Communications Chemistry最新文献_第3页

Chemoenzymatic synthesis.

IF 5.9 2区化学

Communications Chemistry Pub Date : 2025-03-13 DOI: 10.1038/s42004-025-01451-z

Paweł Borowiecki, Sandy Schmidt

引用次数: 0

Rational engineering of a thermostable α-oxoamine synthase biocatalyst expands the substrate scope and synthetic applicability.

IF 5.9 2区化学

Communications Chemistry Pub Date : 2025-03-13 DOI: 10.1038/s42004-025-01448-8

Ben Ashley, Sam Mathew, Mariyah Sajjad, Yaoyi Zhu, Nikita Novikovs, Arnaud Baslé, Jon Marles-Wright, Dominic J Campopiano

{"title":"Rational engineering of a thermostable α-oxoamine synthase biocatalyst expands the substrate scope and synthetic applicability.","authors":"Ben Ashley, Sam Mathew, Mariyah Sajjad, Yaoyi Zhu, Nikita Novikovs, Arnaud Baslé, Jon Marles-Wright, Dominic J Campopiano","doi":"10.1038/s42004-025-01448-8","DOIUrl":"10.1038/s42004-025-01448-8","url":null,"abstract":"Carbon-carbon bond formation is one of the key pillars of organic synthesis. Green, selective and efficient biocatalytic methods for such are therefore highly desirable. The α-oxoamine synthases (AOSs) are a class of pyridoxal 5'-phosphate (PLP)-dependent, irreversible, carbon-carbon bond-forming enzymes, which have been limited previously by their narrow substrate specificity and requirement of acyl-CoA thioester substrates. We recently characterized a thermophilic enzyme from Thermus thermophilus (ThAOS) with a much broader substrate scope and described its use in a chemo-biocatalytic cascade process to generate pyrroles in good yields and timescales. Herein, we report the structure-guided engineering of ThAOS to arrive at variants able to use a greatly expanded range of amino acid and simplified N-acetylcysteamine (SNAc) acyl-thioester substrates. The crystal structure of the improved ThAOS V79A variant with a bound PLP:L-penicillamine external aldimine ligand, provides insight into the properties of the engineered biocatalyst.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":"8 1","pages":"78"},"PeriodicalIF":5.9,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Stabilization of a miniprotein fold by an unpuckered proline surrogate.

IF 5.9 2区化学

Communications Chemistry Pub Date : 2025-03-12 DOI: 10.1038/s42004-025-01474-6

Madison M Wright, Benjamin H Rajewski, Taylor A Gerrein, Zhiyi Xu, Lorna J Smith, W Seth Horne, Juan R Del Valle

{"title":"Stabilization of a miniprotein fold by an unpuckered proline surrogate.","authors":"Madison M Wright, Benjamin H Rajewski, Taylor A Gerrein, Zhiyi Xu, Lorna J Smith, W Seth Horne, Juan R Del Valle","doi":"10.1038/s42004-025-01474-6","DOIUrl":"10.1038/s42004-025-01474-6","url":null,"abstract":"The unique role of proline in modulating protein folding and recognition makes it an attractive target for substitution to generate new proteomimetics. The design, synthesis, and conformational analysis of non-canonical surrogates can also aid in parsing the role of prolyl stereoelectronic effects on structure. We recently described the synthesis and conformational analysis of dehydro-δ-azaproline (ΔaPro), a novel unsaturated analogue of proline featuring a planar dehydropyrazine ring. When incorporated into host sequences, this backbone N-aminated proline surrogate forms an acylhydrazone bond with an unusually high trans rotamer bias and low isomerization barrier. Here, we used CD, NMR spectroscopy, and MD simulations to evaluate the impact of ΔaPro substitution within the polyproline II (PPII) and loop regions of the avian pancreatic polypeptide (aPP). The ΔaPro residue strongly favors PPII conformation and stabilizes the aPP tertiary fold when incorporated at select positions within the miniprotein. A variant featuring three ΔaPro substitutions was found to significantly enhance the thermal stability of wild-type aPP despite compromising protein dimerization. Our results suggest that the stability of proline-rich folds relies more on backbone torsional preferences than ring puckering and informs strategies for the incorporation of ΔaPro into thermally stable and functional proteomimetics.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":"8 1","pages":"76"},"PeriodicalIF":5.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11904010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

XFEL crystallography reveals catalytic cycle dynamics during non-native substrate oxidation by cytochrome P450BM3.

