite surface in an aqueous environment leads to a negative charge on lepidolite. This negatively charged state presents obstacles for SHMP adsorption onto the lepidolite surface; however, it facilitates strong attraction and firm adsorption of positively charged DDA within the ring cavities of lepidolite, resembling an "anchor". The adsorption test revealed that, following treatment with SHMP, a substantial amount of DDA remained adsorbed onto the lepidolite, while only a negligible quantity was observed on the quartz surface. Consequently, the introduction of SHMP enables effective inhibition of quartz under conditions characterized by low hydroxylation levels on its surface (weak acid or neutral), thereby facilitating the production of high-quality lepidolite products. [ABSTRACT FROM AUTHOR]

Mycoparasite secondary metabolites control fungal infections or diseases in agriculture and human health. Among genes involved in synthesizing secondary metabolites, cytochrome P450 monooxygenases (CYPs/P450s) play a key role in synthesizing and attributing diversity to the secondary metabolites. Despite the importance of P450s, a comparative analysis of P450s in mycoparasites has yet to be reported. This study is aimed at addressing this research gap. Genome-wide analysis of P450s in 43 fungi representing six fungal phyla and three distinct lifestyles, such as mycoparasitic (24 species), saprophytic (5 species), and ectomycorrhizal (14 species), revealed the expansion of P450s in Pezizomycete mycoparasites for the synthesis of secondary metabolites. The number of P450s and their families and subfamilies, the number of secondary-metabolite biosynthetic gene clusters (SMBGCs), and the number of P450s that are part of these SMBGCs were found to be highest in Pezizomycete mycoparasites compared to their counterparts of saprophytes and ectomycorrhiza, indicating P450s also play a key role in mycoparasitism. An analysis of P450 location as part of SMBGCs and the available literature on Pezizomycete P450s revealed that P450s play a key role in the synthesis of anti-fungal secondary metabolites such as trichothecene sesquiterpene, harzianum A, heptelidic acid, and gliotoxin. The mycoparasite Trichoderma virens Tv29.8 P450 CYP68Q3 is found to be a bifunctional enzyme with epoxidation and oxidation capability, and CYP5117A3 performs a Baeyer–Villiger oxidation reaction with regioselectivity. This study serves as a reference for future annotation of P450s in mycoparasites. [ABSTRACT FROM AUTHOR]

FeII/α-ketoglutarate-dependent dioxygenases (Fe/αKG) make up a large enzyme family that functionalize C-H bonds on diverse organic substrates. Although Fe/αKG homologues catalyze an array of chemically useful reactions, hydroxylation typically predominates. Microalgal DabC uniquely forms a novel C-C bond to construct the bioactive pyrrolidine ring in domoic acid biosynthesis; however, we have identified that this kainoid synthase exclusively performs a stereospecific hydroxylation reaction on its cis substrate regioisomer. Mechanistic and kinetic analyses with native and alternative substrates identified a 20-fold rate increase in DabC radical cyclization over β-hydroxylation with no observable 1,5-hydrogen atom transfer. Moreover, this dual activity was conserved among macroalgal RadC1 and KabC homologues and provided insight into substrate recognition and reactivity trends. Investigation of this substrate-dependent chemistry improves our understanding of kainoid synthases and their biocatalytic application.

