{"title":"The role of microbiota dysbiosis in Parkinson’s disease: Pathophysiology and therapeutic opportunities","authors":"Shabnam Santos , Ivonne Salinas , Nicolás Almeida , Andrés Caicedo","doi":"10.1016/j.engmic.2025.100222","DOIUrl":"10.1016/j.engmic.2025.100222","url":null,"abstract":"<div><div>Parkinson’s disease (PD) is a chronic, progressive neurodegenerative disorder characterized by debilitating motor and non-motor symptoms. Its etiology is multifactorial, with no single definitive cause identified, although aging is a significant risk factor. Additional risks include genetic predisposition, family history, and environmental factors such as pesticide exposure and <em>Helicobacter pylori</em> infection. Dysbiosis of the gut microbiota, and in particular bacterial imbalances, has been implicated in the disruption of the gut-brain axis, contributing to both systemic and neuroinflammation. Environmental factors such as antibiotic exposure and toxins can precipitate microbial dysregulation, potentially accelerating PD progression. Understanding the mechanisms of the gut-brain axis and identifying strategies to preserve a healthy microbiome are essential for developing novel therapeutic approaches. This review synthesizes current therapeutic strategies and ongoing research focused on restoring gut-brain balance to combat PD. These approaches include fecal microbiota transplantation, dietary interventions, and probiotic therapies, all of which show promise in mitigating both motor and non-motor symptoms. Furthermore, we emphasize the urgent need for continued research into probiotics and innovative therapeutic approaches for gut-brain axis modulation, presenting novel opportunities for effective PD management.</div></div>","PeriodicalId":100478,"journal":{"name":"Engineering Microbiology","volume":"5 3","pages":"Article 100222"},"PeriodicalIF":0.0,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703538","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}
Zihan Huang, Lei Zhang, Ting Cai, Ruijun Liu, Xiaoyan Qi, Xia Wang
{"title":"Electricity generation and dibenzothiophene biodegradation using a novel electroactive bacterium Lysinibacillus macroides AP in microbial fuel cells","authors":"Zihan Huang, Lei Zhang, Ting Cai, Ruijun Liu, Xiaoyan Qi, Xia Wang","doi":"10.1016/j.engmic.2025.100221","DOIUrl":"10.1016/j.engmic.2025.100221","url":null,"abstract":"<div><div>Polycyclic aromatic sulfur heterocycles, such as dibenzothiophene (DBT), and their alkylated derivatives are recognized as persistent and toxic contaminants that pose major risks to the environment and human health. Here, a novel electroactive gram-positive bacterium, <em>Lysinibacillus macroides</em> AP, was isolated and identified from a microbial fuel cell (MFC) powered by aromatic compounds. An electricity generation performance with a maximum discharge voltage of 424.59 mV and a power density of 420.95 mW m⁻<sup>2</sup> was obtained using <em>L. macroides</em> AP in an MFC fueled with sodium formate. An analysis of the extracellular electron transfer (EET) mechanism indicated that the endogenous redox mediators produced by <em>L. macroides</em> AP were not detected, but exogenous redox mediators such as thionine acetate and anthraquinone-2, 6-disulfonate could temporarily enhance EET. The characterization of biofilm morphology revealed a dense network of microbial nanowires on the cell surface of <em>L. macroides</em> AP; the abundance of these nanowires was positively correlated with the discharge efficiency of the MFC, suggesting that the nanowires generated by <em>L. macroides</em> AP cells were likely to promote EET. Additionally, effective bioelectricity generation and simultaneous DBT degradation were successfully achieved using <em>L. macroides</em> AP in MFCs, with a power density of 385.20 mW m⁻<sup>2</sup> and 88.72 % DBT removal. This is the first report on a novel ecological role of <em>L. macroides</em> AP as a gram-positive electroactive bacterium, emphasizing its potential applications in environmental remediation and energy recovery.</div></div>","PeriodicalId":100478,"journal":{"name":"Engineering Microbiology","volume":"5 4","pages":"Article 100221"},"PeriodicalIF":0.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572628","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}
