ChemBioChemPub Date : 2025-05-15DOI: 10.1002/cbic.202500329
Shuang Liu, Runmiao Yang, Jian Xu
{"title":"Photoinduced Ene-Reductase Catalysis via Electron Donor–Acceptor Complexes","authors":"Shuang Liu, Runmiao Yang, Jian Xu","doi":"10.1002/cbic.202500329","DOIUrl":"10.1002/cbic.202500329","url":null,"abstract":"<p>Flavin-dependent ene-reductases (EREDs) have emerged as powerful biocatalysts for the asymmetric reduction of various substrates. This review focuses on the recent advances in light-induced electron transfer and subsequent reduction reactions mediated by EREDs. Upon photoexcitation, the flavin cofactor transitions to an excited state, significantly enhancing its reduction potential. Mechanistic insights into how light activation alters the redox properties of EREDs are discussed, leading to more efficient catalysis. The review also highlights the broadened application scope of photoexcited EREDs in organic synthesis. Additionally, the challenges and future directions in optimizing these light-driven biocatalytic processes are explored. This overview provides a foundation for developing novel, light-controlled enzymatic systems with enhanced catalytic performance.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 14","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075147","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":"Amino Acid–Based Self-Assembled Supramolecular Structures: From Pathological Implications to Biomedical Applications","authors":"Pooja Sharma, Prabhjot Singh, Neelam, Nishima Wangoo","doi":"10.1002/cbic.202500228","DOIUrl":"10.1002/cbic.202500228","url":null,"abstract":"<p>Self-assembly is defined as a spontaneous ordering of molecules into distinct supramolecular structures similar to the naturally occurring biomolecules such as DNA, lipids, and proteins. Interestingly, this strategy has gained huge importance in recent decades, leading to substantial advancements in the biomedical field, including drug delivery, biosensing, tissue engineering, etc. The unique role of “FF” moiety in promoting self-aggregation in larger proteins is well established owing to its frequent occurrence in amyloids. This finding comes as a breakthrough in peptide nanotechnology research leading to the exploration of various peptide-based supramolecular structures demonstrating exceptional functional roles with futuristic applications. In this regard, since amino acids are the building blocks of peptides, the detailed investigation and discussion regarding their self-assembly behavior are expected to provide important insights into designing advanced functional materials from amino acids and peptides. This review provides a systematic overview of various latest findings on amino acid–based self-assembly and its pathological as well as functional role. The review also highlights the importance of emerging applications from self-assembled amino acid–based nanomaterials in the field of material science and biomedicine.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 13","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956062","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":"Photoactivatable Alkyne Tag for Photolabeling Biomolecules in Living Cells.","authors":"Yuki Umeda, Hao Zhu, Satoshi Yamaguchi, Sho Nakamura, Masato Takada, Shin Izuta, Akimitsu Okamoto","doi":"10.1002/cbic.202500190","DOIUrl":"10.1002/cbic.202500190","url":null,"abstract":"<p><p>Light-induced molecular imaging methods have attracted considerable attention owing to their potential for monitoring changes in the localization of intracellular molecules, which can provide valuable insights into the molecular mechanisms of living systems. In this article, a photoactivatable alkyne tag is developed by modifying an unstable intermediate of the alkyne-forming reaction with a photodegradable protecting group; the photodegradation triggers the conversion of the intermediate into a linear alkyne in an aqueous solution. The developed photoactivatable alkyne tag is incorporated into a cholesterol analog, introduced into living cells, and exposed to a biocompatible dose of 365 nm light. Subsequently, the cholesterol analog in light-irradiated cells is microscopically visualized through alkyne-specific biotinylation via copper-catalyzed azide-alkyne cycloaddition and biotin-specific labeling with fluorescence-labeled streptavidin. The obtained results indicate that the photoactivatable alkyne tag can be photoconverted into alkyne derivatives inside cells and applied to the light-induced intracellular imaging of biomolecules. This photoactivatable chemical tag can potentially expand the range of applications of light-induced molecular imaging of various biomolecules.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2500190"},"PeriodicalIF":2.6,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075146","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 : 2025-05-13DOI: 10.1002/cbic.202500055
