ChemBioChemPub Date : 2025-05-12DOI: 10.1002/cbic.202580901
Pierre Nicolas Bizat, Nazarii Sabat, Marcel Hollenstein
{"title":"Front Cover: Recent Advances in Biocatalytic and Chemoenzymatic Synthesis of Oligonucleotides (ChemBioChem 9/2025)","authors":"Pierre Nicolas Bizat, Nazarii Sabat, Marcel Hollenstein","doi":"10.1002/cbic.202580901","DOIUrl":"https://doi.org/10.1002/cbic.202580901","url":null,"abstract":"<p>Access to synthetic oligonucleotides is crucial for applications in diagnostics, therapeutics, synthetic biology, and nanotechnology. Traditional solid phase synthesis is limited by sequence length and complexities, low yields, high costs and poor sustainability. Similarly, polymerase-based approaches do not permit any control on the positioning of modifications and display poor substrate tolerance. In response, biocatalytic and chemoenzymatic strategies have emerged as promising alternatives, offering selective and efficient pathways for oligonucleotide synthesis. These methods leverage the precision and efficiency of enzymes to construct oligonucleotides with high fidelity. More details can be found in article 10.1002/cbic.202400987 by Pierre Nicolas Bizat, Nazarii Sabat, and Marcel Hollenstein.<figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 9","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.202580901","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143938845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Advancement of Prime Editing Technology.","authors":"Lu Zhang, Dongdong Zhao, Zhandong Wei, Xiao Zhu, Taixin Sha, Wenzhu Tang, Changhao Bi, Xueli Zhang","doi":"10.1002/cbic.202500193","DOIUrl":"https://doi.org/10.1002/cbic.202500193","url":null,"abstract":"<p><p>The advent of CRISPR/Cas genome editing has spurred major breakthroughs across life sciences, offering vast potential across numerous research and application fields. Among the expanding toolkit of CRISPR/Cas-derived methods, prime editing (PE) stands out for its versatility and specificity, enabling precise point mutations and small insertions or deletions without requiring double-stranded DNA breaks. Since its introduction, PE has undergone multiple rounds of optimization to improve performance. In this review, we first outline the core components and mechanism of prime editors, followed by four key evolution strategies: protein engineering, pegRNA modifications, accessory protein recruitment, and paired pegRNA approaches. We then discuss persistent challenges and outline possible refinements, highlighting how further innovations can expand prime editing's utility across diverse areas of research, biotechnology, and potential therapeutic interventions.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500193"},"PeriodicalIF":2.6,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Tagatose 1,6-bisphosphate aldolases, the unloved DHAP-aldolases.","authors":"Christine Guérard-Hélaine, Léo Paulat, Marielle Lemaire, Virgil Hélaine","doi":"10.1002/cbic.202500285","DOIUrl":"https://doi.org/10.1002/cbic.202500285","url":null,"abstract":"<p><p>Tagatose-1,6-bisphosphate aldolases (TagA) have been understudied. The limited publications on the subject report a poor stereoselectivity, which quickly led to their classification among the less interesting aldolases. This conclusion, which appeared inadequate, discouraged further investigation by other researchers. The objective here is to re-examine all these studies in detail to finally uncover inconsistencies and unexplained observations regarding the behaviour of these enzymes. Ultimately, there is a significant lack of research that could deepen our understanding of TagA, which would likely reveal its potential to be as valuable as its counterparts: fructose-1,6-bisphosphate, rhamnulose-1-phosphate, and fuculose-1-phosphate aldolases.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500285"},"PeriodicalIF":2.6,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChemBioChemPub Date : 2025-05-10DOI: 10.1002/cbic.202500251
