Oxidation Step Research Articles

(5+1)−1] Cyclization of Nitroepoxides to Pyridinium 1,4‐Zwitterionic Thiolates for the Synthesis of Indolizine Derivatives

AbstractThe synthesis of indolizine derivatives was achieved through the reaction of pyridinium 1,4‐zwitterionic thiolates with a diverse array of 2‐methyl‐2‐nitro‐3‐aryloxiranes. Subsequent investigations unveiled a synthetic route to indolizines via a stepwise [(5+1)−1] pathway, with unstable pyridothiazines serving as transient intermediates. DFT calculations elucidated that this transformation entails sequential annulation, deacylation, desulfurization, and oxidation steps.

Tracking Water Dissociation on RuO2(110) Using Atomic Force Microscopy and First-Principles Simulations.

The interaction between interfacial water and transition metal oxides is a primary enabling step for the oxygen evolution reaction (OER). RuO2 is a prototypical OER electrocatalyst whose ability to activate interfacial water molecules is essential to its OER activity. We image the dissociation of surface water into OH* and O* on RuO2(110), where * denotes adsorbed species, using atomic force microscopy. Starting from the surface-bound water molecules, which form a one-dimensional network along the rows of Ru surface sites, increasing the oxidative potential strips hydrogen away and transforms the water molecules into OH* and O*. This oxidative step changes the pattern of the adsorbates from one- to two-dimensional. First-principles calculations with interfacial polarization, capacitive charging, and adsorbate interactions attribute this evolution to the cooperative dehydrogenation of adsorbed water and OH* on RuO2. We use these results to map the surface phase diagram of RuO2(110) and provide a quantitative interpretation of its cyclic voltammetry. Our result provides the visualization of the water dissociation on a conductive oxide surface, a critical step in the OER, and demonstrates that the water activation is a collective phenomenon at RuO2(110) electrodes.

Al-N3 Bridge Site Enabling Interlayer Charge Transfer Boosts the Direct Photosynthesis of Hydrogen Peroxide from Water and Air.

Manipulating the electronic environment of the reactive center to lower the energy barrier of the rate-determining water oxidation step for boosting the direct generation of H2O2 from water, air, and sunlight is fascinating yet remains a grand challenge. Driven by a first-principles screening across a series of metal single atoms in carbon nitride, we report a class of an Al-N3 bridge site enabling interlayer charge transfer in carbon nitride nanotubes (CNNT-Al) for the highly efficient photosynthesis of H2O2 directly from water, oxygen, and sunlight. We demonstrate that the interlayered Al-N3 bridge site in CNNT-Al is able to activate the neighboring surface N atom for promoting the rate-determining step of the two-electron water oxidation to H2O2. It is also able to act as a bridge for enhancing the vertical interlaminar charge transfer due to the hybridization between the 3s and 3p states of the interstitial Al atom and the conduction band of two adjacent carbon nitride layers. Collectively, these factors lead to a highest photocatalytic mass activity of 1410.2 μmol g-1 h-1 (with a photocatalyst concentration of 1 g L-1) for direct photosynthesis of H2O2 out of all CN-based photocatalysts and a 7-fold higher solar-to-chemical conversion efficiency (0.73%) compared to that of the natural photosynthesis of typical plants (∼0.1%). Most importantly, the CNNT-Al-based flow reactor can steadily produce H2O2 for 200 h and be directly used for the on-site degradation of organic dye in water. The CNNT-Al-based flow reactor can also kill a 10 times higher concentration of bacteria in deionized water than that in natural water with 100% efficiency, which makes our design economically appealing for practical water treatment.

Mechanistic Insights on Coverage-Dependent Selectivity Limitations in Vinyl Acetate Synthesis.

