JACS Au最新文献

Synthetic plastics have become integral to our daily lives, yet their escalating production, limited biodegradability, and inadequate waste management contribute to environmental contamination. Biological plastic degradation is one promising strategy to address this pollution. The inherent chemical and physical properties of synthetic plastics, however, pose challenges for microbial enzymes, hindering the effective degradation and the development of a sustainable biological recycling process. This Perspective explores alternative, nature-inspired strategies designed to overcome some key limitations in currently available plastic-degrading enzymes. Nature’s refined degradation pathways for natural polymers, such as cellulose, present a compelling framework for the development of efficient technologies for enzymatic plastic degradation. By drawing insights from nature, we propose a general strategy of employing substrate binding domains to improve targeting and multienzyme scaffolds to overcome enzymatic efficiency limitations. As one potential application, we outline a multienzyme pathway to upcycle polyethylene into alkenes. Employing nature-inspired strategies can present a path toward sustainable solution to the environmental impact of synthetic plastics.

Aldehyde dehydrogenase (ALDH) is an enzyme responsible for converting aldehyde functional groups into carboxylate metabolites. Elevated ALDH activity is a characteristic feature of cancer stem-like cells (CSCs). As a novel approach to target the CSC trait of overexpressing ALDH, we aimed to utilize ALDH activity for the selective accumulation of a photosensitizer in ALDH^High CSCs. A novel ALDH substrate photosensitizer, SCHO, with thionylated coumarin and N-ethyl-4-(aminomethyl)benzaldehyde was developed to achieve this goal. Our study demonstrated the efficient metabolism of the aldehyde unit of SCHO into carboxylate, leading to its accumulation in ALDH^High MDA-MB-231 cells. Importantly, we established the selectivity of SCHO as an ALDH^High cell photosensitizer as it is not a substrate for ABC transporters. SCHO-based photodynamic therapy triggers apoptosis and pyroptosis in MDA-MB-231 cells and further reduces the characteristics of CSCs. Our study presents a novel strategy to target CSCs by exploiting their cellular metabolism to enhance photosensitizer accumulation, highlighting the potential of photodynamic therapy as a powerful tool for eliminating ALDH^High CSCs.

Selective activation of light alkanes is an essential reaction in the petrochemical industry for producing commodity chemicals, such as light olefins and aromatics. Because of the much higher intrinsic activities of noble metals in comparison to non-noble metals, it is desirable to employ solid catalysts with low noble metal loadings to reduce the cost of catalysts. Herein, we report the introduction of a tiny amount of Pt (at levels of hundreds of ppm) as a promoter of the Ga₂O₃ clusters encapsulated in ZSM-5 zeolite, which leads to ∼20-fold improvement in the activity for ethane dehydrogenation reaction. A combination of experimental and theoretical studies shows that the isolated Pt atoms stabilized by small Ga₂O₃ clusters are the active sites for activating the inert C–H bonds in ethane. The synergy of atomically dispersed Pt and Ga₂O₃ clusters confined in the 10MR channels of ZSM-5 can serve as a bifunctional catalyst for the direct ethane–benzene coupling reaction for the production of ethylbenzene, surpassing the performances of the counterpart catalysts made with PtGa nanoclusters and nanoparticles.

The development of robust NMR methodologies to probe dynamics on the atomic scale is vital to elucidate the close relations between structure, motion, and function in biological systems. Here, we present an automated protocol to measure, using magic-angle spinning NMR, the effective ¹³C–¹⁵N dipolar coupling constants between multiple spin pairs simultaneously with high accuracy. We use the experimental dipolar coupling constants to quantify the order parameters of multiple C–N bonds in the thousands of identical copies of the coat protein in intact fd-Y21M filamentous bacteriophage virus and describe its overall dynamics on the submillisecond time scale. The method is based on combining three pseudo three-dimensional NMR experiments, where a rotational echo double resonance (REDOR) dephasing block, designed to measure internuclear distances, is combined with three complementary ¹³C–¹³C mixing schemes: dipolar-assisted rotational resonance, through-bond transfer-based double quantum/single quantum correlation, and radio frequency driven recoupling. These mixing schemes result in highly resolved carbon spectra with correlations that are created by different transfer mechanisms. We show that the helical part of the coat protein undergoes a uniform small (∼30°) amplitude motion, while the N-terminus is highly flexible. In addition, our results suggest that the reduced mobility of lysine sidechains at the C-terminus are a signature of binding to the single stranded DNA.