Zehui Duan, Jiaao Wei, Stephen B Carr, Miguel Ramirez, Rhiannon M Evans, Philip A Ash, Patricia Rodriguez-Macia, Amit Sachdeva, Kylie Alison Vincent
{"title":"Cyanophenylalanine as an Infrared Probe for Iron-Sulfur Cluster Redox State in Multi-Centre Metalloenzymes.","authors":"Zehui Duan, Jiaao Wei, Stephen B Carr, Miguel Ramirez, Rhiannon M Evans, Philip A Ash, Patricia Rodriguez-Macia, Amit Sachdeva, Kylie Alison Vincent","doi":"10.1002/cbic.202500251","DOIUrl":"https://doi.org/10.1002/cbic.202500251","url":null,"abstract":"<p><p>We demonstrate that the noncanonical amino acid, para-cyanophenylalanine (CNF), when incorporated into metalloproteins, functions as an infrared spectroscopic probe for the redox state of iron sulfur clusters, offering a strategy for determining electron occupancy in the electron transport chains of complex metalloenzymes. We observe a redshift of ≈ 1 - 2 cm-1 in the NC stretching frequency following reduction of spinach ferredoxin modified to contain CNF close to its [2Fe-2S] centre, and this shift is reversed on re-oxidation. We extend this to CNF positioned near to the proximal [4Fe-4S] cluster of the [FeFe] hydrogenase from Desulfovibrio desulfuricans. In combination with a distal [4Fe-4S] cluster and the [4Fe-4S] cluster of the active site 'H-cluster' ([4Fe-4S]H), the proximal cluster forms an electron relay connecting the active site to the surface of the protein. Again, we observe a reversible shift in wavenumber for CNF following cluster reduction in either apo-protein (containing the iron-sulfur clusters but lacking the active site) or holo-protein with intact active site, demonstrating general applicability of this approach to studying complex metalloenzymes.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500251"},"PeriodicalIF":2.6,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChemBioChemPub Date : 2025-05-09DOI: 10.1002/cbic.202500152
Aishi Chakrabarti, Charity S G Ganskow, Mervic D Kagho, Claire C Jimidar, Lorenz Wiese, Neslihan Beyazit, Ulrike Beutling, Magarita Seeger, Silvana Smits, Stella Nyström, Anett Schallmey, Anne Farewell, Mark Brönstrup, Philipp Klahn
{"title":"Synthesis and evaluation of pseudoglucosinolates (psGSLs) releasing isothiocyanates (ITCs) in the presence of azoreductases.","authors":"Aishi Chakrabarti, Charity S G Ganskow, Mervic D Kagho, Claire C Jimidar, Lorenz Wiese, Neslihan Beyazit, Ulrike Beutling, Magarita Seeger, Silvana Smits, Stella Nyström, Anett Schallmey, Anne Farewell, Mark Brönstrup, Philipp Klahn","doi":"10.1002/cbic.202500152","DOIUrl":"https://doi.org/10.1002/cbic.202500152","url":null,"abstract":"<p><p>Naturally occurring isothiocyanates (ITCs) display multiple interesting bioactivities, but their medicinal exploitation is very limited as ITCs are non-druglike compounds with problematic pharmacokinetic properties. The concept of pseudoglucosinolates (psGSLs) provides a novel prodrug approach for the release of ITCs which can be adjusted to different triggers such as enzymatic and chemical microenvironments. Here, we report the first adaptation of this concept towards the release of ITCs in the presence of azoreductases within a turn-on fluorescence probe and underline its applicability in covalent protein labelling.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500152"},"PeriodicalIF":2.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hydrocarbon stapling enables improvement of antimicrobial activity and proteolytic stability of host-defense peptide ocellatin-3N.","authors":"Hao Yang, Fei Yuan, Guangxu Xie, Yinxue Fu, Jia Mi, Longjie Yu, Weijia Liu, Yulei Li","doi":"10.1002/cbic.202500204","DOIUrl":"https://doi.org/10.1002/cbic.202500204","url":null,"abstract":"<p><p>Ocellatin-3N is a cationic, amphiphilic host-defense peptide with 19 residues, which was isolated from the Caribbean frog Leptodactylus nesiotus. Its analogue Oce-3N-0 shows potent inhibitory activity against both Gram-negative and Gram-positive pathogens, and has great potential as a broad-spectrum antimicrobial agent. However, the