{"title":"HPClas: A data‐driven approach for identifying halophilic proteins based on catBoost","authors":"Shantong Hu, Xiao-Yong Wang, Zhikang Wang, Menghan Jiang, Shihui Wang, Wenya Wang, Jiangning Song, Guimin Zhang","doi":"10.1002/mlf2.12125","DOIUrl":"https://doi.org/10.1002/mlf2.12125","url":null,"abstract":"Halophilic proteins possess unique structural properties and show high stability under extreme conditions. This distinct characteristic makes them invaluable for application in various aspects such as bioenergy, pharmaceuticals, environmental clean‐up, and energy production. Generally, halophilic proteins are discovered and characterized through labor‐intensive and time‐consuming wet lab experiments. In this study, we introduce the Halophilic Protein Classifier (HPClas), a machine learning‐based classifier developed using the catBoost ensemble learning technique to identify halophilic proteins. Extensive in silico calculations were conducted on a large public dataset of 12,574 samples and HPClas achieved an area under the receiver operating characteristic curve (AUROC) of 0.844 on an independent test set of 200 samples. The source code and curated dataset of HPClas are publicly available at https://github.com/Showmake2/HPClas. In conclusion, HPClas can be explored as a promising tool to aid in the identification of halophilic proteins and accelerate their application in different fields.","PeriodicalId":94145,"journal":{"name":"mLife","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141819453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
mLifePub Date : 2024-06-28eCollection Date: 2024-06-01DOI: 10.1002/mlf2.12132
Pan Zhang, Biliang Zhang, Yuan-Yuan Ji, Jian Jiao, Ziding Zhang, Chang-Fu Tian
{"title":"Cofitness network connectivity determines a fuzzy essential zone in open bacterial pangenome.","authors":"Pan Zhang, Biliang Zhang, Yuan-Yuan Ji, Jian Jiao, Ziding Zhang, Chang-Fu Tian","doi":"10.1002/mlf2.12132","DOIUrl":"10.1002/mlf2.12132","url":null,"abstract":"<p><p>Most in silico evolutionary studies commonly assumed that core genes are essential for cellular function, while accessory genes are dispensable, particularly in nutrient-rich environments. However, this assumption is seldom tested genetically within the pangenome context. In this study, we conducted a robust pangenomic Tn-seq analysis of fitness genes in a nutrient-rich medium for <i>Sinorhizobium</i> strains with a canonical open pangenome. To evaluate the robustness of fitness category assignment, Tn-seq data for three independent mutant libraries per strain were analyzed by three methods, which indicates that the Hidden Markov Model (HMM)-based method is most robust to variations between mutant libraries and not sensitive to data size, outperforming the Bayesian and Monte Carlo simulation-based methods. Consequently, the HMM method was used to classify the fitness category. Fitness genes, categorized as essential (ES), advantage (GA), and disadvantage (GD) genes for growth, are enriched in core genes, while nonessential genes (NE) are over-represented in accessory genes. Accessory ES/GA genes showed a lower fitness effect than core ES/GA genes. Connectivity degrees in the cofitness network decrease in the order of ES, GD, and GA/NE. In addition to accessory genes, 1599 out of 3284 core genes display differential essentiality across test strains. Within the pangenome core, both shared quasi-essential (ES and GA) and strain-dependent fitness genes are enriched in similar functional categories. Our analysis demonstrates a considerable fuzzy essential zone determined by cofitness connectivity degrees in <i>Sinorhizobium</i> pangenome and highlights the power of the cofitness network in understanding the genetic basis of ever-increasing prokaryotic pangenome data.