{"title":"Engineering thermotolerant microbial strains via TrRCC1 overexpression for efficient bioethanol production","authors":"Tingting Chen, Xiao He, Xinyan Zhang, Tian Tian, Jian Cheng, Tingting Long, Yonghao Li","doi":"10.1016/j.engmic.2025.100212","DOIUrl":"10.1016/j.engmic.2025.100212","url":null,"abstract":"<div><div>Efficient conversion of corn stover to bioethanol via simultaneous saccharification and fermentation (SSF) is a promising strategy for sustainable biofuel production. A major current barrier to this process is the limited thermotolerance of <em>Saccharomyces cerevisiae</em>, which hampers its performance under the high-temperature conditions required for efficient SSF. In this study, we identified <em>TrRCC1</em>, a gene from <em>Trichoderma reesei</em>, as a candidate for improving microbial stress resistance. Overexpression of <em>TrRCC1</em> in both <em>T. reesei</em> Rut C30 and <em>S. cerevisiae</em> BY4741 significantly enhanced thermotolerance. In <em>T. reesei</em> Rut C30, <em>TrRCC1</em> overexpression improved heat resistance and increased cellulase production by 2.5-fold compared to the wild-type strain. In <em>S. cerevisiae</em> BY4741, <em>TrRCC1</em> overexpression resulted in enhanced thermotolerance and a 21.8 % increase in ethanol production during SSF of corn stover. The ethanol concentration achieved in the SSF process with <em>TrRCC1</em>-overexpressing <em>S. cerevisiae</em> was 44.1 g/L, which was a notable improvement over control strain production. These findings highlight the potential of <em>TrRCC1</em> as a key gene for engineering microbial strains with improved stress resistance to enhance the efficiency of bioethanol production from lignocellulosic biomass.</div></div>","PeriodicalId":100478,"journal":{"name":"Engineering Microbiology","volume":"5 2","pages":"Article 100212"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144230932","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}
{"title":"Functional heterologous expression of the reversible Cu-decarboxylase from the lichen, Cladonia uncialis","authors":"Harman Gill, John L. Sorensen","doi":"10.1016/j.engmic.2025.100211","DOIUrl":"10.1016/j.engmic.2025.100211","url":null,"abstract":"<div><div>Despite the isolation of over 1000 known bioactive lichen mycobiont-derived secondary metabolites (SMs), understanding the genetic basis of their biosynthesis remains elusive. Biosynthetic gene clusters (BGCs) have been tentatively linked to chemical structures, with core genes such as polyketide synthases (PKSs) surrounded by accessory genes like decarboxylases. In this study, we focused on a decarboxylase gene from the genome of the lichen <em>cladonia uncialis</em> (named as <em>Cu</em>-decarboxylase) to elucidate its role in SM biosynthesis. A 963 bp gene was cloned from <em>C. uncialis</em> and expressed in <em>Escherichia coli</em> (BL21(DE3) cells using the pQE80L expression vector. The resulting 35 kDa protein was purified by applying a Ni<sup>+</sup>-NTA column using an FPLC system. Functional activity assays revealed the decarboxylation and reversible carboxylation of resorcinol to 2,4-dihydroxybenzoic acid and orcinol to orsellinic acid. This suggests a potential role for this <em>Cu</em>-decarboxylase in SM biosynthesis.</div><div>Furthermore, the lack of activity on substrates like anthranilic acid and aniline highlighted the importance of the phenolic OH group in facilitating these reactions. The 3D protein structure was predicted with AlphaFold3, based on sequence similarity with a known decarboxylases and revealed the importance of a zinc cofactor for the catalytic activity of the enzyme. The optimization of the reaction conditions, particularly for orsellinic acid production from orcinol, may enhance conversion rates and offer a viable route for industrial-scale production of bioactive compounds. This study marks the first known instance of functional heterologous expression of a non-codon-optimized gene isolated from lichen in <em>E. coli</em>.</div></div>","PeriodicalId":100478,"journal":{"name":"Engineering Microbiology","volume":"5 2","pages":"Article 100211"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144230931","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}
Maofeng Wang , Cancan Wu , Nan Liu , Xiaoqiong Jiang , Hongjie Dong , Shubao Zhao , Chaonan Li , Sujuan Xu , Lichuan Gu
