{"title":"Multinuclear non-heme iron dependent oxidative enzymes (MNIOs) involved in unusual peptide modifications","authors":"Jeff Y. Chen, Wilfred A. van der Donk","doi":"10.1016/j.cbpa.2024.102467","DOIUrl":"https://doi.org/10.1016/j.cbpa.2024.102467","url":null,"abstract":"<div><p>Multinuclear non-heme iron dependent oxidative enzymes (MNIOs), formerly known as domain of unknown function 692 (DUF692), are involved in the post-translational modification of peptides during the biosynthesis of peptide-based natural products. These enzymes catalyze highly unusual and diverse chemical modifications. Several class-defining features of this large family (>14 000 members) are beginning to emerge. Structurally, the enzymes are characterized by a TIM-barrel fold and a set of conserved residues for a di- or tri–iron binding site. They use molecular oxygen to modify peptide substrates, often in a four-electron oxidation taking place at a cysteine residue. This review summarizes the current understanding of MNIOs. Four modifications are discussed in detail: oxazolone-thioamide formation, β-carbon excision, hydantoin-macrocycle formation, and 5-thiooxazole formation. Briefly discussed are two other reactions that do not take place on Cys residues.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"80 ","pages":"Article 102467"},"PeriodicalIF":7.8,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1367593124000437/pdfft?md5=ff0d2067bb16ebe523993dbaeab8b350&pid=1-s2.0-S1367593124000437-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141072924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"New analytical methods focusing on polar metabolite analysis in mass spectrometry and NMR-based metabolomics","authors":"James McCullagh, Fay Probert","doi":"10.1016/j.cbpa.2024.102466","DOIUrl":"https://doi.org/10.1016/j.cbpa.2024.102466","url":null,"abstract":"<div><p>Following in the footsteps of genomics and proteomics, metabolomics has revolutionised the way we investigate and understand biological systems. Rapid development in the last 25 years has been driven largely by technical innovations in mass spectrometry and nuclear magnetic resonance spectroscopy. However, despite the modest size of metabolomes relative to proteomes and genomes, methodological capabilities for robust, comprehensive metabolite analysis remain a major challenge. Therefore, development of new methods and techniques remains vital for progress in the field. Here, we review developments in LC-MS, GC–MS and NMR methods in the last few years that have enhanced quantitative and comprehensive metabolome coverage, highlighting the techniques involved, their technical capabilities, relative performance, and potential impact.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"80 ","pages":"Article 102466"},"PeriodicalIF":7.8,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1367593124000425/pdfft?md5=25040f8c102ce990a0b903886e423e0e&pid=1-s2.0-S1367593124000425-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141072925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Penicillin-binding protein-type thioesterases: An emerging family of non-ribosomal peptide cyclases with biocatalytic potentials","authors":"Kenichi Matsuda, Toshiyuki Wakimoto","doi":"10.1016/j.cbpa.2024.102465","DOIUrl":"https://doi.org/10.1016/j.cbpa.2024.102465","url":null,"abstract":"<div><p>Macrocyclization of peptides reduces conformational flexibilities, potentially leading to improved drug-like properties, such as target specificities and metabolic stabilities. As chemical methodologies often allow side reactions like epimerization and oligomerization, keen attention has been directed toward enzymatic peptide cyclization using peptide cyclases from specialized metabolic pathways. Penicillin-binding protein-type thioesterases (PBP-type TEs) are a recently identified family of peptide cyclases involved in the biosynthesis of non-ribosomal peptides in actinobacteria. PBP-type TEs have undergone intensive investigation due to their outstanding potential as biocatalysts. This review summarizes the rapidly growing knowledge on PBP-type TEs, with special emphasis on their functions, scopes, and structures, and efforts towards their biocatalytic applications.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"80 ","pages":"Article 102465"},"PeriodicalIF":7.8,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1367593124000413/pdfft?md5=fde71fc72bbc60c147987a83d6920144&pid=1-s2.0-S1367593124000413-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140951749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Oxygen-transfer reactions by enzymatic flavin-N5 oxygen adducts—Oxidation is not a must","authors":"Robin Teufel","doi":"10.1016/j.cbpa.2024.102464","DOIUrl":"https://doi.org/10.1016/j.cbpa.2024.102464","url":null,"abstract":"<div><p>Flavoenzymes catalyze numerous redox reactions including the transfer of an O<sub>2</sub>-derived oxygen atom to organic substrates, while the other one is reduced to water. Investigation of some of these monooxygenases led to a detailed understanding of their catalytic cycle, which involves the flavin-C<sub>4α</sub>-(hydro)peroxide as hallmark oxygenating species, and newly discovered