Developing improved catalysts for sustainable chemical processes often involves understanding atomistic origins of catalytic activity, selectivity, and stability. Using density functional theory and steady-state kinetic analyses, we probe the elementary steps that form decomposition products that limit selectivity in vinyl acetate (VA) synthesis on Pd surfaces covered with acetate species. Acetate formation and coupling with ethylene control the VA formation catalytic cycle and steady-state coverage, but acetate and ethylene can separately decompose to form CO2. Both decompositions involve initial C-H activations at acetate vacancies, followed by additional C-H activations and eventual C-O formations and C-C cleavages involving reactions with molecular oxygen. Acetate decomposition paths with non-oxidative kinetically-relevant steps exhibit similar free energy barriers to oxidative paths. In contrast, the non-oxidative ethylene path involving an ethylidyne intermediate exhibits a much lower barrier than paths with oxidative kinetically-relevant steps. Ethylene decomposition is very facile at low coverages but is more coverage-sensitive, leading to similar decomposition and VA formation barriers at coverages accessible at steady state, which is consistent with moderate VA selectivity in measurements and ethylene vs. acetate decomposition contributions assessed from regressed kinetic parameters. These insights provide a detailed framework for describing VA synthesis rates and selectivity on metallic catalyst surfaces.

A DFT study on the sulfur resistance mechanism of elemental mercury catalytic oxidation over Mn-Mo/CNT

The strong sulfur resistance of Mn-Mo/CNT during the process of elemental mercury catalytic oxidation at low temperature has been demonstrated in experiment. However, there remains a dearth of in-depth research on the sulfur resistance mechanism. This work aims to explore the sulfur resistance mechanism through density functional theory (DFT) calculations. The results reveal that SO2 can be effectively oxidized to SO3 through lattice oxygen on the surface of Mn-Mo/CNT. The speed control step is the step of SO3 dissociation, with an energy barrier of 2.50 eV. Additionally, O2 can adsorb onto active sites to supplement the consumed lattice oxygen. The adsorbed O2 can also oxidize SO2, and the highest energy barrier of this reaction is only 0.26 eV. SO3 can further react with the adsorbed Hg0 to form HgSO4, and the speed control step is the step of Hg0 oxidation. Specifically, when Hg0 is adsorbed onto Mo active sites, its energy barrier of speed control step reaches 4.06eV. Whereas, when Hg0 is adsorbed on Mn site, the energy barrier of speed control step reduces to 3.18eV. Generally, the coupling reaction process of Hg0 oxidation and SO2/SO3 conversion over Mn-Mo/CNT is the reason of the promotion in sulfur resistance of this catalyst.

Combined thermochemical-biotechnological approach for the valorization of polyolefins into polyhydroxyalkanoates: Development of an integrated bioconversion process by microbial consortia

Waste management of persistent polymers such as polyolefins (PO)1 still represents a major challenge, often leading to material loss from the value chain and contributing to plastic pollution. This study investigated an integrated process to valorize PO pyrolysis side stream. PO wax was recovered and used as a feedstock for a microbial bioconversion process. A modified emulsification protocol (using two-surfactants system) allowed the successful dispersion and bioconversion of PO wax without the need of the extra oxidation step. Enrichment of plastic landfill inocula allowed to develop efficient mixed microbial consortia (MMC) able to grow on PO wax. Adaptive laboratory evolution improved 4 times cell growth, leading to 2.6–17.3 times shorter lag phase. The bioconversion process using the adapted MMC was performed in a 2 L-bioreactor with PO wax-emulsified media (10 g L−1) at neutral pH and 20% pO2. 87% of substrate was consumed within 12 h and complete consumption was achieved within 48 h (4 times faster than previously reported). A maximum of 2.95 gCDW L−1of biomass was produced, while the intracellular triglycerides reached a maximum of 105.5 mg L−1 at 30 h. Moreover, the conversion of PO wax into polyhydroxyalkanoates (PHAs) was demonstrated and the production was maximized by statistical optimization. Maximum PHA titer of 384 0.1 mg L−1 was achieved, which represents a 1.5–17 times improvement from previous reports. This integrated thermochemical-biotechnological approach might represent an interesting strategy to valorize and upcycle currently unrecyclable PO-rich mixed plastic waste streams, thus improving the circularity of the plastic sector.

