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Widespread and active piezotolerant microorganisms mediate phenolic compound degradation under high hydrostatic pressure in hadal trenches

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Marine Life Science & Technology 2024年第2期6卷 331-348页

作者： Hao Ling Yongxin Lv Yu Zhang Ning‑Yi Zhou Ying Xu state key laboratory of microbial metabolism Joint International Research Laboratory of Metabolic and Developmental Sciences and School of Life Sciences and BiotechnologyShanghai Jiao Tong UniversityShanghai 200240China School of Oceanography Shanghai Jiao Tong UniversityShanghai 200240China state key of laboratory of Ocean Engineering Shanghai Jiao Tong UniversityShanghai 200240China

Phenolic compounds,as well as other aromatic compounds,have been reported to be abundant in hadal *** high-throughput sequencing studies have hinted at the potential of hadal microbes to degrade these compounds,direct microbiological,genetic and biochemical evidence under in situ pressures remain ***,a microbial consortium and a pure culture of Pseudomonas,newly isolated from Mariana Trench sediments,efficiently degraded phenol under pressures up to 70 and 60 MPa,respectively,with concomitant increase in *** analyzing a high-pressure(70 MPa)culture metatranscriptome,not only was the entire range of metabolic processes under high pressure generated,but also genes encod-ing complete phenol degradation via ortho-and meta-cleavage pathways were *** isolate of Pseudomonas also contained genes encoding the complete degradation *** transcribed genes(dmpKLMNOP_(sed))were functionally identified to encode a multicomponent hydroxylase catalyzing the hydroxylation of phenol and its methylated derivatives by heterogeneous *** addition,key catabolic genes identified in the metatranscriptome of the high-pressure cultures and genomes of bacterial isolates were found to be all widely distributed in 22 published hadal microbial *** microbiological,genetic,bioinformatics,and biochemical levels,this study found that microorganisms widely found in hadal trenches were able to effectively drive phenolic compound degradation under high hydrostatic *** information will bridge a knowledge gap concerning the microbial aromatics degradation within hadal trenches.

关键词： Hadal trench High hydrostatic pressure Phenolic compounds degradation Piezotolerant microorganisms Widespread distribution

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Rational Engineering of Secondary metabolic Pathways in a Heterologous Host to Enable the Biosynthesis of Hibarimicin Derivatives with Enhanced Anti-Melanomic Activity

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Engineering 2024年第7期38卷 113-123页

作者： Xiangyang Liu Fei-Peng Zhao Tian Tian Wei-Chen Wang Zaizhou Liu Qiang Zhou Xian-Feng Hou Jing Wang Wenli Guo Shuangjun Lin Yasuhiro Igarashi Gong-Li Tang state key laboratory of Chemical Biology Shanghai Institute of Organic ChemistryUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200032China School of Chemistry and Materials Science Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China state key laboratory of microbial metabolism&joint international Research laboratory on metabolic and developmental sciences School of Life Sciences and BiotechnologyShanghai Jiao Tong UniversityShanghai 200240China Biotechnology Research Center Toyama Prefectural UniversityImizu 939-0398Japan

A 61-kb biosynthetic gene cluster(BGC),which is accountable for the biosynthesis of hibarimicin(HBM)B from Microbispora rosea *** TP-A0121,was heterologously expressed in Streptomyces coelicolor M1154,which generated a trace of the target products but accumulated a large amount of shunt *** on rational analysis of the relevant secondary metabolism,directed engineering of the biosynthetic pathways resulted in the high production of HBM B,as well as new HBM derivates with improved antitumor *** results not only establish a biosynthetic system to effectively synthesize HBMs-a class of the largest and most complex Type-Ⅱpolyketides,with a unique pseudo-dimeric structure-but also set the stage for further engineering and deep investigation of this complex biosynthetic pathway toward potent anticancer drugs.