Hydroxylation of prolines to 4-trans-hydroxyproline (Hyp) is mediated by prolyl-4 hydroxylases (P4Hs). In plants, Hyps occur in Hydroxyproline-rich glycoproteins (HRGPs), and are frequently O-glycosylated. While both modifications are important, e.g. for cell wall stability, they are undesired in plant-made pharmaceuticals. Sequence motifs for prolyl-hydroxylation were proposed but did not include data from mosses, such as Physcomitrella. We identified six moss P4Hs by phylogenetic reconstruction. Our analysis of 73 Hyps in 24 secretory proteins from multiple mass spectrometry datasets revealed that prolines near other prolines, alanine, serine, threonine and valine were preferentially hydroxylated. About 95 % of Hyps were predictable with combined established methods. In our data, AOV was the most frequent pattern. A combination of 443 AlphaFold models and MS data with 3000 prolines found Hyps mainly on protein surfaces in disordered regions. Moss-produced human erythropoietin (EPO) exhibited O-glycosylation with arabinose chains on two Hyps. This modification was significantly reduced in a p4h1 knock-out (KO) Physcomitrella mutant. Quantitative proteomics with different p4h mutants revealed specific changes in protein amounts, and a modified prolyl-hydroxylation pattern, suggesting a differential function of the Physcomitrella P4Hs. Quantitative RT-PCR revealed a differential effect of single p4h KOs on the expression of the other five p4h genes, suggesting a partial compensation of the mutation. AlphaFold-Multimer models for Physcomitrella P4H1 and its target EPO peptide superposed with the crystal structure of Chlamydomonas P4H1 suggested significant amino acids in the active centre of the enzyme and revealed differences between P4H1 and the other Physcomitrella P4Hs.

Microbial biotransformation of argentatin A (1), isoargentatin A (2) and argentatin B (3), the cycloartane- and lanostane-type triterpenoid constituents of guayule (Parthenium argentatum) resin, with Cunninghamella elegans ATCC 9245-A0 afforded eight new metabolites 4–11. These were identified as products formed as a result of: (i) α- and β-hydroxylation at C-7 and C-11; (ii) sequential oxidation of these newly formed alcohols to their corresponding carbonyl analogues; and (iii) rearrangement of the 9(10)-cyclopropane ring. The observed regiospecific hydroxylation reactions are possibly catalyzed by cytochrome P450 enzymes known to be produced by C. elegans. It is interesting that among the biotransformation products 9–11 of argentatin B (3) with a carbonyl group at C-11, only 11 had resulted from the rearrangement of the 9(10)-cyclopropane ring under the conditions used for biotransformation. This constitutes the first report of biotransformation of argentatins by C. elegans. [ABSTRACT FROM AUTHOR]

Abstract Flavin-dependent monooxygenases (FMOs) are a valuable group of biocatalysts that can regioselectively introduce a hydroxy group for the targeted modification of biologically active compounds. Here, we present the fdeE, the FMO from Herbaspirillum seropedicae SmR1 that is a part of the naringenin degradation pathway and is active towards a wide range of flavonoids—flavanones, flavones, isoflavones, and flavonols. Bioinformatics and biochemical analysis revealed a high similarity between the analyzed enzyme and other F8H FMOs what might indicate convergent evolutionary mechanism of flavonoid degradation pathway emergence by microorganism. A simple approach with the manipulation of the reaction environment allowed the stable formation of hydroxylation products, which showed very high reactivity in both in vivo and in vitro assays. This approach resulted in an 8-hydroxyquercetin—gossypetin titer of 0.16 g/L and additionally it is a first report of production of this compound.

Abstract Background Bile acids (BAs) are steroid-derived molecules with important roles in digestion, the maintenance of host metabolism, and immunomodulation. Primary BAs are synthesized by the host, while secondary BAs are produced by the gut microbiome through transformation of the former. The regulation of microbial production of secondary BAs is not well understood, particularly the production of 7-dehydroxylated BAs, which are the most potent agonists for host BA receptors. The 7-dehydroxylation of cholic acid (CA) is well established and is linked to the expression of a bile acid-inducible (bai) operon responsible for this process. However, little to no 7-dehydroxylation has been reported for other host-derived BAs (e.g., chenodeoxycholic acid, CDCA or ursodeoxycholic acid, UDCA). Results Here, we demonstrate that the 7-dehydroxylation of CDCA and UDCA by the human isolate Clostridium scindens is induced when CA is present, suggesting that CA-dependent transcriptional regulation is required for substantial 7-dehydroxylation of these primary BAs. This is supported by the finding that UDCA alone does not promote expression of bai genes. CDCA upregulates expression of the bai genes but the expression is greater when CA is present. In contrast, the murine isolate Extibacter muris exhibits a distinct response; CA did not induce significant 7-dehydroxylation of primary BAs, whereas BA 7-dehydroxylation was promoted upon addition of germ-free mouse cecal content in vitro. However, E. muris was found to 7-dehydroxylate in vivo. Conclusions The distinct expression responses amongst strains indicate that bai genes are regulated differently. CA promoted bai operon gene expression and the 7-dehydroxylating activity in C. scindens strains. Conversely, the in vitro activity of E. muris was promoted only after the addition of cecal content and the isolate did not alter bai gene expression in response to CA. The accessory gene baiJ was only upregulated in the C. scindens ATCC 35704 strain, implying mechanistic differences amongst isolates. Interestingly, the human-derived C. scindens strains were also capable of 7-dehydroxylating murine bile acids (muricholic acids) to a limited extent. This study shows novel 7-dehydroxylation activity in vitro resulting from the presence of CA and suggests distinct bai gene expression across bacterial species.