{"title":"Erratum to “Regulation of protein thermal stability and its potential application in the development of thermo-attenuated vaccines” [Engineering Microbiology 4 (2024) 100162]","authors":"Maofeng Wang , Cancan Wu , Nan Liu , Xiaoqiong Jiang , Hongjie Dong , Shubao Zhao , Chaonan Li , Sujuan Xu , Lichuan Gu","doi":"10.1016/j.engmic.2025.100204","DOIUrl":"10.1016/j.engmic.2025.100204","url":null,"abstract":"","PeriodicalId":100478,"journal":{"name":"Engineering Microbiology","volume":"5 2","pages":"Article 100204"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144481428","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}
{"title":"Superoxide-mediated O2 activation drives radical cyclization in ergot alkaloid biosynthesis","authors":"Yuanyuan Jiang , Zhong Li , Shengying Li","doi":"10.1016/j.engmic.2025.100207","DOIUrl":"10.1016/j.engmic.2025.100207","url":null,"abstract":"<div><div>Conventional heme enzymes utilize iron–oxygen intermediates to activate substrates and drive reactions. Recently, Chen et al. discovered a novel NADPH-independent superoxide mechanism of heme catalase EasC, which facilitates an O<sub>2</sub>-dependent radical oxidative cyclization reaction during ergot alkaloid biosynthesis. This enzyme coordinates superoxide-mediated catalysis by connecting spatially distinct NADPH-binding pocket and heme pocket via a slender tunnel, offering a novel perspective on the catalytic mechanisms of heme enzymes in nature.</div></div>","PeriodicalId":100478,"journal":{"name":"Engineering Microbiology","volume":"5 2","pages":"Article 100207"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144203944","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}
{"title":"The Kongming defense: Host-pathogen battles take a new face","authors":"Dongchun Ni","doi":"10.1016/j.engmic.2025.100209","DOIUrl":"10.1016/j.engmic.2025.100209","url":null,"abstract":"<div><div>Bacteria employ diverse immune systems, such as CRISPR-Cas, to fend off phage infections. A recent study uncovered the unprecedented mechanistic features of the Kongming bacterial defense system, which uniquely exploits phage-derived enzymes to synthesize deoxyinosine triphosphate (dITP), thereby triggering host immunity through NAD+ depletion. In response, some phages have evolved countermeasures to disrupt dITP synthesis, highlighting the ongoing evolutionary arms race between hosts and pathogens. This discovery not only deepens our understanding of bacterial defense strategies but also paves the way for new insights in biomedical research and synthetic biology.</div></div>","PeriodicalId":100478,"journal":{"name":"Engineering Microbiology","volume":"5 2","pages":"Article 100209"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144178643","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}
Jing Li , Chengde Zhang , Shiwen Wu , Jiao Xue , Ke Chen , Zixin Deng , Dongqing Zhu
{"title":"Cytochrome P450-catalyzed allylic oxidation of pentalenene to 1-deoxypentalenic acid in pentalenolactone biosynthesis","authors":"Jing Li , Chengde Zhang , Shiwen Wu , Jiao Xue , Ke Chen , Zixin Deng , Dongqing Zhu","doi":"10.1016/j.engmic.2025.100206","DOIUrl":"10.1016/j.engmic.2025.100206","url":null,"abstract":"<div><div>Pentalenolactone is a sesquiterpene antibiotic from <em>Streptomyces</em>. Its biosynthetic pathway has been elucidated, except for the oxidation of pentalen-13-al to 1-deoxypentalenic acid. In this study, we show that cytochrome P450 pentalenene oxygenase catalyzed the formation of 1-deoxypentalenic acid. Ferredoxin XNR_5179 and ferredoxin reductase XNR_4478 from <em>S. albus</em> are suitable redox proteins for pentalenene oxygenase. The biosynthetic pathway presented fills a gap in the biosynthetic pathway of pentalenolactone and provides an example of cytochrome P450 enzyme activity being affected by redox proteins.</div></div>","PeriodicalId":100478,"journal":{"name":"Engineering Microbiology","volume":"5 2","pages":"Article 100206"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144222263","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}
Jinxin Yan , Hui Zhang , Hongxu Zhang , Hairong Yu , Wenjia Tian , Mingyuan Liu , Weikang Sun , Leilei Guo , Xiaoxu Tan , Kaiyu Gao , Tianyi Jiang , Chuanjuan Lü , Qianjin Kang , Wensi Meng , Cuiqing Ma , Chao Gao , Ping Xu
