Microbial Biotechnology最新文献

{"title":"Extending the Targets for Coronavirus Antivirals Beyond That of Approved Drugs: Insights From Preclinical Research","authors":"Harald Brüssow","doi":"10.1111/1751-7915.70376","DOIUrl":"10.1111/1751-7915.70376","url":null,"abstract":"<p>Antiviral drugs have been approved for the treatment of COVID-19. However, they present pharmacological limitations, a mixed efficacy profile and target just two coronavirus proteins. To extend the range of druggable coronavirus proteins, researchers explored small molecule N-glycan binders as inhibitors of SARS-CoV-2 spike protein interaction with the cell receptor. Other groups investigated lipopeptides as inhibitors of cell fusion by viral spikes. High throughput screening of chemical libraries yielded viral maturation inhibitors that targeted the viral M protein. Massive screening led to inhibitors of the non-structural coronavirus protein NSP14, a methyltransferase involved in viral mRNA cap synthesis. Machine learning–driven scans of chemical space revealed inhibitors of non-structural coronavirus protein NSP3, a papain-like protease subverting innate immune response to viral infection. A chimera of a nucleotide analogue coupled to an RNase L attractor bound the RNA-dependent RNA polymerase NSP12 and mediated degradation of the viral RNA. Several of these compounds showed comparable or even superior antiviral efficacy as approved COVID-19 drugs in preclinical animal tests. Parallel efforts were made to develop chemical compounds targeting host proteins needed for viral multiplication. Peptidomimetic tetrapeptides acted as inhibitors of the host protease TMPRSS2 involved in cell fusion by the viral spike protein. A repurposed TMPRSS2 inhibitor was tested in COVID-19 patients without demonstrating efficacy. A genetic screen demonstrated an enzyme involved in sphingomyelin synthesis and its inhibitor which impaired SARS-CoV-2 replication. A viral-cell protein interactome study showed 332 cellular proteins interacting with 26 coronaviral proteins. A chemoinformatic search found inhibitors for the interaction of NSP9 with host elongation factor eIF4A and for NSP13 with elongation factor eEF1A. Plitidepsin, a clinically used eEF1A inhibitor, was tested in human clinical trials with COVID-19 patients demonstrating in vivo antiviral activity and a trend for clinical amelioration in an underpowered phase 3 clinical trial.</p>","PeriodicalId":209,"journal":{"name":"Microbial Biotechnology","volume":"19 5","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1751-7915.70376","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147985430","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":209,"journal":{"name":"Microbial Biotechnology","volume":"19 5","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148087934","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}

{"title":"A Stereospecific Lactic Acid Exclusion Biosensor for Grass Silage Fed Green Biorefinery","authors":"Roderick N. van Roosmalen,&nbsp;Cormac D. Murphy,&nbsp;Joseph B. Sweeney","doi":"10.1111/1751-7915.70374","DOIUrl":"10.1111/1751-7915.70374","url":null,"abstract":"<p>Grass silage fed green biorefineries require high quality grass silage leachates to produce high quality products. Real-time, cost-effective methods to monitor key leachate analytes are needed for small-scale decentralised systems. In this study, <i>Escherichia coli</i> mutants, designated JSP0090 and JSP0094, were created to quantify <span>d</span>- and <span>l</span>-lactic acid concentrations in grass leachate samples using an oxygen probe. The genes encoding either <span>d</span>- or <span>l</span>-lactate dehydrogenase were expressed in an exclusion biosensor strain (JSK0115). This strain required successive gene deletions to prevent interference from sugars, amino acids and organic acids present in grass silage leachates. This strain was incapable of catabolising <span>d</span>-lactic acid, <span>l</span>-lactic acid, acetic acid, propionic acid, formic acid, ethanol, glucose, fructose, <span>l</span>-alanine, VFAs, glycerol, mannitol and succinate. Gene knockouts were achieved using P1 phage lysates and CRISPR Cas 9 methods to target key steps in the catabolism of these compounds, with the exception of succinate. For this metabolite, the di-carboxylic acid transporters YaaH, DctA, YchM, DcuA and DcuB had to be deleted. The effectiveness of the biosensors for selectively measuring <span>d-</span> and <span>l</span>-lactic acid was assessed in Austrian and Irish grass silage leachate. The concentrations measured were comparable to those obtained using a commercial enzyme kit.</p>","PeriodicalId":209,"journal":{"name":"Microbial Biotechnology","volume":"19 5","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1751-7915.70374","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147985411","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":209,"journal":{"name":"Microbial Biotechnology","volume":"19 5","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148085377","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}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":209,"journal":{"name":"Microbial Biotechnology","volume":"19 5","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148086741","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}