Dawei Ji, Rebecca L. Frkic, Javad Delyami, Joachim S. Larsen, Matthew A. Spence, Colin J. Jackson
{"title":"A Thermostable Bacterial Metallohydrolase that Degrades Organophosphate Plasticizers","authors":"Dawei Ji, Rebecca L. Frkic, Javad Delyami, Joachim S. Larsen, Matthew A. Spence, Colin J. Jackson","doi":"10.1002/cbic.202500055","DOIUrl":"10.1002/cbic.202500055","url":null,"abstract":"<p>A cyclase-phosphotriesterase (C-PTE) from <i>Ruegeria pomeroyi</i> DSS-3 has recently been identified for its capacity to detoxify several organophosphate compounds. However, several aspects of this enzyme remain unexplored, such as its activity with industrial organophosphates, its molecular structure, and its thermostability. In this work, the crystal structure of C-PTE is reported, which is solved to 2.3 Å resolution, providing insight into the enzyme's mechanism of action, revealing a binuclear Zn<sup>2+</sup> active site and distant similarity to other phosphotriesterases from the amidohydrolase superfamily. It is shown that C-PTE catalyzes the hydrolysis of the OP plasticizers triphenyl phosphate (TPhP) and tris(2-chloropropyl) phosphate (TCPP), albeit with low efficiency, but not the sterically bulkier tri-<i>o</i>-tolyl phosphate (ToTP). Finally, it is demonstrated that, even though <i>Ruegeria pomeroyi</i> DSS-3 is not a thermophile, C-PTE exhibits remarkable thermostability and retains structure up to 90 °C. Overall, these findings advance the understanding of C-PTE, suggesting that it is a good candidate for engineering owing to its thermostability and that it could contribute to bioremediation strategies to reduce the impact of pollution by industrial organophosphates.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 11","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.202500055","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957507","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}
ChemBioChemPub Date : 2025-05-13DOI: 10.1002/cbic.202500242
Vineet Kumar Mishra, Rheal Towner, Juan Carlos Rodriguez-Lecompte, Marya Ahmed
{"title":"PCFT-Independent Cellular Uptake of Cyclic Cell-Penetrating Peptide-Conjugated Folic Acid","authors":"Vineet Kumar Mishra, Rheal Towner, Juan Carlos Rodriguez-Lecompte, Marya Ahmed","doi":"10.1002/cbic.202500242","DOIUrl":"10.1002/cbic.202500242","url":null,"abstract":"<p>Folic acid is an essential component of many metabolic processes, including the synthesis of nucleoproteins, purines, and pyrimidines, and is a recommended supplement to lower the incidence of various disorders. Folic acid and folate-loaded nanoparticles are extensively evaluated for sustained release and enhanced stability of the molecule; however, malfunctioning of proton-coupled folate transporters (PCFTs) present on the intestinal cells and subsequent folate deficiency remain a major issue in this context. This study provides the first demonstration where cell-penetrating peptide-conjugated folic acid mediates PCFT-independent folic acid permeabilization and intracellular bioavailability in vitro in the intestinal cells and macrophages. Cyclic-transactivating transcriptional activator (cTAT) folic acid conjugates are prepared by solid-phase peptide synthesis and are evaluated for the cellular uptake and bioavailability in the presence and absence of PCFT inhibitors. Compared with free folic acid that showed PCFT-mediated cellular uptake, cTAT-folic acid conjugates exhibited enhanced cellular uptake at all studied pH and improved intracellular bioavailability of the cargo, as was determined by dihydrofolate reductase (DHFR) assay. Folic acid and cTAT-folic acid conjugates also dampened the production of proinflammatory mediators in the presence of toxins in vitro in macrophage cell lines.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 13","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.202500242","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951597","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}
