Essays in biochemistry最新文献

{"title":"Considerations for prioritising clinical research using bacteriophage.","authors":"Sarah J L Edwards, Yiran Tao, Rodas Elias, Robert Schooley","doi":"10.1042/EBC20240013","DOIUrl":"10.1042/EBC20240013","url":null,"abstract":"<p><p>Antimicrobial resistance (AMR) poses a significant global health threat, as it contributes to prolonged illness, higher mortality rates and increased healthcare costs. As traditional antibiotics become less effective, treatments such as bacteriophage therapy offer potential solutions. The question remains, however, on how to set research priorities in the face of a growing number of antibiotic-resistant pathogens, some common and/or dangerous. One standard way of making decisions about which research to prioritise is by using the disability-adjusted life year metric to estimate the current global impact of a disease or condition, combined with considerations of social justice although decisions made at a national level by governments, especially in low income countries with forecasting potential over future needs may look very different. Another approach is based on the needs of researchers and regulators given what we know about the technology itself. The biological characteristics of bacteriophage therapies set challenges to a universal and standardised prioritisation method. A proof of principle is still arguably needed. With a preliminary discussion of the scope and complexity of AMR and AMR therapeutics, we propose some implications of regulatory frameworks aiming to integrate bacteriophage therapy into mainstream medical practice while gathering scientific data on safety and efficacy, enhancing the collective action needed to combat AMR.</p>","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":" ","pages":"679-686"},"PeriodicalIF":5.6,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544460","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":"The new age of the phage.","authors":"Joanne M Santini","doi":"10.1042/EBC20240037","DOIUrl":"10.1042/EBC20240037","url":null,"abstract":"<p><p>The discovery of viruses that can devour bacteria, bacteriophages (phages), was in 1915. Phages are ubiquitous, outnumbering the organisms they devour, and genomically, morphologically, and ecologically diverse. They were critical in our development of molecular biology and biotechnology tools and have been used as therapeutics for over 100 years, primarily in Eastern Europe with thousands of patients from all over the world treated in Georgia. The rise of antimicrobial resistance and the lack of new antimicrobials, has brought them back into the spotlight dawning the New Age of the Phage. This special issue will provide further insight to phage diversity across ecosystems, including humans, animals, and plants, i.e. the basis of a One Health approach, and the requirements for turning phages into viable medicines for the many and not just for the few.</p>","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":"68 5","pages":"579-581"},"PeriodicalIF":5.6,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834750","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":"A comparative guide to expression systems for phage lysin production.","authors":"Emma Cremelie, Roberto Vázquez, Yves Briers","doi":"10.1042/EBC20240019","DOIUrl":"10.1042/EBC20240019","url":null,"abstract":"<p><p>Phage lysins, bacteriophage-encoded enzymes tasked with degrading their host's cell wall, are increasingly investigated and engineered as novel antibacterials across diverse applications. Their rapid action, tuneable specificity, and low likelihood of resistance development make them particularly interesting. Despite numerous application-focused lysin studies, the art of their recombinant production remains relatively undiscussed. Here, we provide an overview of the available expression systems for phage lysin production and discuss key considerations guiding the choice of a suitable recombinant host. We systematically surveyed recent literature to evaluate the hosts used in the lysin field and cover various recombinant systems, including the well-known bacterial host Escherichia coli or yeast Saccharomyces cerevisiae, as well as plant, mammalian, and cell-free systems. Careful analysis of the limited studies expressing lysins in various hosts suggests a host-dependent effect on activity. Nonetheless, the multitude of available expression systems should be further leveraged to accommodate the growing interest in phage lysins and their expanding range of applications.</p>","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":" ","pages":"645-659"},"PeriodicalIF":5.6,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282305","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":"Sulfation pathways in times of change.","authors":"Jonathan Wolf Mueller, Daniela Fietz, Irundika H K Dias","doi":"10.1042/EBC20230099","DOIUrl":"10.1042/EBC20230099","url":null,"abstract":"<p><p>Sulfation pathways are an essential part of overall sulfur metabolism. Sulfation pathways are mainly about sulfate activation, and the making and breaking of biological sulfate esters. This special issue features some extended reflection on what was presented at the SUPA 2023 meeting on Sulfation Pathways. Novel insights into the synthesis and analytics of sulfate, of sulfated conjugates, and of protein persulfides are presented. Oxysterol sulfates are presented as emerging sulfo-metabolites. Sulfation pathways enzymes are discussed in various disease settings. This special issue also presents insights into polysaccharide sulfotransferases and their functional characterization. Finally, cytoplasmic sulfotransferases are highlighted with regards to their impact on DNA-modification, and in the context of endocrine disruptors. All in all, thought-provoking findings, with the potential to guide and stimulate future research in the field of sulfation pathways and beyond.