</p>","PeriodicalId":94145,"journal":{"name":"mLife","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11211677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141474093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Identification of 3-ketocapnine reductase activity within the human microbiota.","authors":"Xiaotong Wu, Lukuan Hou, Haili Zhang, Yi Ma, Jufang Wang, Mingwei Cai, Xiaoyu Tang","doi":"10.1002/mlf2.12134","DOIUrl":"10.1002/mlf2.12134","url":null,"abstract":"<p><p>The microbial synthesis of sulfonolipids within the human body is likely involved in maintaining human health or causing diseases. However, the enzymes responsible for their biosynthesis remain largely unknown. In this study, we identified and verified the role of 3-ketocapnine reductase, the third-step enzyme, in the four-step conversion of l-phosphoserine into sulfobacin B both in vivo and in vitro. This finding builds upon our previous research into sulfonolipid biosynthesis, which focused on the vaginal bacterium <i>Chryseobacterium gleum</i> DSM 16776 and the gut bacterium <i>Alistipes finegoldii</i> DSM 17242. Through comprehensive gene mapping, we demonstrate the widespread presence of potential sulfonolipid biosynthetic genes across diverse bacterial species inhabiting various regions of the human body. These findings shed light on the prevalence of sulfonolipid-like metabolites within the human microbiota, suggesting a potential role for these lipid molecules in influencing the intricate biointeractions within the complex microbial ecosystem of the human body.</p>","PeriodicalId":94145,"journal":{"name":"mLife","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11211663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141474652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
mLifePub Date : 2024-06-28eCollection Date: 2024-06-01DOI: 10.1002/mlf2.12126
Ching Tse, Kesen Ma
{"title":"A novel alcohol dehydrogenase in the hyperthermophilic crenarchaeon <i>Hyperthermus butylicus</i>.","authors":"Ching Tse, Kesen Ma","doi":"10.1002/mlf2.12126","DOIUrl":"10.1002/mlf2.12126","url":null,"abstract":"<p><p><i>Hyperthermus butylicus</i> is a hyperthermophilic crenarchaeon that produces 1-butanol as an end product. A thermostable alcohol dehydrogenase (ADH) must be present in <i>H. butylicus</i> to act as the key enzyme responsible for this production; however, the gene that encodes the ADH has not yet been identified. A novel ADH, HbADH2, was purified from a cell-free extract of <i>H. butylicus</i>, and its characteristics were determined. The gene that encodes HbADH2 was demonstrated to be <i>HBUT_RS04850</i> and annotated as a hypothetical protein in <i>H. butylicus</i>. HbADH2 was found to be a primary-secondary ADH capable of using a wide range of substrates, including butyraldehyde and butanol. Butyraldehyde had the highest specificity constant, calculated as <i>k</i> <sub>c</sub> <sub>at</sub>/<i>K</i> <sub>m</sub>, with <i>k</i> <sub>cat</sub> and apparent <i>K</i> <sub>m</sub> values of 8.00 ± 0.22 s<sup>-1</sup> and 0.59 ± 0.07 mM, respectively. The apparent <i>K</i> <sub>m</sub> values for other substrates, including ethanol, 1-propanol, 2-propanol, butanol, acetaldehyde, propanal, and acetone, were 4.36 ± 0.42, 4.69 ± 0.41, 3.74 ± 0.46, 2.44 ± 0.30, 1.27 ± 0.18, 1.55 ± 0.20, and 0.68 ± 0.04 mM, respectively. The optimal pH values for catalyzing aldehyde reduction and alcohol oxidation were 6.0 and 9.0, respectively, while the optimal temperature was higher than 90°C due to the increase in enzymatic activity from 60°C to 90°C. Based on its substrate specificity, enzyme kinetics, and thermostability, HbADH2 may be the ADH that catalyzes the production of 1-butanol in <i>H. butylicus</i>. The putative conserved motif sites for NAD(P)<sup>+</sup> and iron binding were identified by aligning HbADH2 with previously characterized Fe-containing ADHs.</p>","PeriodicalId":94145,"journal":{"name":"mLife","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11211662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141474092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
mLifePub Date : 2024-06-28eCollection Date: 2024-06-01DOI: 10.1002/mlf2.12133
Di Wang, Toshiyuki Ueki, Peiyu Ma, Dake Xu, Derek R Lovley