Exploring the Physicochemical, Antioxidant and Sensory Properties of the Flavoured Virgin Olive Oil With Chavir Extract During Storage

ABSTRACTThis study aimed to study the impact of Ferulago angulata (Schlecht) Boiss (known as an antioxidant known as Chavir) extract, obtained through ultrasound‐assisted extraction (UAE), on the physicochemical, antioxidant and sensory properties of virgin olive oil (VOO) during a 90‐day storage period at room temperature. For this purpose, different concentrations of Chavir extract (100, 200 and 300 ppm) were added to VOO. Key parameters, including total phenol content (TPC), extract composition by HPLC‐DAD and quality indicators like acidity value (AV), p‐anisidine value (p‐AV) and UV indices (parameters: K232, K270 and ΔK), were determined. AVs increased overall during the storage period, but adding Chavir extract at 300 ppm appeared to counteract the rise in free fatty acids, suggesting a potential role in reducing hydrolysis. p‐AVs decreased in unflavoured and flavoured samples, indicating reduced oxidation in Chavir‐flavoured VOO. K232 values exhibited a decline in the presence of flavouring agents and their concentrations. In contrast, the values of K270 showed an increase over the storage period, which indicated the formation of aldehyde and ketones in the second oxidation step. All samples maintained ΔK values below permissible limits (≥ 0.01), signifying good stability. The sensory evaluation emphasised positive attributes such as bitterness, fruitiness and pungency, indicating the high quality of VOO. The addition of Chavir extract further enhanced all of these positive characteristics, particularly at the 300 ppm concentration. However, a gradual decline was observed in all these attributes over time. Notably, the Chavir extract played a crucial role in delaying the formation of secondary oxidation products, which contribute to negative attributes like rancidity in VOO. Moreover, adding Chavir extract increases oxidative stability, infuses the positive qualities in VOO and provides valuable insights into its potential applications for enhancing the overall quality of VOO during storage. This enhancement not only helps maintain high quality and nutritional value but also makes the product more appealing to consumers.

Ethane-oxidising archaea couple CO2 generation to F420 reduction

The anaerobic oxidation of alkanes is a microbial process that mitigates the flux of hydrocarbon seeps into the oceans. In marine archaea, the process depends on sulphate-reducing bacterial partners to exhaust electrons, and it is generally assumed that the archaeal CO2-forming enzymes (CO dehydrogenase and formylmethanofuran dehydrogenase) are coupled to ferredoxin reduction. Here, we study the molecular basis of the CO2-generating steps of anaerobic ethane oxidation by characterising native enzymes of the thermophile Candidatus Ethanoperedens thermophilum obtained from microbial enrichment. We perform biochemical assays and solve crystal structures of the CO dehydrogenase and formylmethanofuran dehydrogenase complexes, showing that both enzymes deliver electrons to the F420 cofactor. Both multi-metalloenzyme harbour electronic bridges connecting CO and formylmethanofuran oxidation centres to a bound flavin-dependent F420 reductase. Accordingly, both systems exhibit robust coupled F420-reductase activities, which are not detected in the cell extract of related methanogens and anaerobic methane oxidisers. Based on the crystal structures, enzymatic activities, and metagenome mining, we propose a model in which the catabolic oxidising steps would wire electron delivery to F420 in this organism. Via this specific adaptation, the indirect electron transfer from reduced F420 to the sulphate-reducing partner would fuel energy conservation and represent the driving force of ethanotrophy.