IF 5.9 2区化学

Communications Chemistry Pub Date : 2025-03-12 DOI: 10.1038/s42004-025-01440-2

Satoshi Nagao, Wako Kuwano, Takehiko Tosha, Keitaro Yamashita, Joshua Kyle Stanfield, Chie Kasai, Shinya Ariyasu, Kunio Hirata, Go Ueno, Hironori Murakami, Hideo Ago, Masaki Yamamoto, Osami Shoji, Hiroshi Sugimoto, Minoru Kubo

{"title":"XFEL crystallography reveals catalytic cycle dynamics during non-native substrate oxidation by cytochrome P450BM3.","authors":"Satoshi Nagao, Wako Kuwano, Takehiko Tosha, Keitaro Yamashita, Joshua Kyle Stanfield, Chie Kasai, Shinya Ariyasu, Kunio Hirata, Go Ueno, Hironori Murakami, Hideo Ago, Masaki Yamamoto, Osami Shoji, Hiroshi Sugimoto, Minoru Kubo","doi":"10.1038/s42004-025-01440-2","DOIUrl":"10.1038/s42004-025-01440-2","url":null,"abstract":"Cytochrome P450s are haem-containing enzymes, catalysing the regio- and stereospecific oxidation of non-activated hydrocarbons. Among these, the bacterial P450BM3 is a promising biocatalyst due to its high enzymatic activity. Given the significant conformational flexibility of this enzyme, understanding protein-substrate interactions and associated structural dynamics are crucial for designing P450BM3-based biocatalysts. Herein, employing an X-ray free electron laser in combination with freeze-trap crystallography and spectroscopy techniques, we captured the intact structures of engineered P450BM3s in the initial stages of catalysis during styrene epoxidation, in the presence of a decoy molecule. We found that the iron reduction significantly altered the active-site orientation of styrene, driven by structural changes in surrounding helices and hydrogen-bonding networks. Oxygen binding to iron further stabilised its productive orientation, providing a molecular basis for the experimentally observed enzyme kinetics and enantioselectivities. This study reveals the substrate dynamics of a P450 enzyme, showcasing how changes in haem chemistry affect enzyme structure and substrate orientation.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":"8 1","pages":"63"},"PeriodicalIF":5.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11903658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ca²⁺-triggered allosteric catalysts crosstalk with cellular redox systems through their foldase- and reductase-like activities.

IF 5.9 2区化学

Communications Chemistry Pub Date : 2025-03-11 DOI: 10.1038/s42004-025-01466-6

Rumi Mikami, Yuhei Sato, Shingo Kanemura, Takahiro Muraoka, Masaki Okumura, Kenta Arai

{"title":"Ca2+-triggered allosteric catalysts crosstalk with cellular redox systems through their foldase- and reductase-like activities.","authors":"Rumi Mikami, Yuhei Sato, Shingo Kanemura, Takahiro Muraoka, Masaki Okumura, Kenta Arai","doi":"10.1038/s42004-025-01466-6","DOIUrl":"10.1038/s42004-025-01466-6","url":null,"abstract":"Effective chemical catalysts can artificially control intracellular metabolism. However, in conventional catalytic chemistry, activity and cytotoxicity have a trade-off relationship; thus, driving catalysts in living cells remains challenging. To overcome this critical issue at the interface between catalytic chemistry and biology, we developed cell-driven allosteric catalysts that exert catalytic activity at specific times. The synthesized allosteric redox catalysts up- and downregulated their foldase- and antioxidase-like activities in response to varying Ca2+ concentrations, which is a key factor for maintenance of the redox status in cells. In the absence of Ca2+ or at low Ca2+ concentrations, the compounds were mostly inactive and hence did not affect cell viability. In contrast, under specific conditions with elevated cytosolic Ca2+ concentrations, the activated compounds resisted the redox imbalance induced by the reactive oxygen species generated by Ca2+-stimulated mitochondria. Smart catalysts that crosstalk with biological phenomena may provide a platform for new prodrug development guidelines.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":"8 1","pages":"74"},"PeriodicalIF":5.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11897157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bile acid derivatives as novel co-adsorbents for enhanced performance of blue dye-sensitized solar cells. 胆汁酸衍生物作为新型共吸附剂用于提高蓝色染料敏化太阳能电池的性能。

IF 5.9 2区化学

Communications Chemistry Pub Date : 2025-03-10 DOI: 10.1038/s42004-025-01433-1

Kezia Sasitharan, Allan J Mora Abarca, Fabio Cucinotta, Leslie W Pineda, Victor Hugo Soto Tellini, Marina Freitag