{"title":"Elucidating microbial iron corrosion mechanisms with a hydrogenase-deficient strain of <i>Desulfovibrio vulgaris</i>.","authors":"Di Wang, Toshiyuki Ueki, Peiyu Ma, Dake Xu, Derek R Lovley","doi":"10.1002/mlf2.12133","DOIUrl":"10.1002/mlf2.12133","url":null,"abstract":"<p><p>Sulfate-reducing microorganisms extensively contribute to the corrosion of ferrous metal infrastructure. There is substantial debate over their corrosion mechanisms. We investigated Fe<sup>0</sup> corrosion with <i>Desulfovibrio vulgaris</i>, the sulfate reducer most often employed in corrosion studies. Cultures were grown with both lactate and Fe<sup>0</sup> as potential electron donors to replicate the common environmental condition in which organic substrates help fuel the growth of corrosive microbes. Fe<sup>0</sup> was corroded in cultures of a <i>D. vulgaris</i> hydrogenase-deficient mutant with the 1:1 correspondence between Fe<sup>0</sup> loss and H<sub>2</sub> accumulation expected for Fe<sup>0</sup> oxidation coupled to H<sup>+</sup> reduction to H<sub>2</sub>. This result and the extent of sulfate reduction indicated that <i>D. vulgaris</i> was not capable of direct Fe<sup>0</sup>-to-microbe electron transfer even though it was provided with a supplementary energy source in the presence of abundant ferrous sulfide. Corrosion in the hydrogenase-deficient mutant cultures was greater than in sterile controls, demonstrating that H<sub>2</sub> removal was not necessary for the enhanced corrosion observed in the presence of microbes. The parental H<sub>2</sub>-consuming strain corroded more Fe<sup>0</sup> than the mutant strain, which could be attributed to H<sub>2</sub> oxidation coupled to sulfate reduction, producing sulfide that further stimulated Fe<sup>0</sup> oxidation. The results suggest that H<sub>2</sub> consumption is not necessary for microbially enhanced corrosion, but H<sub>2</sub> oxidation can indirectly promote corrosion by increasing sulfide generation from sulfate reduction. The finding that <i>D. vulgaris</i> was incapable of direct electron uptake from Fe<sup>0</sup> reaffirms that direct metal-to-microbe electron transfer has yet to be rigorously described in sulfate-reducing microbes.</p>","PeriodicalId":94145,"journal":{"name":"mLife","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11211667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141474094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cinnamaldehyde targets SarA to enhance β‐lactam antibiotic activity against methicillin‐resistant Staphylococcus aureus","authors":"Jianguo Li, Tingyin Lu, Yue-Fei Chu, Yuejun Zhang, Jing Zhang, Wenzhen Fu, Jian Sun, Yahong Liu, Xiaoping Liao, Yu-Feng Zhou","doi":"10.1002/mlf2.12121","DOIUrl":"https://doi.org/10.1002/mlf2.12121","url":null,"abstract":"Methicillin‐resistant Staphylococcus aureus (MRSA) is a current global public health problem due to its increasing resistance to the most recent antibiotic therapies. One critical approach is to develop ways to revitalize existing antibiotics. Here, we show that the phytogenic compound cinnamaldehyde (CIN) and β‐lactam antibiotic combinations can functionally synergize and resensitize clinical MRSA isolates to β‐lactam therapy and inhibit MRSA biofilm formation. Mechanistic studies indicated that the CIN potentiation effect on β‐lactams was primarily the result of inhibition of the mecA expression by targeting the staphylococcal accessory regulator sarA. CIN alone or in combination with β‐lactams decreased sarA gene expression and increased SarA protein phosphorylation that impaired SarA binding to the mecA promoter element and downregulated virulence genes such as those encoding biofilm, α‐hemolysin, and adhesin. Perturbation of SarA–mecA binding thus interfered with PBP2a biosynthesis and this decreased MRSA resistance to β‐lactams. Furthermore, CIN fully restored the anti‐MRSA activities of β‐lactam antibiotics in vivo in murine models of bacteremia and biofilm infections. Together, our results indicated that CIN acts as a β‐lactam adjuvant and can be applied as an alternative therapy to combat multidrug‐resistant MRSA infections.","PeriodicalId":94145,"journal":{"name":"mLife","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141340550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