On the interaction of uric acid with ammonium molybdate in acidic medium

This communication is a theoretical organic chemistry study on the interaction of uric acid with ammonium molybdate in acidic medium (Gigli test for uric acid). Colour tests give rapid, visible, results. However, it is interesting know what is happening in the test tube at molecular level. In the present paper we describe the reaction route of the above mentioned assay. Each step is fully commented and the electron flow is also given. The key stages are: addition of molybdic acid to the C-C double bond, acidolysis of the organometallic ester with reduction to molybdenum (IV) and epoxide formation (oxidation step). Ring opening of the oxirane and reaction with water. A glycol is formed followed by opening of the five-member ring giving a carbonyl and an ureido chain. Finally, elimination of urea gives rise to 2,4,5,6-tetraoxo-hexahydropyrimidine (alloxan) which is hydrated. The blue colour observed (molybdenum blue) is a mixture of several oxides.

Photochemical Synthesis of 7,12-Dioxa[8]helicene and Density Functional Theory Studies: Unravelling the One-Way Valve System Involving Steric Crowding and Aromatic Stability.

C2 symmetric chiral 7,12-dioxa[8]helicenes were synthesized through a series of photochemical E-Z isomerization, electrocyclic reaction, and oxidation steps in a stepwise sequential manner at both the ends of 2,9-di((E)-styryl)naphtho[2,1-b:7,8-b']difuran. The chemical transformations complemented with density functional theory (DFT) studies delineate some fundamental concepts, exhibiting counter current effects, namely, destabilization caused by increasing steric crowding and stabilization caused by aromatic units on the overall transformation. The calculated energy profile diagram unravels the formation of photoinduced intermediate species with increasing free energies for the E-Z isomerization and the electrocyclic reactions; the reverse processes for the said steps are prevented by a specific barrier-less oxidation step forming aromatic rings, presenting a one-way valve situation. The steric crowding-related increase in free energy and its counterbalancing by aromaticity have been illustrated for the helicene system using DFT studies. HOMA analysis shows that each individual ring in 7,12-dioxa[8]helicene exhibits a strong aromatic character, supporting the Fries model empirically. Interestingly, despite the nonplanar and sterically crowded geometry, 7,12-dioxa[8]helicene displayed a large HOMO-LUMO gap, typical of aromatic compounds.

Activity of novel virus families infecting soil nitrifiers is concomitant with host niche differentiation.

Chemolithoautotrophic nitrifiers are model groups for linking phylogeny, evolution, and ecophysiology. Ammonia-oxidising bacteria (AOB) typically dominate the first step of ammonia oxidation at high ammonium supply rates, ammonia-oxidising archaea (AOA) and complete ammonia-oxidising Nitrospira (comammox) are often active at lower supply rates or during AOB inactivity, and nitrite-oxidising bacteria (NOB) complete canonical nitrification. Soil virus communities are dynamic but contributions to functional processes are largely undetermined. In addition, characterising viruses infecting hosts with low relative abundance, such as nitrifiers, may be constrained by vast viral diversity, partial genome recovery, and difficulties in host linkage. Here, we describe a targeted incubation study that aimed to determine whether growth of different nitrifier groups in soil is associated with active virus populations and if process-focussed analyses facilitate characterisation of high-quality virus genomes. dsDNA viruses infecting different nitrifier groups were enriched in situ via differential host inhibition. Growth of each nitrifier group was consistent with predicted inhibition profiles and concomitant with the abundance of their viruses. These included 61 high-quality/complete virus genomes 35-173kb in length with minimal similarity to validated families. AOA viruses lacked ammonia monooxygenase sub-unit C (amoC) genes found in marine AOA viruses but some encoded AOA-specific multicopper oxidase type 1 (MCO1), previously implicated in copper acquisition, and suggesting a role in supporting energy metabolism of soil AOA. Findings demonstrate focussed incubation studies facilitate characterisation of active host-virus interactions associated with specific processes and viruses of soil AOA, AOB and NOB are dynamic and potentially influence nitrogen cycling processes.

Synthesis, Biophysical and Biological Evaluation of Splice-Switching Oligonucleotides with Multiple LNA-Phosphothiotriester Backbones.