关键词： Hibarimicin Biosynthesis Heterologous expression Biosynthetic gene cluster Rational engineering Type-II polyketide

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RsaL is a self-regulatory switch that controls alternative biosynthesis of two AHL-type quorum sensing signals in Pseudomonas aeruginosa PA1201

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mLife 2024年第1期3卷 74-86页

作者： Ya-Wen He Zi-Jing Jin Ying Cui Kai Song Bo Chen Lian Zhou state key laboratory of microbial metabolism Joint International Research Laboratory of Metabolic and Developmental SciencesSJTU-NLBP Joint R&D Centre for Biopesticides and BiofertilizersSchool of Life Sciences and BiotechnologyShanghai Jiao Tong UniversityShanghaiChina Zhiyuan Innovative Research Centre Student Innovation CentreZhiyuan CollegeShanghai Jiao Tong UniversityShanghaiChina

Pseudomonas aeruginosa is a ubiquitous and metabolically versatile microorganism naturally found in soil and *** is also an opportunistic pathogen in plants,insects,animals,and *** response to increasing cell density,*** uses two acylhomoserine lactone(AHL)quorum-sensing(QS)signals(i.e.,N-3-oxo-dodecanoyl homoserine lactone[3-oxo-C12-HSL]and Nbutanoyl-homoserine lactone[C4-HsL]),which regulate the expression of hundreds of ***,how the biosynthesis of these two QS signals is coordinated remains *** studied the regulation of these two QS signals in the rhizosphere strain ***1201 sequentially produced 3-oxo-C12-HSL and C4-HSL at the early and late growth stages,*** highest 3-oxo-C12-HSL-dependent elastase activity was observed at the early stage,while the highest C4-HSL-dependent rhamnolipid production was observed at the late *** atypical regulator RsaL played a pivotal role in coordinating 3-oxo-C12-HSL and C4-HSL biosynthesis and QS-associated *** repressed las/transcription by binding the-10 and-35 boxes of the lasl *** contrast,RsaL activated rhll transcription by binding the region encoding the 5'-untranslated region of the rhll ***,RsaL repressed its own expression by binding a nucleotide motif located in the-35 box of the rsaL ***,RsaL acts as a molecular switch that coordinates the sequential biosynthesis of AHL QS signals and differential virulence in ***,C4-HSL activation by RsaL was independent of the Las and Pseudomonas quinolone signal(PQS)QS signaling ***,we propose a new model of the QS regulatory network in PA1201,in which RsaL represents a superior player acting at the top of the hierarchy.

关键词： N-3-oxo-dodecanoyl homoserine lactone N-butanoyl-homoserine lactone Pseudomonas aeruginosa quorum sensing RsaL

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DeepSecE:A Deep-Learning-Based Framework for Multiclass Prediction of Secreted Proteins in Gram-Negative Bacteria

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Research 2024年第3期2023卷 243-257页

作者： Yumeng Zhang Jiahao Guan Chen Li Zhikang Wang Zixin Deng Robin BGasser Jiangning Song Hong-Yu Ou state key laboratory of microbial metabolism Joint International Laboratory on Metabolic&Developmental SciencesSchool of Life Sciences and BiotechnologyShanghai Jiao Tong UniversityShanghai 200240China Shanghai key laboratory of Veterinary Biotechnology Shanghai Jiao Tong UniversityShanghai 200240China Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology Monash UniversityMelbourneViC 3800Australia Monash Data Futures Institute Monash UniversityMelbourneViC 3800Australia Melbourne Veterinary School Faculty of ScienceThe University of MelbourneParkvilleVIC 3010Australia.

Proteins secreted by Gram-negative bacteria are tightly linked to the virulence and adaptability of these microbes to environmental *** identification of such secreted proteins can facilitate the investigations of infections and diseases caused by these bacterial ***,current bioinformatic methods for predicting bacterial secreted substrate proteins have limited computational efficiency and application scope on a genome-wide ***,we propose a novel deep-learning-based framework—DeepSecE—for the simultaneous inference of multiple distinct groups of secreted proteins produced by Gram-negative *** remarkably improves their classification from nonsecreted proteins using a pretrained protein language model and transformer,achieving a macro-average accuracy of 0.883 on 5-fold *** benchmarking suggests that DeepSecE achieves competitive performance with the state-of-the-art binary predictors specialized for individual types of secreted *** attention mechanism corroborates salient patterns and motifs at the N or C termini of the protein *** this pipeline,we further investigate the genome-wide prediction of novel secreted proteins and their taxonomic distribution across~1,000 Gram-negative bacterial *** present analysis demonstrates that DeepSecE has major potential for the discovery of disease-associated secreted proteins in a diverse range of Gram-negative *** online web server of DeepSecE is also publicly available to predict and explore various secreted substrate proteins via the input of bacterial genome sequences.