{"title":"Bile acid derivatives as novel co-adsorbents for enhanced performance of blue dye-sensitized solar cells.","authors":"Kezia Sasitharan, Allan J Mora Abarca, Fabio Cucinotta, Leslie W Pineda, Victor Hugo Soto Tellini, Marina Freitag","doi":"10.1038/s42004-025-01433-1","DOIUrl":"10.1038/s42004-025-01433-1","url":null,"abstract":"Diketopyrrolopyrrole-based blue dyes in dye-sensitized solar cells (DSCs) exhibit promise for building-integrated photovoltaics, but their efficiency is compromised by dye aggregation-induced charge recombination. Novel bile acid derivative co-adsorbents featuring bulky hydrophobic substituents at the 3-β position were synthesized to address this challenge. These molecules, designed to modulate intermolecular electronic interactions, effectively altered the TiO2 surface coverage dynamics, as evidenced by UV-Vis spectroscopy and dye-loading kinetics. Systematic variation of hydrophilic substituents revealed structure-function relationships in dye separation efficacy. Devices incorporating these co-adsorbers achieved power conversion efficiencies (PCE) of 7.6%, surpassing reference devices (5.2%) and those using conventional chenodeoxycholic acid co-adsorbers (6.4%). The optimized devices exhibited a 30% increase in short-circuit current density, 30 mV enhancement in open-circuit voltage, and 60% peak external quantum efficiency at 550 nm. Time-resolved photoluminescence spectroscopy confirmed suppressed non-radiative recombination, while transient absorption spectroscopy revealed accelerated electron injection rates from 6.4 ps to 4.6 ps. Electrochemical impedance spectroscopy elucidated the mechanism of reduced interfacial recombination. These findings present a molecular engineering strategy for mitigating lateral charge transfer in planar dye systems, advancing semi-transparent hybrid photovoltaics.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":"8 1","pages":"75"},"PeriodicalIF":5.9,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11894181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Isoaspartate-containing galanin in rat hypothalamus.

IF 5.9 2区化学

Communications Chemistry Pub Date : 2025-03-08 DOI: 10.1038/s42004-025-01475-5

Samuel Okyem, David H Mast, Elena V Romanova, Stanislav S Rubakhin, Jonathan V Sweedler

{"title":"Isoaspartate-containing galanin in rat hypothalamus.","authors":"Samuel Okyem, David H Mast, Elena V Romanova, Stanislav S Rubakhin, Jonathan V Sweedler","doi":"10.1038/s42004-025-01475-5","DOIUrl":"10.1038/s42004-025-01475-5","url":null,"abstract":"The isoaspartate residue is a spontaneous, time-dependent post-translational modification (PTM) of proteins and peptides, associated with in vivo protein aggregation and changes in molecule lifetime. While this is considered a slow modification impacting long lived proteins, surprisingly, we observed this PTM at high levels within the relatively short-lived neuropeptide galanin (Gal). The combination of liquid chromatography-trapped ion mobility mass spectrometry and protein Isoaspartyl methyltransferase assays demonstrated that 20 ± 2% of the mature Gal contain L-Isoaspartate residue in the hypothalamus of Rattus norvegicus. Aspartate in Gal isomerizes spontaneously under mildly acidic conditions within 48 h in vitro, much faster than previously assumed. Gal with the L-isoaspartate PTM significantly enhanced fibril formation. Transmission electron microscopy revealed differences in morphology of fibrils formed by D17Isoasparte Gal compared to the unmodified peptide. Observed characteristics of D17Isoasparte Gal suggest a potential mechanism for the development of in vivo Gal fibril deposits previously reported in the brain.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":"8 1","pages":"72"},"PeriodicalIF":5.9,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Oxygen reduction kinetics of high performance BaCo_0.4Fe_0.4M_0.1Y_0.1O_3-δ (M = Mg, Zr) positrode for protonic ceramic fuel cells.

IF 5.9 2区化学

Communications Chemistry Pub Date : 2025-03-08 DOI: 10.1038/s42004-025-01468-4

Hirofumi Sumi, Konosuke Watanabe, Aman Sharma, Masaya Fujioka, Hiroyuki Shimada, Yasunobu Mizutani, Md Saiful Alam, Isao Kagomiya