{"title":"Production of dicarboxylates from ω-amino acids using a cofactor- and co-substrate-free in vitro biosynthetic system","authors":"Jinxin Yan , Hui Zhang , Hongxu Zhang , Hairong Yu , Wenjia Tian , Mingyuan Liu , Weikang Sun , Leilei Guo , Xiaoxu Tan , Kaiyu Gao , Tianyi Jiang , Chuanjuan Lü , Qianjin Kang , Wensi Meng , Cuiqing Ma , Chao Gao , Ping Xu","doi":"10.1016/j.engmic.2025.100210","DOIUrl":"10.1016/j.engmic.2025.100210","url":null,"abstract":"<div><div>Dicarboxylates are valuable platform compounds with a broad range of applications. The <em>in vitro</em> biosynthetic system used to produce dicarboxylates from ω-amino acids via the natural pathway requires costly cofactors and co-substrates, which restricts its economic feasibility of use. In this study, we designed a cofactor- and co-substrate-free artificial pathway for the production of dicarboxylates from ω-amino acids. Only three enzymes (viz., amine oxidase from <em>Kluyveromyces marxianus</em> DMKU3-1042, xanthine oxidase from bovine milk, and catalase from <em>Aspergillus niger</em>) were required for dicarboxylate production. Succinate (0.79 g g<sup>-1</sup>), glutarate (0.83 g g<sup>-1</sup>), and adipate (0.77 g g<sup>-1</sup>) were produced in high yields from the corresponding ω-amino acids through the <em>in vitro</em> biosynthetic system with the artificial pathway. Glutarate could also be produced from <span>l</span>-lysine by further introducing <span>l</span>-lysine monooxygenase and 5-aminovaleramide amidohydrolase from <em>Pseudomonas putida</em> KT2440 into the <em>in vitro</em> biosynthetic system, with the cofactor- and co-substrate-free system achieving a product yield of 0.63 g g<sup>-1</sup>. Considering its desirable characteristics, this artificial pathway-based <em>in vitro</em> biosynthetic system may be a promising alternative for dicarboxylate production from biotechnologically produced ω-amino acids.</div></div>","PeriodicalId":100478,"journal":{"name":"Engineering Microbiology","volume":"5 3","pages":"Article 100210"},"PeriodicalIF":0.0,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144272099","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}
Minmin Hu , Shiyang Xu , Ruofei Xu , Xiangjie Qi , Xiaofeng Yu , Jinqi Wang , Yige Li , Yangyang Liu , Guiran Xi , Junbao Yu , Mei Shi
{"title":"Analysis of single-cell RNA sequencing data to examine the gastric inflammation-to-cancer transition and evaluation of the effect of probiotic on precancerous lesions","authors":"Minmin Hu , Shiyang Xu , Ruofei Xu , Xiangjie Qi , Xiaofeng Yu , Jinqi Wang , Yige Li , Yangyang Liu , Guiran Xi , Junbao Yu , Mei Shi","doi":"10.1016/j.engmic.2025.100208","DOIUrl":"10.1016/j.engmic.2025.100208","url":null,"abstract":"<div><div>Gastric cancer (GC) is the fifth most prevalent malignancy globally. However, its heterogeneity and asymptomatic early-stage development hinder timely diagnosis and effective treatment. Here, we employed single-cell RNA sequencing to delineate the transitional features of pit mucous cells (PMCs) during the gastritis-to-cancer transition and identified 100 core genes. Characterization of the gene set revealed the role of ribosomal protein small subunit and ribosomal protein large subunit in inflammation-to-cancer transition, which promoted ribonucleoprotein complex biogenesis and cytoplasmic translation. External validation using independent cohorts confirmed that this core gene set discriminated disease progression (AUC > 0.7) and was significantly enriched in GC tissues (<em>p</em> < 0.01). Moreover, we evaluated the therapeutic intervention effects of <em>C. butyricum</em> and synbiotics (Weichanghao®) using a rat model of gastritis and demonstrated the targeted suppression of inflammation-to-cancer transition genes. Our findings establish the basis for early diagnosis of GC through PMC-driven molecular dynamics. Additionally, we propose microbiota-based strategies to prevent the inflammation-to-cancer transition in preneoplastic stages. Furthermore, our results highlight that dysbiosis of the gastric microbiome can be addressed using probiotic supplementations and the core gene set may provide labeling for the evaluation of probiotics-based treatment.</div></div>","PeriodicalId":100478,"journal":{"name":"Engineering Microbiology","volume":"5 3","pages":"Article 100208"},"PeriodicalIF":0.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205430","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}