Polyanionic antisense oligonucleotides hold great promise as RNA targeting drugs but issues with bioavailability hinder their development. Uncharged phosphorus-based backbones are promising alternatives but robust methods to produce them are limited. We report the synthesis and properties of oligonucleotides containing charge-neutral LNA alkyl phosphothiotriester backbones combined with 2'-O-methyl phosphorothioate nucleotides for therapeutic applications. The nature of the triester alkyl group dictates the success of solid-phase synthesis; tertiary alkyl groups are lost during the P(III) oxidation step, whereas primary alkyl groups are partially cleaved during deprotection. In contrast, oligonucleotides containing secondary phosphothiotriester linkages are stable, and large numbers of triesters can be incorporated. The modified oligonucleotides have excellent duplex stability with complementary RNA and exhibit strong nuclease resistance. To expand synthetic flexibility, oligonucleotides containing multiple internal alkynyl phosphothiotriesters can be conjugated to lipids, carbohydrates, or small molecules through CuAAC click chemistry. Oligonucleotides containing LNA-THP phosphothiotriesters exhibit high levels of pre-mRNA splice switching in eukaryotic cells.

Tandem Electrochemical Redox/Condensation Reaction Between 2‐Amino Nitrobenzenes and Aliphatic Alcohols: An Approach to Benzimidazoles

AbstractTandem reactions via electrocatalytic annulations have emerged as a strategy for the construction of heterocycles. Herein, a two‐component electrochemical annulation via sequential reduction, oxidation, and condensation steps to synthesize valuable benzimidazoles motifs is reported. This reaction, which utilizes electricity as both the oxidants and reductants, tolerates a broad range of functional groups. Detailed mechanistic studies including control experiments, cyclic voltammetry (CV) analysis, and key reaction intermediate characterization, reveals an intermolecular electrochemical redox/cyclization pathway.

Application of Iodine-Amine Oxidation Approach in the Synthesis of Various N-Alkyl Phosphoramidate Oligonucleotide Derivatives

Introduction: Nowadays, use of phosphate modifications in oligonucleotide backbone has become a common approach for imbuing its structure with the desired beneficial properties. The recent advances in successful application of different classes of phosphate modifications in the design of therapeutic oligonucleotides have led to a renewed interest in the development of approaches for introducing diverse classes of phosphate modifications. Method: This study aims to investigate the efficiency and optimize protocols for the application of the iodine-amine oxidation reaction to produce various N-alkyl phosphoramidate oligonucleotide derivatives during the conventional solid-phase phosphoramidite synthesis method. Result: Various solvents and drying reagents were tested, and it was evaluated that even minor traces of water in a reaction mixture had a significant impact on yield. Using set of commercially available amines, it was shown that steric accessibility is a more critical parameter than nucleophilicity of the amino group in oxidative amination reaction. It was demonstrated that through use of amino alcohols and diamines during iodine-amine oxidation step various branched oligonucleotide structures can be synthesized. Conclusion: The obtained data indicates that the oxidative amination approach can be a promising tool for preparing various oligonucleotide derivatives during solid-phase synthesis without the use of specialized phosphoramidite monomers.

Hydrogenation Studies of Iridium Pyridine Diimine Complexes with O- and S-Donor Ligands (Hydroxido, Methoxido and Thiolato)

For square-planar late transition metal pyridine, diimine (Rh, Ir) complexes with hydro-xido, methoxido, and thiolato ligands. We could previously establish sizable metal-O- and S π-bonding interactions. Herein, we report the hydrogenation studies of iridium hydroxido and methoxido complexes, which quantitatively lead to the trihydride compound and water/methanol. The iridium trihydride displays a highly fluctional structure with scrambling hydrogen atoms, which can be described as a dihydrogen hydride system based on NMR and DFT investigations. This contrasts the iridium sulfur compounds, which are not reacting with dihydrogen. According to DFT and LNO-CCSD(T) calculations, hydrogenation of the methoxido complex proceeds by a two-step mechanism, i.e., an oxidative addition step of H2 to an Ir(III) dihydride intermediate with consecutive reductive O-H elimination of methanol. Based on PNO-CCSD(T) calculations, the reactivity difference between the O- and S-donors can be traced to the stronger H-O bonds in the water/methanol products compared to the S-H bonds in the sulphur congeners, which serves as a driving force for hydrogenation.