{"title":"Oxygen reduction kinetics of high performance BaCo0.4Fe0.4M0.1Y0.1O3-δ (M = Mg, Zr) positrode for protonic ceramic fuel cells.","authors":"Hirofumi Sumi, Konosuke Watanabe, Aman Sharma, Masaya Fujioka, Hiroyuki Shimada, Yasunobu Mizutani, Md Saiful Alam, Isao Kagomiya","doi":"10.1038/s42004-025-01468-4","DOIUrl":"10.1038/s42004-025-01468-4","url":null,"abstract":"Protonic ceramic fuel cells (PCFCs) should exhibit high performance at intermediate temperatures in the range of 400-600 °C. To reduce the operating temperature, more active air electrodes (positrodes) are needed. In the present work, BaCo0.4Fe0.4Mg0.1Y0.1O3-δ (BCFMY) is investigated as a positrode material for application in PCFCs as well as solid oxide fuel cells (SOFCs). For SOFCs, the polarization resistance ascribed to the oxygen reduction reaction is proportional to pO2-1/4 (pO2: oxygen partial pressure), suggesting that the rate-determining process is the charge transfer on the mixed ionic-electronic conductors. For PCFCs, this polarization resistance is proportional to pO2-1/2, suggesting that the rate-determining process is the oxygen dissociation. The total polarization resistance for the PCFCs using the BCFMY positrode is 0.066 Ωcm2 at 600 °C, lower than that using the BaCo0.4Fe0.4Zr0.1Y0.1O3-δ (BCFZY) positrode. The higher oxygen nonstoichiometry of BCFMY promotes the oxygen dissociation process on the PCFC positrode surface.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":"8 1","pages":"71"},"PeriodicalIF":5.9,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chemical linkers switch triglycerol detergents from bacterial protein purification to mild antibiotic amplification.

IF 5.9 2区化学

Communications Chemistry Pub Date : 2025-03-08 DOI: 10.1038/s42004-025-01477-3

Abhishek Kumar Singh, Marc Seewald, Boris Schade, Christian Zoister, Rainer Haag, Leonhard Hagen Urner

{"title":"Chemical linkers switch triglycerol detergents from bacterial protein purification to mild antibiotic amplification.","authors":"Abhishek Kumar Singh, Marc Seewald, Boris Schade, Christian Zoister, Rainer Haag, Leonhard Hagen Urner","doi":"10.1038/s42004-025-01477-3","DOIUrl":"10.1038/s42004-025-01477-3","url":null,"abstract":"Non-ionic detergents enable the investigation of cell membranes, including biomolecule purification and drug delivery. The question of whether non-ionic detergents associated with satisfying protein yields following extraction and affinity purification of proteins from lysed E. coli membranes can amplify antibiotics on whole-cell E. coli remains to be addressed. We unlock the modular chemistry of linear triglycerol detergents to reveal that more polar, non-ionic detergents that form globular micelles work better in amplifying antimicrobial activities of antibiotics than in purifying the membrane proteins mechanosensitive channel and aquaporin Z. Less polar detergents that form worm-like micelles indicate poor performances in both applications. With chromatography we demonstrate how fine-tuning the polarity of chemical linkers between detergent headgroups and tails can switch the utility of detergents from protein purification to antibiotic amplification. We anticipate our findings to be a starting point for structure-property studies to better understand detergent designs in supramolecular chemistry and membrane research.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":"8 1","pages":"70"},"PeriodicalIF":5.9,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

C(sp³)-heteroatom bond formation by iron-catalyzed soft couplings.

IF 5.9 2区化学

Communications Chemistry Pub Date : 2025-03-08 DOI: 10.1038/s42004-025-01478-2

Julius Semenya, Yuanjie Yang, Hye Joon Lee, Kimberly A Giannantonio, Rikhil Manduva, Elias Picazo

{"title":"C(sp3)-heteroatom bond formation by iron-catalyzed soft couplings.","authors":"Julius Semenya, Yuanjie Yang, Hye Joon Lee, Kimberly A Giannantonio, Rikhil Manduva, Elias Picazo","doi":"10.1038/s42004-025-01478-2","DOIUrl":"10.1038/s42004-025-01478-2","url":null,"abstract":"Carbon-heteroatom bonds are of great importance due to their prevalence in pharmaceuticals, agrochemicals, materials, and natural products. Despite the effective use of metal-catalyzed cross-coupling reactions between sp2-hybridized organohalides and soft heteroatomic nucleophiles for carbon-heteroatom bond formation, the use of sp3-hybridized organohalides remain limited and the coupling with thiols remains elusive. Here, we report the coupling of sp3-hybridized benzyl or tertiary halides with soft thiol nucleophiles catalyzed by iron and extend the utility to alcohol and amine nucleophiles. The reaction is broad in substrate scope for both coupling partners and applicable in the construction of congested tri- and tetrasubstituted carbon centers as well as β-quaternary heteroatomic products. The synthetic utility is further emphasized by gram-scale synthesis and rapid herbicide library synthesis. Overall, we provide an efficient method to prepare pharmaceutically and materially relevant carbon-heteroatom bonds by expanding iron-catalyzed cross-coupling reactions to the coupling of sp3-hybridized organohalides with soft nucleophiles.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":"8 1","pages":"73"},"PeriodicalIF":5.9,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0