flavoprotein monooxygenases were generally assumed to operate similarly. However, discoveries in recent years revealed a broader mechanistic versatility, including enzymes that utilize flavin-N<sub>5</sub> oxygen adducts for catalysis in the form of the flavin-N<sub>5</sub>-(hydro)peroxide and the flavin-N<sub>5</sub>-oxide species. In this review, I will highlight recent developments in that area, including noncanonical flavoenzymes from natural product biosynthesis and sulfur metabolism that provide first insights into the chemical properties of these species. Remarkably, some enzymes may even combine the flavin-N<sub>5</sub>-peroxide and the flavin-N<sub>5</sub>-oxide species for consecutive oxygen-transfers to the same substrate and thereby in essence operate as dioxygenases.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"80 ","pages":"Article 102464"},"PeriodicalIF":7.8,"publicationDate":"2024-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1367593124000401/pdfft?md5=8da170b60e8a1b645e526e1bec5a4df5&pid=1-s2.0-S1367593124000401-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140913872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Novel types of RiPP-modifying enzymes","authors":"Daniel Richter, Jörn Piel","doi":"10.1016/j.cbpa.2024.102463","DOIUrl":"https://doi.org/10.1016/j.cbpa.2024.102463","url":null,"abstract":"<div><p>Novel discoveries in natural product biosynthesis reveal hidden bioactive compounds and expand our knowledge in enzymology. Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a rapidly growing class of natural products featuring diverse non-canonical amino acids introduced by maturation enzymes as a class-defining characteristic. Underexplored RiPP sources, such as the human microbiome, the oceans, uncultured microorganisms, and plants are rich hunting grounds for novel enzymology. Unusual α- and β-amino acids, peptide cleavages, lipidations, diverse macrocyclizations, and other features expand the range of chemical groups that are installed in RiPPs by often promiscuous enzymes. This review highlights the search for novelty in RiPP enzymology in the past two years, with respect to the discovery of new biochemical modifications but also towards novel applications.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"80 ","pages":"Article 102463"},"PeriodicalIF":7.8,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1367593124000395/pdfft?md5=7cda049b2f007dbdc70542ed0bb0736b&pid=1-s2.0-S1367593124000395-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140902336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Peroxynitrite: a multifaceted oxidizing and nitrating metabolite","authors":"Carolina Prolo , Lucía Piacenza , Rafael Radi","doi":"10.1016/j.cbpa.2024.102459","DOIUrl":"https://doi.org/10.1016/j.cbpa.2024.102459","url":null,"abstract":"<div><p>Peroxynitrite, a short-lived and reactive oxidant, emerges from the diffusion-controlled reaction between the superoxide radical and nitric oxide. Evidence shows that peroxynitrite is a critical mediator in physiological and pathological processes such as the immune response, inflammation, cancer, neurodegeneration, vascular dysfunction, and aging. The biochemistry of peroxynitrite is multifaceted, involving one- or two-electron oxidations and nitration reactions. This minireview highlights recent findings of peroxynitrite acting as a metabolic mediator in processes ranging from oxidative killing to redox signaling. Selected examples of nitrated proteins (<em>i.e.,</em> 3-nitrotyrosine) are surveyed to underscore the role of this post-translational modification on cell homeostasis. While accumulated evidence shows that large amounts of peroxynitrite participates of broad oxidation and nitration events in invading pathogens and host tissues, a closer look supports that low to moderate levels selectively trigger signal transduction cascades. Peroxynitrite probes and redox-based pharmacology are instrumental to further understand the biological actions of this reactive metabolite.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"80 ","pages":"Article 102459"},"PeriodicalIF":7.8,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140878764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jonathan L. Babulic , Fabiola V. De León González , Chantelle J. Capicciotti
{"title":"Recent advances in photoaffinity labeling strategies to capture Glycan–Protein interactions","authors":"Jonathan L. Babulic , Fabiola V. De León González , Chantelle J. Capicciotti","doi":"10.1016/j.cbpa.2024.102456","DOIUrl":"https://doi.org/10.1016/j.cbpa.2024.102456","url":null,"abstract":"<div><p>Glycans decorate all cells and are critical mediators of cellular processes through recognition by glycan-binding proteins (GBPs). While targeting glycan–protein interactions has great therapeutic potential, these interactions are challenging to study as they are generally transient and exhibit low binding affinities. Glycan-based photo-crosslinkable probes have enabled covalent capture and identification of unknown GBP receptors and glycoconjugate ligands. Here, we review recent progress in photo-crosslinking approaches targeting glycan-mediated interactions. We discuss two prominent emerging strategies: 1) development of photo-crosslinkable oligosaccharide ligands to identify GBP receptors; and 2) cell-surface glyco-engineering to identify glycoconjugate ligands of GBPs. Overall, photoaffinity labeling affords valuable insights into complex glycan–protein networks and is poised to help elucidate the glycan–protein interactome, providing novel targets for therapeutic intervention.