DFT Investigation on Palladium-Catalyzed [2 + 2 + 1] Spiroannulation between Aryl Halides and Alkynes: Mechanism, Base Additive Role, and Solvent and Ligand Effects.

Transition metal-catalyzed spiroannulations are practical strategies for constructing spirocyclic skeletons of pharmaceutical and biological significance, yet the microscopic mechanism still lacks in-depth explorations. Here, the palladium-catalyzed [2 + 2 + 1] spiroannulation between aryl halides and alkynes was studied by employing the density functional theory (DFT) method. Based on comprehensive explorations on a couple of possible reaction pathways, it is found that the reaction probably experiences C-I oxidative addition, alkyne migration insertion, Cs2CO3-assisted aryl C-H activation, C-Br bond oxidative addition, C-C coupling, arene dearomatization and reductive elimination in sequence and leads to the formation of the spiro[4,5]decane pentacyclic product (P) ultimately. Among these, the C-Br bond oxidative addition step acts as the rate-determining step (RDS) of the whole reaction, featuring a practical free energy barrier of 32.4 kcal·mol-1 at 130 °C. Computationally predicted kinetics such as half-life transferred from the RDS step's barrier on the optimal reaction pathway (1.2 × 101 h) coincides well with corresponding experimental results (91% yield of the spiro[4,5]decane pentacyclic product P after reacting 10 h at 130 °C). In addition, theoretical predictions regarding the solvent/ligand effects and base additive role in the reaction, rationalized by distortion-interaction/natural population/noncovalent interaction analyses, are also in good agreement with experimental data and trend. This good agreement between experiment and theory makes sense for new designations and further experimental improvements of such Pd-catalyzed transformations.

Deciphering the Two-Step Hydride Mechanism of Monoamine Oxidase Flavoenzymes.

The complete two-step hydride transfer mechanism of amine oxidation involved in the metabolism of monoamine neurotransmitters was scrutinized by DFT calculations. In living organisms, this process is catalyzed by monoamine oxidase enzymes. Herein, we focus on some intriguing aspects of the reaction that may have been previously noticed but have not been clarified to date. The first step of the reaction includes the C-H bond cleavage on the methylene group vicinal to the amino group of the monoamine substrate and the subsequent transfer of hydrogen to the N5 atom of the flavin prosthetic group of the enzyme. We confirmed the nature of this step to be hydride transfer by evaluation of the pertinent HOMO-LUMO gap together with analysis of orbital contours alongside the intrinsic reaction coordinate profile. Next, we investigated the rather peculiar intermediate adduct that may form between the amine substrate and the flavin molecule, featuring an unusually long C-N bond of ∼1.62 Å. Although this bond is quite stable in the gas phase, the presence of just a few explicit water molecules facilitates its dissociation almost without energy input so that the amine-flavin intermediate can form an ionic pair instead. We attribute the existence of the unusual C-N bond to a fragile balance between opposing electronic structure effects, as evaluated by the natural bond orbital analysis. In line with this, the intermediate in the solution or in the enzyme active site can exist in two energetically almost equivalent forms, namely, as a covalently bound complex or as an ion pair, as suggested by previous studies. Finally, we characterized the transformation of the intermediate to the fully reduced flavin and imine products via proton transfer from the amino group to the flavin N1 atom, completing the reductive part of the catalytic cycle. Although we found that explicit solvation substantially boosts the kinetics of this step, the corresponding barrier is significantly lower than that in the hydride transfer step, confirming hydrogen abstraction as the rate-limiting step of amine oxidation and validating the two-step hydride transfer mechanism of monoamine oxidases.