mLifePub Date : 2024-05-27eCollection Date: 2024-06-01DOI: 10.1002/mlf2.12123
Tao Wang, Peng Tan, Qi Tang, Chenlong Zhou, Yakun Ding, Shenrui Xu, Mengda Song, Huiyang Fu, Yucheng Zhang, Xiaohui Zhang, Yueyu Bai, Zhihong Sun, Xi Ma
{"title":"Phage-displayed heptapeptide sequence conjugation significantly improves the specific targeting ability of antimicrobial peptides against <i>Staphylococcus aureus</i>.","authors":"Tao Wang, Peng Tan, Qi Tang, Chenlong Zhou, Yakun Ding, Shenrui Xu, Mengda Song, Huiyang Fu, Yucheng Zhang, Xiaohui Zhang, Yueyu Bai, Zhihong Sun, Xi Ma","doi":"10.1002/mlf2.12123","DOIUrl":"10.1002/mlf2.12123","url":null,"abstract":"<p><p>Broad-spectrum antibacterial drugs often lack specificity, leading to indiscriminate bactericidal activity, which can disrupt the normal microbial balance of the host flora and cause unnecessary cytotoxicity during systemic administration. In this study, we constructed a specifically targeted antimicrobial peptide against <i>Staphylococcus aureus</i> by introducing a phage-displayed peptide onto a broad-spectrum antimicrobial peptide and explored its structure-function relationship through one-factor modification. SFK2 obtained by screening based on the selectivity index and the targeting index showed specific killing ability against <i>S. aureus</i>. Moreover, SFK2 showed excellent biocompatibility in mice and piglet, and demonstrated significant therapeutic efficacy against <i>S. aureus</i> infection. In conclusion, our screening of phage-derived heptapeptides effectively enhances the specific bactericidal ability of the antimicrobial peptides against <i>S. aureus</i>, providing a theoretical basis for developing targeted antimicrobial peptides.</p>","PeriodicalId":94145,"journal":{"name":"mLife","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11211671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141474097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
mLifePub Date : 2024-05-27eCollection Date: 2024-06-01DOI: 10.1002/mlf2.12124
Cristiane Thompson, Alice C Ortmann, Henk Bolhuis, Thulani Makhalanyane, Fabiano Thompson
{"title":"Harnessing marine microbiomes to develop a sustainable, all-Atlantic bioeconomy.","authors":"Cristiane Thompson, Alice C Ortmann, Henk Bolhuis, Thulani Makhalanyane, Fabiano Thompson","doi":"10.1002/mlf2.12124","DOIUrl":"10.1002/mlf2.12124","url":null,"abstract":"","PeriodicalId":94145,"journal":{"name":"mLife","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11211665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141474651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
mLifePub Date : 2024-05-27eCollection Date: 2024-06-01DOI: 10.1002/mlf2.12118
Yunxuan Guan, Di Wu, Hui Wang, Ning-Ning Liu
{"title":"Microbiome-driven anticancer therapy: A step forward from natural products.","authors":"Yunxuan Guan, Di Wu, Hui Wang, Ning-Ning Liu","doi":"10.1002/mlf2.12118","DOIUrl":"10.1002/mlf2.12118","url":null,"abstract":"<p><p>Human microbiomes, considered as a new emerging and enabling cancer hallmark, are increasingly recognized as critical effectors in cancer development and progression. Manipulation of microbiome revitalizing anticancer therapy from natural products shows promise toward improving cancer outcomes. Herein, we summarize our current understanding of the human microbiome-driven molecular mechanisms impacting cancer progression and anticancer therapy. We highlight the potential translational and clinical implications of natural products for cancer prevention and treatment by developing targeted therapeutic strategies as adjuvants for chemotherapy and immunotherapy against tumorigenesis. The challenges and opportunities for future investigations using modulation of the microbiome for cancer treatment are further discussed in this review.</p>","PeriodicalId":94145,"journal":{"name":"mLife","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11211674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141474096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}