The formation of a hexagonal diamond represents one of the most intriguing questions in materials science. Under shock conditions, the graphite basal plane tends to slide and pucker to form diamond. However, how the shock strength determines the phase selectivity remains unclear. In this work, using a DFT-trained carbon global neural network model, we studied the shock-induced graphite transition. The poor sliding caused by scarce sliding time under high-strength shock leads to metastable hexagonal diamond with an orientation relationship of (001)_G//(100)_HD+[010]_G//[010]_HD, while under low-strength shock due to long sliding distance cubic diamond forms with the orientation (001)_G//(111)_CD+[100]_G//[110]_CD, unveiling the strength-dependent graphite transition mechanism. We for the first time provide computational evidence of the strength-dependent graphite transition from first-principles, clarifying the long-term unresolved shock-induced hexagonal diamond formation mechanism and the structural source of the strength-dependent trend, which facilitates the hexagonal diamond synthesis via controlled experiment.

The electrochemical CO₂ reduction (eCO₂R) in membrane electrode assemblies (MEAs) has brought e-chemical production one step closer to commercialization because of its advantages of minimized ohmic resistance and stackability. However, the current performance of reported eCO₂R in MEAs is still far below the threshold for economic feasibility where low overall cell voltage (<2 V) and extensive stability (>5 years) are required. Furthermore, while the production cost of e-chemicals heavily relies on the carbon capture and product separation processes, these areas have received much less attention compared to CO₂ electrolysis, itself. In this perspective, we examine the current status of eCO₂R technologies from both academic and industrial points of view. We highlight the gap between current capabilities and commercialization standards and offer future research directions for eCO₂R technologies with the hope of achieving industrially viable e-chemical production.

Several enzymes from the metallo-β-lactamase-like family of lactonases (MLLs) degrade N-acyl L-homoserine lactones (AHLs). They play a role in a microbial communication system known as quorum sensing, which contributes to pathogenicity and biofilm formation. Designing quorum quenching (QQ) enzymes that can interfere with this communication allows them to be used in a range of industrial and biomedical applications. However, tailoring these enzymes for specific communication signals requires a thorough understanding of their mechanisms and the physicochemical properties that determine their substrate specificities. We present here a detailed biochemical, computational, and structural study of GcL, which is a highly proficient and thermostable MLL with broad substrate specificity. We show that GcL not only accepts a broad range of substrates but also hydrolyzes these substrates through at least two different mechanisms. Further, the preferred mechanism appears to depend on both the substrate structure and/or the nature of the residues lining the active site. We demonstrate that other lactonases, such as AiiA and AaL, show similar mechanistic promiscuity, suggesting that this is a shared feature among MLLs. Mechanistic promiscuity has been seen previously in the lactonase/paraoxonase PON1, as well as with protein tyrosine phosphatases that operate via a dual general acid mechanism. The apparent prevalence of this phenomenon is significant from both a biochemical and protein engineering perspective: in addition to optimizing for specific substrates, it may be possible to optimize for specific mechanisms, opening new doors not just for the design of novel quorum quenching enzymes but also of other mechanistically promiscuous enzymes.

The utilization of structure distortion to modulate the electronic structure and alter catalytic properties of metallic nanomaterials is a well-established practice, but accurately identifying and comprehensively understanding these distortions present significant challenges. Ligand-stabilized metal nanoclusters with well-defined structures serve as exemplary model systems to illustrate the structure chemistry of nanomaterials, among which few studies have investigated nanocluster models that incorporate structural distortions. In this work, a novel copper hydride nanocluster, Cu₄₂(PPh₃)₈(RS)₄(CF₃COO)₁₀(CH₃O)₄H₁₀ (Cu₄₂; PPh₃ is triphenylphosphine and RSH is 2,4-dichlorophenylthiol), with a highly twisted structure has been synthesized in a simple way. Structural analysis reveals Cu₄₂ comprises two Cu₂₅ units that are conjoined in a nearly orthogonal manner. The dramatic distortion in the metal framework, which is driven by multiple interactions from the surface ligands, endows the cluster with a rich array of uncoordinated metal sites on the surface. The resulting cluster, as envisioned, exhibits remarkable activity in catalyzing carbonylation of anilines. The findings from this study not only provides atomically precise insights into the structural distortions that are pertinent to nanoparticle catalysts but also underscores the potential of structurally distorted NCs as a burgeoning generation of catalysts with precise structures and outstanding performances that can be tailored for specific functions.