Evaluation of the immune response of peripheral blood mononuclear cells cultured on Ti6Al4V-ELI polished or etched surfaces.

While titanium and its alloys exhibit excellent biocompatibility and corrosion resistance, their polished surfaces can hinder fast and effective osseointegration and other biological processes, such as angiogenesis, due to their inert and hydrophobic properties. Despite being commonly used for orthopedic implants, research focuses on developing surface treatments to improve osseointegration, promoting cell adhesion and proliferation, as well as increasing protein adsorption capacity. This study explores a chemical treatment intended for titanium-based implants that enhances tissue integration without compromising the mechanical properties of the Ti6Al4V substrate. However, recognizing that inflammation contributes to nearly half of early implant failures, we assessed the impact of this treatment on T-cell viability, cytokine production, and phenotype. Ti6Al4V with extra low interstitial (ELI) content discs were treated with hydrofluoric acid followed by a controlled oxidation step in hydrogen peroxide that creates a complex surface topography with micro- and nano-texture and modifies the chemistry of the surface oxide layer. The acid etched surface contains an abundance of hydroxyl groups, crucial for promoting bone growth and apatite precipitation, while also enabling further functionalization with biomolecules. While cell viability remained high in both groups, untreated discs triggered an increase in Th2 cells and a decrease of the Th17 subset. Furthermore, peripheral blood mononuclear cells exposed to untreated discs displayed a rise in various pro-inflammatory and anti-inflammatory cytokines compared to the control and treated groups. Conversely, the treated discs showed a similar profile to the control, both in terms of immune cell subset frequencies and cytokine secretion. The dysregulation of the cytokine profile upon contact with untreated Ti6Al4V-ELI discs, namely upregulation of IL-2 could be responsible for the decrease in Th17 frequency, and thus might contribute to implant-associated bacterial infection. Interestingly, the chemical treatment restores the immune response to levels comparable to the control condition, suggesting the treatment's potential to mitigate inflammation by enhancing biocompatibility.

Self-Resistance Gene-Guided Discovery of the Molecular Basis for Biosynthesis of the Fatty Acid Synthase Inhibitor Cerulenin.

Cerulenin (1) is the first reported natural fatty acid synthase inhibitor and has been intensively researched for its antifungal, anticancer and anti-obesity properties. However, the molecular basis for its biosynthesis has remained a mystery for six decades. Here, we have identified the polyketide biosynthetic gene cluster (cer) responsible for the biosynthesis of 1 from two Sarocladium species using a self-resistance gene mining approach, which we validated via heterologous reconstitution of cer cluster in an Aspergillus nidulans host. Expression of various combinations of cer genes uncovered key pathway intermediates, electrocyclisation products derived from PKS-encoded polyenoic acids, and a suite of 13 new analogues of 1. This enabled us to establish a biosynthetic pathway to 1 that starts with a C12 polyketide precursor containing both E and Z double bonds and involves a complex series of epoxidations, double bond shifts, E/Z isomerisation and epoxide reduction. Using in vitro assays, we further validated the roles of amidotransferase CerD in amidation, and oxidase CerF and reductase CerE in the final two-electron oxidation and enone reduction steps towards 1. These findings expand our understanding of complex tailoring modifications in highly reducing PKS pathways and pave the way for the engineered biosynthesis of cerulenin analogues.

High-fidelity propionaldehyde functionalized Poly(ethylene glycol): Synthesis and applications

An economical and efficient approach for synthesizing high-fidelity PEGn-Alds through a substitution and oxidation process has been developed, providing a new pathway for obtaining high-purity PEGn-Alds, particularly addressing the issue of peroxidation and breakage of PEG main chains in the oxidation step. The synthesis of a series of high-fidelity PEGn-Alds with different functional groups or topological structures further proves the versatility of this new method. Additionally, PEGn-Alds also exhibit good biocompatibility, and potential ability to modify peptides and self-assembly to micelles, this lays a foundation for synthesizing high-quality drugs and developing novel therapeutics.