Mycoparasite secondary metabolites control fungal infections or diseases in agriculture and human health. Among genes involved in synthesizing secondary metabolites, cytochrome P450 monooxygenases (CYPs/P450s) play a key role in synthesizing and attributing diversity to the secondary metabolites. Despite the importance of P450s, a comparative analysis of P450s in mycoparasites has yet to be reported. This study is aimed at addressing this research gap. Genome-wide analysis of P450s in 43 fungi representing six fungal phyla and three distinct lifestyles, such as mycoparasitic (24 species), saprophytic (5 species), and ectomycorrhizal (14 species), revealed the expansion of P450s in Pezizomycete mycoparasites for the synthesis of secondary metabolites. The number of P450s and their families and subfamilies, the number of secondary-metabolite biosynthetic gene clusters (SMBGCs), and the number of P450s that are part of these SMBGCs were found to be highest in Pezizomycete mycoparasites compared to their counterparts of saprophytes and ectomycorrhiza, indicating P450s also play a key role in mycoparasitism. An analysis of P450 location as part of SMBGCs and the available literature on Pezizomycete P450s revealed that P450s play a key role in the synthesis of anti-fungal secondary metabolites such as trichothecene sesquiterpene, harzianum A, heptelidic acid, and gliotoxin. The mycoparasite Trichoderma virens Tv29.8 P450 CYP68Q3 is found to be a bifunctional enzyme with epoxidation and oxidation capability, and CYP5117A3 performs a Baeyer–Villiger oxidation reaction with regioselectivity. This study serves as a reference for future annotation of P450s in mycoparasites.

Abstract Regioselective and enantioselective hydroxylation of propargylic C-H bonds are useful reactions but often lack appropriate catalysts. Here a green and efficient asymmetric hydroxylation of primary and secondary C–H bonds at propargylic positions has been established. A series of optically active propargylic alcohols were prepared with high regio- and enantioselectivity (up to 99% ee) under mild reaction conditions by using P450tol, while the C≡C bonds in the molecule remained unreacted. This protocol provides a green and practical method for constructing enantiomerically chiral propargylic alcohols. In addition, we also demonstrated that the biohydroxylation strategy was able to scaled up to 2.25 mmol scale with the production of chiral propargyl alcohol 2a at a yield of 196 mg with 96% ee, which’s an important synthetic intermediate of antifungal drug Ravuconazole. Graphical Abstract