application of Oce-3N-0 as an antimicrobial agent is limited due to its both unstable structure and susceptibility to degradation by proteases. In this research, a series of hydrocarbon-stable analogs of Oce-3N-0 were synthesized and evaluated for their chemical and biological properties to improve potential application of Oce-3N-0 in the field of antimicrobial drug development. Some analogs showed remarkable improvement not only in protease resistance, but also in antimicrobial activity when compared to the parent peptide. In particular, the stapled peptide Oce-3N-5 showed promising prospects for novel antimicrobial drug development. This study can provide a reference for the development of antimicrobial drugs.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500204"},"PeriodicalIF":2.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChemBioChemPub Date : 2025-05-09DOI: 10.1002/cbic.202500315
Carsten Wieder, Rainer Wiechert, Alexander Yemelin, Louis Pergaud Sandjo, Eckhard Thines, Till Opatz, Anja Schüffler
{"title":"Biosynthesis of the fungal cyclic lipodepsipeptide pleosporacin, a new selective inhibitor of the phytopathogen Botrytis cinerea.","authors":"Carsten Wieder, Rainer Wiechert, Alexander Yemelin, Louis Pergaud Sandjo, Eckhard Thines, Till Opatz, Anja Schüffler","doi":"10.1002/cbic.202500315","DOIUrl":"https://doi.org/10.1002/cbic.202500315","url":null,"abstract":"<p><p>Bioactivity-guided isolation led to the identification of the cyclic lipodepsipeptide pleosporacin (1) from the mycelia extract of fungal strain Pleosporales sp. IBWF 020-21, a potent selective inhibitor of the fungal phytopathogen Botrytis cinerea. The structure and stereochemistry of 1 were elucidated by NMR and Marfey analysis, respectively. Genome mining identified a candidate biosynthetic gene cluster encoding a hexamodular NRPS, PleA, a fatty acyl-AMP ligase, PleB, and an aspartate decarboxylase, PleC. Reconstitution of pleABC allowed for heterologous production of 1 in Aspergillus oryzae and confirmed the identity of the ple cluster. Based on our findings we propose a biosynthetic route, with PleB catalyzing lipoinitiation and PleC providing the non-proteinogenic amino acid β-alanine for the assembly of 1.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500315"},"PeriodicalIF":2.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Gas Microbubble Formation via Near-Infrared Femtosecond Laser Ablation in Live Cells.","authors":"Kazunori Okano, Rieko Aida, Hayato Suwa, Naomi Tanga, Koichro Kishima, Yaxiaer Yalikun, Yoichroh Hosokawa, Hiromi Hagiwara","doi":"10.1002/cbic.202500086","DOIUrl":"https://doi.org/10.1002/cbic.202500086","url":null,"abstract":"<p><p>Focused near-infrared femtosecond (NIR fs) laser irradiation induces efficient photochemical breakdown of intracellular molecules, resulting in the formation of gas microbubbles that ultimately lead to cell death and removal. This study characterizes these microbubbles using high-speed imaging. Microbubbles generated within cells by single-pulse irradiation were consistently larger than those formed in the surrounding culture medium across a broad pulse energy range. Notably, the energy threshold for intracellular microbubble formation was several tens of nanojoules lower than in the culture medium, enabling precise cell ablation without inducing extracellular bubbling. Repeated pulse irradiation at 1 kHz frequency further reduced the energy threshold and increased bubble size, with saturation observed after approximately 30 pulses. Near-threshold pulse irradiation was then employed to develop a precise method for investigating cellular motility in vitro. Cell-free zones were created within cell monolayers, enabling motile cells to migrate into the cleared zones. This method was validated using the A549 lung cancer cell line and the plant flavonoid apigenin, which exhibited dose-dependent reduction in A549 cell motility. These findings highlight the method's potential for evaluating cellular behaviours and screening chemical compounds.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500086"},"PeriodicalIF":2.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChemBioChemPub Date : 2025-05-08DOI: 10.1002/cbic.202500004