</p>","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":"68 4","pages":"379-382"},"PeriodicalIF":5.6,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11625859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767445","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":"Oxysterol sulfates in fluids, cells and tissues: how much do we know about their clinical significance, biological relevance and biophysical implications?","authors":"Ana Reis, Irundika H K Dias","doi":"10.1042/EBC20230090","DOIUrl":"10.1042/EBC20230090","url":null,"abstract":"<p><p>Oxysterol sulfates are emerging as key players in lipid homeostasis, inflammation and immunity. Despite this, knowledge on their basal levels in fluids, cells and tissues and any changes associated with age, gender and diet in health and disease; as well as their spatio-temporal distribution in cell membranes and organelles have been greatly hampered by the lack of commercially available pure synthetic standards. Expansion of the panel of pure oxysterol sulfates standards is pivotal to improve our understanding on the impact of oxysterol sulfates at the membrane level and their role in cellular events. While the clinical significance, biophysical implications and biological relevance of oxysterol sulfates in fluids, cells and tissues remains largely unknown, knowledge already gathered on the precursors of oxysterol sulfates (e.g. oxysterols and cholesterol sulfate) can be used to guide researchers on the most relevant aspects to search for when screening for oxysterol sulfates bioavailability in (patho)physiological conditions which are crucial in the design of biophysical and of cell-based assays. Herein, we provide a review on the brief knowledge involving oxysterol sulfate and an overview on the biophysical implications and biological relevance of oxysterols and cholesterol sulfate useful to redirect further investigations on the role of oxysterol sulfates in health and disease.</p>","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":" ","pages":"401-410"},"PeriodicalIF":5.6,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11625865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140305299","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":"Sulphotransferase-mediated toxification of chemicals in mouse models: effect of knockout or humanisation of SULT genes.","authors":"Hansruedi Glatt, Walter Meinl","doi":"10.1042/EBC20240030","DOIUrl":"10.1042/EBC20240030","url":null,"abstract":"<p><p>Cytosolic sulphotransferase (SULT) enzymes catalyse reactions involved in xenobiotic elimination and hormone regulation. However, SULTs can also generate electrophilic reactive intermediates from certain substrates, including the activation of carcinogens. Here, we review toxicological studies of mouse strains with SULT status altered by genetic modification. Knockout mouse strains have been constructed for the enzymes Sult1a1, 1d1, 1e1, 2b1 and 4a1. In addition, transgenic strains are available for human SULT1A1/2. Among SULT knockout mouse strains, reduced fertility (Sult1e1) and early postnatal death (Sult4a1) were observed. In contrast, Sult1a1 or Sult1d1 knockouts and SULT1A1/2 transgenics were healthy and showed no obvious deficiencies. These strains were used in toxicological studies with 13 chemicals. Manipulation of the SULT system altered dramatically the adverse effects of many compounds; thus, very large differences in levels of DNA adducts formed in the liver or other tissues were seen with some chemicals - up to 99.2% decreases in knockouts and 83-fold increases in SULT1A1/2 transgenics. In many cases, these changes were restricted to the tissues in which the corresponding enzymes are expressed, arguing for local activation. However, with some compounds, the kidney was an important target tissue, due to the active transfer to that organ, via the circulation, of reactive sulphuric acid esters.</p>","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":" ","pages":"523-539"},"PeriodicalIF":5.6,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11625864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750266","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":"Quantification of persulfidation on specific proteins: are we nearly there yet?","authors":"Hongling Liu, Florentina Negoita, Matthew Brook, Kei Sakamoto, Nicholas M Morton","doi":"10.1042/EBC20230095","DOIUrl":"10.1042/EBC20230095","url":null,"abstract":"<p><p>Hydrogen sulfide (H2S) played a pivotal role in the early evolution of life on Earth before the predominance of atmospheric oxygen. The legacy of a persistent role for H2S in life's processes recently emerged through its discovery in modern biochemistry as an endogenous cellular signalling modulator involved in numerous biological processes. One major mechanism through which H2S signals is protein cysteine persulfidation, an oxidative post-translational modification. In recent years, chemoproteomic technologies have been developed to allow the global scanning of protein persulfidation targets in mammalian cells and tissues, providing a powerful tool to elucidate the broader impact of altered H2S in organismal physiological health and human disease states. While hundreds of proteins were confirmed to be persulfidated by global persulfidome methodologies, the targeting of specific proteins of interest and the investigation of further mechanistic studies are still underdeveloped due to a lack of stringent specificity of the methods and the inherent instability of persulfides. This review provides an overview of the processes of endogenous H2S production, oxidation, and signalling and highlights the application and limitations of current persulfidation labelling approaches for investigation of this important evolutionarily conserved biological switch for protein function.