Iodosilarene derivatives (PhIO, PhI(OAc)2) constitute an important class of oxygen atom transfer reagents in organic synthesis and are often used together with iron-based catalysts. Since the factors controlling the ability of iron centers to catalyze alkane hydroxylation are not yet fully understood, the aim of this report is to develop bioinspired non-heme iron catalysts in combination with PhI(OAc)2, which are suitable for performing C-H activation. Overall, this study provides insight into the iron-based ([FeII(PBI)3(CF3SO3)2] (1), where PBI = 2-(2-pyridyl)benzimidazole) catalytic and stoichiometric hydroxylation of triphenylmethane using PhI(OAc)2, highlighting the importance of reaction conditions including the effect of the co-ligands (para-substituted pyridines) and oxidants (para-substituted iodosylbenzene diacetates) on product yields and reaction kinetics. A number of mechanistic studies have been carried out on the mechanism of triphenylmethane hydroxylation, including C-H activation, supporting the reactive intermediate, and investigating the effects of equatorial co-ligands and coordinated oxidants. Strong evidence for the electrophilic nature of the reaction was observed based on competitive experiments, which included a Hammett correlation between the relative reaction rate (logkrel) and the σp (4R-Py and 4R'-PhI(OAc)2) parameters in both stoichiometric (ρ = +0.87 and +0.92) and catalytic (ρ = +0.97 and +0.77) reactions. The presence of [(PBI)2(4R-Py)FeIIIOIPh-4R']3+ intermediates, as well as the effect of co-ligands and coordinated oxidants, was supported by their spectral (UV–visible) and redox properties. It has been proven that the electrophilic nature of iron(III)-iodozilarene complexes is crucial in the oxidation reaction of triphenylmethane. The hydroxylation rates showed a linear correlation with the FeIII/FeII redox potentials (in the range of −350 mV and −524 mV), which suggests that the Lewis acidity and redox properties of the metal centers greatly influence the reactivity of the reactive intermediates. [ABSTRACT FROM AUTHOR]

Demonstrated here is an external photo‐sensitizer‐free (auto‐sensitized) singlet oxygen‐enabled solvent‐dependent tertiary hydroxylation and aryl‐alkyl spiro‐etherification of C3‐maleimidated quinoxalines. Such "reagent‐less" photo‐oxygenation at Csp3‐H and etherification involving Csp3‐H/Csp2‐H are unparalleled. Possibly, the highly π‐conjugated N‐H tautomer allows the substrate to get excited by irradiation, and subsequently, it attains the triplet state via ISC. This excited triplet‐state sensitized molecule then transfers its energy to a triplet‐state oxygen (3O2) generating reactive singlet oxygen (1O2) for hydroxylation and spirocyclization depending on the solvent used. In HFIP, the generated alkoxy radical accepts a proton via HAT giving hydroxylated product. In contrast, in an aprotic PhCl it underwent a radical addition at the ortho‐position of the C2 aryl to provide spiro‐ether. An unprecedented orthogonal spiro‐etherification was observed via the displacement of o‐substitutents for ortho (−OEt, −OMe, −F, −Cl, −Br) substituted substrates. The order of ipso substitution follows the trend −OMe>−OEt>−F>−H>−Cl>−Br. Both these oxygenation reactions can be carried out with nearly equal ease using direct sunlight without the requirement of any elaborate reaction setup. Demonstration of large‐scale synthesis and a few interesting transformations have also been realized. Furthermore, several insightful control experiments and quantum chemical computations were performed to unravel the mechanism. [ABSTRACT FROM AUTHOR]

Extracellular matrix (ECM) is a major component of the tumor environment, promoting the establishment of a pro-invasive behavior. Such environment is supported by both tumor- and stromal-derived metabolites, particularly lactate. In prostate cancer (PCa), cancer-associated fibroblasts (CAFs) are major contributors of secreted lactate, able to impact on metabolic and transcriptional regulation in cancer cells. Here, we describe a mechanism by which CAF-secreted lactate promotes in PCa cells the expression of genes coding for the collagen family. Lactate-exploiting PCa cells rely on increased α-ketoglutarate (α-KG) which activates the α-KG-dependent collagen prolyl-4-hydroxylase (P4HA1) to support collagen hydroxylation. De novo synthetized collagen plays a signaling role by activating discoidin domain receptor 1 (DDR1), supporting stem-like and invasive features of PCa cells. Inhibition of lactate-induced collagen hydroxylation and DDR1 activation reduces the metastatic colonization of PCa cells. Overall, these results provide a new understanding of the link between collagen remodeling/signaling and the nutrient environment exploited by PCa. Synopsis: Lactate, which is highly enriched in the prostate cancer environment, supports collagen remodeling and sensing in prostate cancer cells. Lactate-dependent metabolic rewiring sustains collagen hydroxylation via P4HA1 activation. De novo synthetized collagen activates discoidin domain receptor 1 (DDR1). P4HA1-DDR1-STAT3 axis is crucial for stemness and invasiveness of prostate cancer cells. Lactate, which is highly enriched in the prostate cancer environment, supports collagen remodeling and sensing in prostate cancer cells. [ABSTRACT FROM AUTHOR]