Sariah Giraldo-Narcizo, Antonio Guerrero, Ana Maria Sanchez-Perez
{"title":"Ultraviolet Ozone Pretreatment Enhances selective PETase Biodegradation of Textiles Compared to Sunlight and Alkali Treatments.","authors":"Sariah Giraldo-Narcizo, Antonio Guerrero, Ana Maria Sanchez-Perez","doi":"10.1002/cbic.202500004","DOIUrl":"https://doi.org/10.1002/cbic.202500004","url":null,"abstract":"<p><p>The rapid growth of the fashion industry has led to increasing textile waste, exacerbating environmental pollution and climate change. To support sustainability and circular economy goals, this study investigates the enzymatic degradation of cotton/polyethylene terephthalate (PET) mixed textiles using PETase, comparing wild-type (WT) and mutant (MUT S238F/W159H) variants. To improve enzyme accessibility, we evaluated three pretreatment strategies: alkali treatment, ultraviolet-ozone (UVO) exposure, and natural sunlight weathering. The effects were assessed by measuring textile weight loss, surface morphology (SEM), infrared spectroscopy (FTIR), and yields of terephthalic acid (TPA) and mono-(2-hydroxyethyl) terephthalic acid (MHET). Alkali treatment produced the highest weight loss, while UVO pretreatment moderately degraded textiles and significantly enhanced enzymatic TPA production. In contrast, prolonged sunlight exposure had negligible effects. ^1H NMR analysis of supernatants confirmed the formation of oxidized PET products following UVO exposure, indicating surface chemical modifications that increase enzymatic susceptibility. Our results reveal differential effects on PET and cotton fibers, highlighting UVO as a promising, selective pretreatment for mixed textile waste. This study demonstrates the potential of combining photochemical oxidation and enzymatic processes for targeted PET degradation, contributing to more efficient textile recycling strategies.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500004"},"PeriodicalIF":2.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChemBioChemPub Date : 2025-05-08DOI: 10.1002/cbic.202500347
Sophie R Thomas, Riccardo Bonsignore
{"title":"Harnessing Organometallic Gold(III) Complexes as Precision Scaffolds for Next-Generation Therapeutic and Imaging Agents.","authors":"Sophie R Thomas, Riccardo Bonsignore","doi":"10.1002/cbic.202500347","DOIUrl":"https://doi.org/10.1002/cbic.202500347","url":null,"abstract":"<p><p>Gold(III) organometallic complexes, particularly cyclometalated Au(III) compounds, have emerged as powerful tools in catalysis and bioinorganic chemistry, offering unique reactivity distinct from their Au(I) counterparts. Among their most interesting transformations, C-S cross-coupling reactions have become a selective strategy for cysteine arylation, enabling site-specific modifications of peptides and proteins. This review provides a comprehensive overview of cyclometalated Au(III) complexes in C-S bond formation, detailing the mechanistic insights, ligand effects, and electronic factors that dictate their reactivity. The role of ancillary ligands in tuning stability and selectivity is critically assessed, alongside advancements in structural modifications that enhance catalytic efficiency. Beyond fundamental C-S cross-coupling, we explore the broader applications of these gold(III) complexes, including enzyme inhibition, metabolic disruption, and transmembrane protein modulation, with implications in anticancer therapy, antimicrobial strategies, and in vivo catalytic transformations. By bridging fundamental organometallic reactivity with innovative biomedical applications, this review highlights the potential of cyclometalated Au(III) complexes as next-generation catalysts for both synthetic and therapeutic innovations.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500347"},"PeriodicalIF":2.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}