</p>","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":" ","pages":"467-478"},"PeriodicalIF":5.6,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11625863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282308","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":"Chemical approaches to the sulfation of small molecules: current progress and future directions.","authors":"Jaber A Alshehri, Alan M Jones","doi":"10.1042/EBC20240001","DOIUrl":"10.1042/EBC20240001","url":null,"abstract":"<p><p>Sulfation is one of the most important modifications that occur to a wide range of bioactive small molecules including polysaccharides, proteins, flavonoids, and steroids. In turn, these sulfated molecules have significant biological and pharmacological roles in diverse processes including cell signalling, modulation of immune and inflammation response, anti-coagulation, anti-atherosclerosis, and anti-adhesive properties. This Essay summarises the most encountered chemical sulfation methods of small molecules. Sulfation reactions using sulfur trioxide amine/amide complexes are the most used method for alcohol and phenol groups in carbohydrates, steroids, proteins, and related scaffolds. Despite the effectiveness of these methods, they suffer from issues including multiple-purification steps, toxicity issues (e.g., pyridine contamination), purification challenges, stoichiometric excess of reagents which leads to an increase in reaction cost, and intrinsic stability issues of both the reagent and product. Recent advances including SuFEx, the in situ reagent approach, and TBSAB show the widespread appeal of novel sulfating approaches that will enable a larger exploration of the field in the years to come by simplifying the purification and isolation process to access bespoke sulfated small molecules.</p>","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":" ","pages":"449-466"},"PeriodicalIF":5.6,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11625868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491365","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":"Cytosolic sulfotransferases in endocrine disruption.","authors":"Michael W Duffel","doi":"10.1042/EBC20230101","DOIUrl":"10.1042/EBC20230101","url":null,"abstract":"<p><p>The mammalian cytosolic sulfotransferases (SULTs) catalyze the sulfation of endocrine hormones as well as a broad array of drugs, environmental chemicals, and other xenobiotics. Many endocrine-disrupting chemicals (EDCs) interact with these SULTs as substrates and inhibitors, and thereby alter sulfation reactions responsible for metabolism and regulation of endocrine hormones such as estrogens and thyroid hormones. EDCs or their metabolites may also regulate expression of SULTs through direct interaction with nuclear receptors and other transcription factors. Moreover, some sulfate esters derived from EDCs (EDC-sulfates) may serve as ligands for endocrine hormone receptors. While the sulfation of an EDC can lead to its excretion in the urine or bile, it may also result in retention of the EDC-sulfate through its reversible binding to serum proteins and thereby enable transport to other tissues for intracellular hydrolysis and subsequent endocrine disruption. This mini-review outlines the potential roles of SULTs and sulfation in the effects of EDCs and our evolving understanding of these processes.</p>","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":" ","pages":"541-553"},"PeriodicalIF":5.6,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140849161","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":"Genetic variability in proteoglycan biosynthetic genes reveals new facets of heparan sulfate diversity.","authors":"Mohand Ouidir Ouidja, Denis S F Biard, Minh Bao Huynh, Xavier Laffray, Wilton Gomez-Henao, Sandrine Chantepie, Gael Le Douaron, Nicolas Rebergue, Auriane Maïza, Heloise Merrick, Aubert De Lichy, Alwyn Dady, Oscar González-Velasco, Karla Rubio, Guillermo Barreto, Kévin Baranger, Valerie Cormier-Daire, Javier De Las Rivas, David G Fernig, Dulce Papy-Garcia","doi":"10.1042/EBC20240106","DOIUrl":"10.1042/EBC20240106","url":null,"abstract":"<p><p>Heparan sulfate (HS) and chondroitin sulfate (CS) proteoglycans (PG) consist of a core protein to which the glycosaminoglycan (GAG) chains, HS or CS, are attached through a common linker tetrasaccharide. In the extracellular space, they are involved in the regulation of cell communication, assuring development and homeostasis. The HSPG biosynthetic pathway has documented 51 genes, with many diseases associated to defects in some of them. The phenotypic consequences of this genetic variation in humans, and of genetic ablation in mice, and their expression patterns, led to a phenotypically centered HSPG biosynthetic pathway model. In this model, HS sequences produced by ubiquitous NDST1, HS2ST and HS6ST enzymes are essential for normal development and homeostasis, whereas tissue restricted HS sequences produced by the non-ubiquitous NDST2-4, HS6ST2-3, and HS3ST1-6 enzymes are involved in adaptative behaviors, cognition, tissue responsiveness to stimuli, and vulnerability to disease. The model indicates that the flux through the HSPG/CSPG pathways and its diverse branches is regulated by substrate preferences and protein-protein-interactions. This results in a privileged biosynthesis of HSPG over that of CSPGs, explaining the phenotypes of linkeropathies, disease caused by defects in genes involved in the biosynthesis of the common tetrasaccharide linker. Documented feedback loops whereby cells regulate HS sulfation, and hence the interactions of HS with protein partners, may be similarly implemented, e.g., protein tyrosine sulfation and other posttranslational modifications in enzymes of the HSPG pathway. Together, ubiquitous HS, specialized HS, and their biosynthesis model can facilitate research for a better understanding of HSPG roles in physiology and pathology.</p>","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":"68 4","pages":"555-578"},"PeriodicalIF":5.6,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11625870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767438","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}