Herein, we report a general copper‐catalyzed method for the tunable oxygenative rearrangement of tetrahydrocarbazoles to cyclopentyl‐bearing spiroindolin‐2‐ones and spiroindolin‐3‐ones. The method demonstrates excellent chemoselectivity, regioselectivity, and product control simply by using the H2O and O2 as oxygen source, respectively. This open‐flask method is safe and simple to operate, and no other chemical oxidants are required. Besides, inspired from the unique pathway of 1, 2‐migration rearrangement, a highly controllable hydroxylation of indoles for the construction of C3a‐hydroxyl iminium indolines was also developed. Mechanistic experiments suggest that a single‐electron transfer‐induced oxidation process is responsible for the tunable selectivity control. [ABSTRACT FROM AUTHOR]

The hydroxylation of remote C(sp3)−H bonds in aliphatic amino acids yields crucial precursors for the synthesis of high‐value compounds. However, accurate regulation of the regioselectivity of remote C(sp3)−H bonds hydroxylation in aliphatic amino acids continues to be a common challenge in chemosynthesis and biosynthesis. In this study, the Fe(II)/α‐ketoglutarate‐dependent dioxygenase from Bacillus subtilis (BlAH) was mined and found to catalyze hydroxylation at the γ and δ sites of aliphatic amino acids. Crystal structure analysis, molecular dynamics simulations, and quantum chemical calculations revealed that regioselectivity was regulated by the spatial effect of BlAH. Based on these results, the spatial effect of BlAH was reconstructed to stabilize the transition state at the δ site of aliphatic amino acids, thereby successfully reversing the γ site regioselectivity to the δ site. For example, the regioselectivity of L‐Homoleucine (5 a) was reversed from the γ site (1 : 12) to the δ site (>99 : 1). The present study not only expands the toolbox of biocatalysts for the regioselective functionalization of remote C(sp3)−H bonds, but also provides a theoretical guidance for the precision‐driven modification of similarly remote C(sp3)−H bonds in complex molecules. [ABSTRACT FROM AUTHOR]

The peroxygenases are ideal biocatalysts for the selective oxyfunctionalisation of stable C-H bonds. However, the catalytic efficiency of this approach is limited due to enzyme lability toward oxidant H2O2. Although the reported in-situ H2O2 generation system enables the stable biocatalytic process without deactivating the enzyme, the greatest catalytic potential of peroxygenases still cannot be fulfilled effectively. To address the above issue, a H2O2 generation-detection-regulation platform that integrated an effective organocatalyst-driven H2O2 generation system, a precise electrochemical H2O2 real-time detection device, and a convenient H2O2 regulation strategy was first developed. The suitable range of H2O2 generation rate for maximizing the catalytic efficiency of perox-ygenases while minimizing inactivation of the enzyme was firstly obtained by simply adjusting the amount of organocatalyst. According to the determined suitable range, the C-H oxyfunctionalisation efficiency of peroxygenases for each substrate was significantly boosted, achieving ~3-fold of the reported highest turnover frequency. [ABSTRACT FROM AUTHOR]