ChemBioChemPub Date : 2025-05-12DOI: 10.1002/cbic.202401052
Michael M. Shahid, Grace Hohman, Mohamed Eldeeb
{"title":"Fine-Tuning Ferroptosis by Modulating GPX4 and Its Potential in Mitigating Neuronal Degeneration in Parkinson′s Disease","authors":"Michael M. Shahid, Grace Hohman, Mohamed Eldeeb","doi":"10.1002/cbic.202401052","DOIUrl":"https://doi.org/10.1002/cbic.202401052","url":null,"abstract":"<p>The increasing prevalence of neurodegenerative diseases necessitates the development of novel approaches to study, diagnose, and treat these devastating disorders. Accordingly, there is a critical need to precisely address the gap in the biochemical and physiological mechanisms that underlie neurodegenerative diseases to promote advancements in therapeutic interventions. Parkinson's Disease (PD), the second most common neurodegenerative disorder after Alzheimer's, demands further research focused on unravelling the rather intricate molecular mechanisms that drive its progression upon different cell signaling cues. While alpha-synuclein aggregation and mitochondrial dysfunction are two cellular hallmarks of the molecular pathophysiology of PD, few drugs are currently in clinical trials for treatment of PD, which warrants further studies to identify new therapeutic molecular targets. Herein, we briefly highlight some of the reported roles of ferroptosis, a modality of cell death that is driven by iron-dependent phospholipid peroxidation, and its regulation by glutathione peroxidase 4 (GPX4). We discuss the interconnectedness between lipid peroxidation and GPX4 regulation in the context of molecular pathogenesis of PD. Future studies are imperative in investigating the physiological role of ferroptosis and the translational impact of ferroptosis-specific modulators in studying PD biology.</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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143938892","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 : 2025-05-12DOI: 10.1002/cbic.202580904
Dr. Makoto Hashimoto, Dr. Kazuki Ishikawa, Yuri Fukushima, Sarina Shimazu, Mizuha Yabuzaki, Yuka Kamezawa, Dr. Takaaki Taguchi, Prof. Dr. Koji Ichinose
{"title":"Cover Feature: Characterization of ActVI-ORF3 and ActVI-ORF4 as Lactonizing and Delactonizing Enzymes in Relation to Metabolic Flux in Actinorhodin Biosynthesis (ChemBioChem 9/2025)","authors":"Dr. Makoto Hashimoto, Dr. Kazuki Ishikawa, Yuri Fukushima, Sarina Shimazu, Mizuha Yabuzaki, Yuka Kamezawa, Dr. Takaaki Taguchi, Prof. Dr. Koji Ichinose","doi":"10.1002/cbic.202580904","DOIUrl":"https://doi.org/10.1002/cbic.202580904","url":null,"abstract":"<p>The front cover shows the biosynthetic pathway of actinorhodin (ACT), a tricyclic dimer polyketide. ACT is biosynthesized from malonyl-CoA units by multiple enzymes (blue arrow) via monomeric DHK-OH. Intracellular ACT and DHK-OH are converted into their lactone-forms (yellow arrow) diffusible outside the cell. ActVI-ORF4 can reducibly delactonize KAL-OH to DHK-OH (green arrow), but not γ-ACT. Therefore, these two enzymes could appear to efficiently regulate metabolic flux in ACT biosynthesis. More details can be found in article 10.1002/cbic.202500049 by Makoto Hashimoto, Koji Ichinose, and co-workers.<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.202580904","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143938846","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}
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":"10.1002/cbic.202500193","url":null,"abstract":"<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, 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 are outlined. Further persistent challenges and outline possible refinements are discussed, highlighting how further innovations can expand PE's utility across diverse areas of research, biotechnology, and potential therapeutic interventions.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 12","pages":""},"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}