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"80 ","pages":"Article 102456"},"PeriodicalIF":7.8,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1367593124000322/pdfft?md5=bb20cf6e1a2e1e0523b2c9cc767b10c4&pid=1-s2.0-S1367593124000322-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140825487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Functions and mechanisms of enzymes assembling lignans and norlignans","authors":"Richiro Ushimaru","doi":"10.1016/j.cbpa.2024.102462","DOIUrl":"https://doi.org/10.1016/j.cbpa.2024.102462","url":null,"abstract":"<div><p>Lignans and norlignans are distributed throughout the plant kingdom and exhibit diverse chemical structures and biological properties that offer potential for therapeutic use. Originating from the phenylpropanoid biosynthesis pathway, their characteristic carbon architectures are formed through unique enzyme catalysis, featuring regio- and stereoselective C–C bond forming processes. Despite extensive research on these plant natural products, their biosynthetic pathways, and enzyme mechanisms remain enigmatic. This review highlights recent advancements in elucidating the functions and mechanisms of the biosynthetic enzymes responsible for constructing the distinct carbon frameworks of lignans and norlignans.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"80 ","pages":"Article 102462"},"PeriodicalIF":7.8,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1367593124000383/pdfft?md5=aa281046a7cc70ebdbc5b66edd629f77&pid=1-s2.0-S1367593124000383-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140813415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Towards chemoenzymatic labeling strategies for profiling protein glycosylation","authors":"Yinping Tian , Shengzhou Ma , Liuqing Wen","doi":"10.1016/j.cbpa.2024.102460","DOIUrl":"https://doi.org/10.1016/j.cbpa.2024.102460","url":null,"abstract":"<div><p>Protein glycosylation is one of the most common and important post-translational modifications of proteins involved in regulating glycoprotein functions. The chemoenzymatic glycan labeling strategy allows rapid, efficient, and selective interrogation of glycoproteins. Glycoproteomics identifies protein glycosylation events at a large scale, providing information such as peptide sequences, glycan structures, and glycosylated sites. This review discusses the recent development of chemoenzymatic labeling strategies for glycoprotein analysis, mainly including glycoprotein and glycosite profiling. Furthermore, we highlight the chemoenzymatic enrichment approaches in mass spectrometry analysis for three classes of glycan modifications, including <em>N</em>-glycosylation, <em>O</em>-GlcNAcylation, and mucin-type <em>O</em>-glycosylation. Finally, we highlight the emerging trends in new tools and cutting-edge technologies available for glycoproteomic research.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"80 ","pages":"Article 102460"},"PeriodicalIF":7.8,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140806919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fabio de Moliner , Ferran Nadal-Bufi , Marc Vendrell
{"title":"Recent advances in minimal fluorescent probes for optical imaging","authors":"Fabio de Moliner , Ferran Nadal-Bufi , Marc Vendrell","doi":"10.1016/j.cbpa.2024.102458","DOIUrl":"https://doi.org/10.1016/j.cbpa.2024.102458","url":null,"abstract":"<div><p>Fluorescent probes have revolutionized biological imaging by enabling the real-time visualization of cellular processes under physiological conditions. However, their size and potential perturbative nature can pose challenges in retaining the integrity of biological functions. This manuscript highlights recent advancements in the development of small fluorescent probes for optical imaging studies. Single benzene-based fluorophores offer versatility with minimal disruption, exhibiting diverse properties like aggregation-induced emission and pH responsiveness. Fluorescent nucleobases enable precise labeling of nucleic acids without compromising function, offering high sensitivity and compatibility with biochemistry studies. Bright yet small fluorescent amino acids provide an interesting alternative to bulky fusion proteins, facilitating non-invasive imaging of cellular events with high precision. These miniaturized fluorophores promise enhanced capabilities for studying biological systems in a non-invasive manner, fostering further innovations in molecular imaging.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"80 ","pages":"Article 102458"},"PeriodicalIF":7.8,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1367593124000346/pdfft?md5=ba2c27d3c9b85e9d0076f896b3a16938&pid=1-s2.0-S1367593124000346-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140644291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}