{"title":"Correction to ‘Identification and Characterisation of the Gene Cluster Governing Biosynthesis of the Anti-Mycobacterial Antibiotic Acidomycin’","authors":"","doi":"10.1111/1751-7915.70377","DOIUrl":"10.1111/1751-7915.70377","url":null,"abstract":"<p>Vignolle, A., M. Zehl, J. F. G. Garzón, et al. 2026. ‘Identification and Characterisation of the Gene Cluster Governing Biosynthesis of the Anti-Mycobacterial Antibiotic Acidomycin.’ <i>Microbial Biotechnology</i> 19, no. 4: e70357. https://doi.org/10.1111/1751-7915.70357.</p><p>In the originally published version of this article, the Author Contributions section is incomplete. The correct Author Contributions section should be as follows:</p><p><b>Anna Vignolle:</b> investigation, writing – original draft. <b>Martin Zehl:</b> investigation, methodology, validation, writing – original draft, writing – review and editing. <b>Jaime Felipe Guerrero Garzón:</b> investigation, methodology, validation, writing – original draft; <b>Olha Schneider:</b> investigation, methodology, writing – original draft. <b>Johannes Gafriller:</b> investigation, methodology. <b>Ulrike Grienke:</b> investigation, writing – original draft, validation, methodology. <b>Rasmus H. Kirkegaard:</b> investigation, methodology. <b>Sergey B. Zotchev:</b> conceptualization, investigation, funding acquisition, writing – original draft, writing – review and editing, project administration, supervision.</p><p>The online version of this article has been corrected accordingly.</p>","PeriodicalId":209,"journal":{"name":"Microbial Biotechnology","volume":"19 5","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1751-7915.70377","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147979725","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":209,"journal":{"name":"Microbial Biotechnology","volume":"19 5","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148083289","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}

{"title":"Incorporation of Cryptic Plasmid Energetics Improves Genome-Scale Metabolic Predictions in Probiotic E. coli Nissle 1917","authors":"Paola Corbín-Agustí,&nbsp;Alba Arévalo-Lalanne,&nbsp;Patricia Álvarez,&nbsp;Maria Enrique,&nbsp;Daniel Ramón,&nbsp;Juli Peretó,&nbsp;Marta Tortajada","doi":"10.1111/1751-7915.70361","DOIUrl":"10.1111/1751-7915.70361","url":null,"abstract":"<p><i>Escherichia coli</i> Nissle 1917 (EcN) is a well-characterized Gram-negative probiotic distinguished by its unique, strain-specific physiology. Genome-scale metabolic models (GEMs) are powerful tools for elucidating metabolic traits and predicting genotype-phenotype relationships. Although several EcN GEMs have been published, none have explicitly exploited its probiotic physiology. Here, we present a plasmid-specific module that can be incorporated into EcN GEMs, which, for the first time, considers the energetic costs associated with its cryptic plasmids. Using COBRA methodologies and possibilistic metabolic flux analysis, we show how the plasmid-module inclusion improves biomass and overall flux predictions in an additional, manually curated EcN model as well as in previous EcN reconstructions. Then, the different EcN reconstructions were systematically compared to evaluate the trade-off between model refinement depth and predictive performance. The analysis revealed that once expanded to include the plasmid-related costs, increased level of curation in the different GEMs does not necessarily enhance quantitative accuracy and that predictive reliability depends on both computational methodology chosen and experimental contexts. Metabolomic profiling under gut microbiota medium and anaerobic conditions further showed that EcN exhibits a distinctive metabolic phenotype, characterized by elevated amino acid consumption and enhanced short-chain fatty acid production, which is captured by the evaluated metabolic models. These findings highlight the unique probiotic physiology of EcN and demonstrate the utility of metabolic modelling for reproducing and exploring such traits. Overall, this study provides a quantitatively reliable and physiologically relevant framework for modelling <i>E. coli</i> Nissle 1917 while considering its cryptic plasmids, supporting advances in probiotic engineering, synthetic biology and bioprocess design.</p>","PeriodicalId":209,"journal":{"name":"Microbial Biotechnology","volume":"19 5","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13184178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147968945","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":"Engineering Chondroitinase-Free Baculovirus-Insect Cell Expression System for Efficient Synthesis of Chondroitin Sulphates","authors":"Junyue Li,&nbsp;Yuqing Tian,&nbsp;Lihe She,&nbsp;Zhangliang Liu,&nbsp;Yingying Zhou,&nbsp;Yanyan Wang,&nbsp;Jihui Zhang,&nbsp;Leilei Zhu,&nbsp;Huarong Tan,&nbsp;Jine Li","doi":"10.1111/1751-7915.70365","DOIUrl":"10.1111/1751-7915.70365","url":null,"abstract":"<p>Owing to the high expression levels, proper protein folding and post-translational modifications, baculovirus-insect cell expression system is an ideal platform for producing active chondroitin sulfotransferases, which specifically catalyse the synthesis of chondroitin sulphate (CS). However, the CS can be degraded by the endogenous chondroitinase derived from the viral envelope protein ODV-E66, thus requiring elaborate purification, which is impractical for large-scale production. To address this issue, a chondroitinase-free baculovirus was constructed by deleting the <i>odv-e66</i> gene from bacterial artificial chromosomes (BACs). Through the engineered baculovirus, highly active chondroitin sulfotransferases (CS-4OST, CS-6OST and GalNAc4S-6OST) were successfully expressed and secreted into the culture supernatant. Of note, the culture supernatant can be directly employed for CS synthesis. Using the cultures harbouring the corresponding sulfotransferases, CS-A, CS-C and CS-E were successfully prepared at the gram-scale, thus obviating the need for laborious and costly purification. Collectively, this work overcomes the inherent limitation of CS degradation in baculovirus-insect cell expression system, thereby providing a robust and reliable platform for the expression of chondroitin sulfotransferases.</p>","PeriodicalId":209,"journal":{"name":"Microbial Biotechnology","volume":"19 5","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13176938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147939353","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":209,"journal":{"name":"Microbial Biotechnology","volume":"19 5","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148079728","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}