Background: Bile acids (BAs) are steroid-derived molecules with important roles in digestion, the maintenance of host metabolism, and immunomodulation. Primary BAs are synthesized by the host, while secondary BAs are produced by the gut microbiome through transformation of the former. The regulation of microbial production of secondary BAs is not well understood, particularly the production of 7-dehydroxylated BAs, which are the most potent agonists for host BA receptors. The 7-dehydroxylation of cholic acid (CA) is well established and is linked to the expression of a bile acid-inducible (bai) operon responsible for this process. However, little to no 7-dehydroxylation has been reported for other host-derived BAs (e.g., chenodeoxycholic acid, CDCA or ursodeoxycholic acid, UDCA). Results: Here, we demonstrate that the 7-dehydroxylation of CDCA and UDCA by the human isolate Clostridium scindens is induced when CA is present, suggesting that CA-dependent transcriptional regulation is required for substantial 7-dehydroxylation of these primary BAs. This is supported by the finding that UDCA alone does not promote expression of bai genes. CDCA upregulates expression of the bai genes but the expression is greater when CA is present. In contrast, the murine isolate Extibacter muris exhibits a distinct response; CA did not induce significant 7-dehydroxylation of primary BAs, whereas BA 7-dehydroxylation was promoted upon addition of germ-free mouse cecal content in vitro. However, E. muris was found to 7-dehydroxylate in vivo. Conclusions: The distinct expression responses amongst strains indicate that bai genes are regulated differently. CA promoted bai operon gene expression and the 7-dehydroxylating activity in C. scindens strains. Conversely, the in vitro activity of E. muris was promoted only after the addition of cecal content and the isolate did not alter bai gene expression in response to CA. The accessory gene baiJ was only upregulated in the C. scindens ATCC 35704 strain, implying mechanistic differences amongst isolates. Interestingly, the human-derived C. scindens strains were also capable of 7-dehydroxylating murine bile acids (muricholic acids) to a limited extent. This study shows novel 7-dehydroxylation activity in vitro resulting from the presence of CA and suggests distinct bai gene expression across bacterial species. [ABSTRACT FROM AUTHOR]

Acid baking treatment is widely used to extract rare earth elements (REEs) from refractory rare earth bearing minerals such as monazite and xenotime. Since these REE minerals have been identified in coal-based sources, a parametric study was conducted to evaluate the impact and optimize the parametric values associated with the acid-baking process when treating a bituminous coal source. The parameters studied using a three-level statistical experimental program were acid baking time, acid solution concentration, baking temperature, and acid solution-to-solids ratio and each were found to significantly impact REE and contaminant element recovery. An increase in baking temperature up to around 250°C improved the light and heavy REE recovery values by more than 50 absolute percentage points relative to performances achieved when direct leaching. Acid baking was needed to dehydroxylate the clays and liberate the REE minerals, which allowed access for the acid to solubilize the REEs. Acid concentration of the solution used for acid baking was studied as a means of minimizing the amount of acid needed to achieve a target REE recovery. However, thermo-gravimetric and differential scanning calorimetry analysis (TGA-DSC) of sulfuric acid under oxidizing atmosphere revealed that the addition of water decreased the evaporation temperature, which explains the lower REE recovery values obtained when using lower acid concentrations. Using pure sulfuric acid at an acid-to-solid ratio of 0.8:1 resulted in recovery values of around 70% for both LREEs and HREEs. The decomposition reaction time was relatively quick with 65% of the TREEs recovered within the first 10 minutes. Water leaching experiments performed on the acid-baked products under a temperature of 25°C instead of 75°C revealed an increase in REE recovery by 10 absolute percentage points, which was likely due to the high solubility of REE-sulfates at room temperatures. [ABSTRACT FROM AUTHOR]

Background: Polysaccharide from Garcinia mangostana rind has many biological activities and deserves further research. Methods: The antioxidant properties of UAEE-GMRP, UAEE-GMRP-1 A, CM-30, and Ac-30 were evaluated through two different antioxidant activity experimental systems. Results: The four polysaccharides had a better scavenging effect on hydroxyl radicals, while their inhibitory effect on lipid peroxidation was relatively weak. However, overall, the four polysaccharides showed a certain degree of potential application in the two antioxidant experiments mentioned above, especially the chemically modified polysaccharides from Garcinia mangostana rind, which effectively improved their antioxidant activity. This also indicates that chemical modification is a better method to improve polysaccharide activity. In addition, in these two antioxidant exploration experiments, carboxymethylated polysaccharide showed stronger activity compared to the other three polysaccharides. Conclusion: The carboxymethylation modification may have great potential for application. [ABSTRACT FROM AUTHOR]

Major constituents of the plant cell walls are structural proteins that belong to the hydroxyproline-rich glycoprotein (HRGP) family. Leucine-rich repeat extensin (LRX) proteins contain a leucine-rich domain and a C-terminal domain with repetitive Ser–Pro3–5 motifs that are potentially to be O -glycosylated. It has been demonstrated that pollen-specific LRX8–LRX11 from Arabidopsis thaliana are necessary to maintain the integrity of the pollen tube cell wall during polarized growth. In HRGPs, including classical extensins (EXTs), and probably in LRXs, proline residues are converted to hydroxyproline by prolyl-4-hydroxylases (P4Hs), thus defining novel O -glycosylation sites. In this context, we aimed to determine whether hydroxylation and subsequent O -glycosylation of Arabidopsis pollen LRXs are necessary for their proper function and cell wall localization in pollen tubes. We hypothesized that pollen-expressed P4H4 and P4H6 catalyze the hydroxylation of the proline units present in Ser–Pro3–5 motifs of LRX8–LRX11. Here, we show that the p4h4-1 p4h6-1 double mutant exhibits a reduction in pollen germination rates and a slight reduction in pollen tube length. Pollen germination is also inhibited by P4H inhibitors, suggesting that prolyl hydroxylation is required for pollen tube development. Plants expressing pLRX11::LRX11-GFP in the p4h4-1 p4h6-1 background show partial re-localization of LRX11–green fluorescent protein (GFP) from the pollen tube tip apoplast to the cytoplasm. Finally, immunoprecipitation-tandem mass spectrometry analysis revealed a decrease in oxidized prolines (hydroxyprolines) in LRX11–GFP in the p4h4-1 p4h6-1 background compared with lrx11 plants expressing pLRX11::LRX11-GFP. Taken together, these results suggest that P4H4 and P4H6 are required for pollen germination and for proper hydroxylation of LRX11 necessary for its localization in the cell wall of pollen tubes. [ABSTRACT FROM AUTHOR]

The tert‐butyl group is a common aliphatic motif extensively employed to implement steric congestion and conformational rigidity in organic and organometallic molecules. Because of the combination of a high bond dissociation energy (~100 kcal mol−1) and limited accessibility, in the absence of directing groups, neither radical nor organometallic approaches are effective for the chemical modification of tert‐butyl C−H bonds. Herein we overcome these limits by employing a highly electrophilic manganese catalyst, [Mn(CF3bpeb)(OTf)2], that operates in the strong hydrogen bond donor solvent nonafluoro‐tert‐butyl alcohol (NFTBA) and catalytically activates hydrogen peroxide to generate a powerful manganese‐oxo species that effectively oxidizes tert‐butyl C−H bonds. Leveraging on the interplay of steric, electronic, medium and torsional effects, site‐selective and product chemoselective hydroxylation of the tert‐butyl group is accomplished with broad reaction scope, delivering primary alcohols as largely dominant products in preparative yields. Late‐stage hydroxylation at tert‐butyl sites is demonstrated on 6 densely functionalized molecules of pharmaceutical interest. This work uncovers a novel disconnection approach, harnessing tert‐butyl as a potential functional group in strategic synthetic planning for complex molecular architectures. [ABSTRACT FROM AUTHOR]

Regioselective and enantioselective hydroxylation of propargylic C-H bonds are useful reactions but often lack appropriate catalysts. Here a green and efficient asymmetric hydroxylation of primary and secondary C–H bonds at propargylic positions has been established. A series of optically active propargylic alcohols were prepared with high regio- and enantioselectivity (up to 99% ee) under mild reaction conditions by using P450tol, while the C≡C bonds in the molecule remained unreacted. This protocol provides a green and practical method for constructing enantiomerically chiral propargylic alcohols. In addition, we also demonstrated that the biohydroxylation strategy was able to scaled up to 2.25 mmol scale with the production of chiral propargyl alcohol 2a at a yield of 196 mg with 96% ee, which's an important synthetic intermediate of antifungal drug Ravuconazole. [ABSTRACT FROM AUTHOR]