关键词： Deep server competitive

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The human-derived novel gut commensal Luoshenia tenuis regulates body weight and food intake in mice

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Food Science and Human Wellness 2024年第2期13卷 830-841页

作者： Yu Jiang Mengxuan Du Lisheng Xie Minzhi Jiang Yaokun Zhang Mingxia Bi Chang Liu Hongwei Liu Shuangjiang Liu state key laboratory of microbial Technology Shandong UniversityQingdao 266237China state key laboratory of microbial Resources Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China College of Life Science Hebei UniversityBaoding 071000China state key laboratory of Mycology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China

Many studies have revealed that gut microbes modulate host *** this study,we characterized the therapeutic effects of a novel gut commensal Luoshenia tenuis against host metabolic ***,by in silico analysis,we demonstrated that the *** was prevalent in the gut microbiomes of healthy humans but were depleted specifically in obesity *** in vitro cultivation revealed that *** produced short chain fatty acids that were verified to modulate host metabolism and some other volatile metabolites to benefit hosts by anti-inflammation and ***,gavage of the *** significantly decreased the body weight gain and food intake of high-fat diet-feeding C57BL/6J mice,which was in parallel with the changed expression level of genes related to satiety and feeding *** then performed the gavage trial using diet induced obese mice,and it revealed that the administration of *** alleviated significantly the abnormal glucose and lipid metabolisms and reduced the inflammatory *** summary,this study revealed a previously-unknown human gut commensal microbe that benefited host metabolism,and set the stage for the development of novel next-generation probiotic applicable for treatment of obesity and related metabolic disorders.

关键词： Luoshenia tenuis Gut microbe Feeding behavior Obesity Next-generation probiotic

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Stabilization or degradation?Post-translational modifications of JAZ proteins in plants

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Molecular Plant 2024年第7期17卷 1002-1004页

作者： Xiaoyan Xu Jianping Hu Zheng Yuan joint international Research laboratory of metabolic&developmental sciences School of Life Sciences and BiotechnologyShanghai Jiao Tong UniversityShanghai200240China Department of Energy Plant Research laboratory and Plant Biology Department Michigan State UniversityEast LansingMI 48824USA

Jasmonates(JAs)are essential hormones that regulate plant responses to biotic and abiotic stresses and are involved in various developmental processes,including flowering time control,floral organ development,and fertility of male and female gametes(Howe et al.,2018).However,our understanding of the mechanisms by which JAs integrate multiple signals to regulate diverse physiological processes remains *** the canonical JA signaling pathway,activated JAs are perceived by the F-box protein receptor CORONATINE INSENSITIVE 1(COl1),which induces the interaction between COl1 and the Jas domain of the repressor proteins JASMONATE-ZIM DOMAIN PROTEINs(JAZs),leading to the ubiquitination and degradation of JAZ *** proteolytic destruction of the JAZ repressors is a crucial step that releases the inhibition of JAZs on the JA response transcription factor MYC2,allowing MYC2 to activate the expression of downstream genes(Howe et al.,2018).Therefore,the stability and specific spatiotemporal expression pattern of the JAZ proteins are critical for the regulation of JA signaling output,as they determine the activation and repression of JA responses.

关键词： translational fertility release

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Computer-aided molecular design and optimization of potent inhibitors disrupting APC-Asef interaction

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2631-2645页

作者： Xuefei Wang Zeqian Du Yuegui Guo Jie Zhong Kun Song Junyuan Wang Jianqiang Yu Xiuyan Yang Chen-Ying Liu Ting Shi Jian Zhang Department of Pathophysiology Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of EducationShanghai Jiao Tong UniversitySchool of MedicineShanghai 200025China key laboratory of Protection Development and Utilization of Medicinal Resources in Liupanshan AreaMinistry of EducationPeptide&Protein Drug Research CenterSchool of PharmacyNingxia Medical UniversityYinchuan 750004China state key laboratory of microbial metabolism Joint International Research Laboratory of Metabolic and Developmental SciencesSchool of Life Sciences and BiotechnologyShanghai Jiao Tong UniversityShanghai 200240China Department of Colorectal and Anal Surgery Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Basic Science Research Center Base(Pharmaceutical Science) Yantai UniversityYantai 264005China Medicinal Chemistry and Bioinformatics Center Shanghai Jiao Tong UniversitySchool of MedicineShanghai 200025China state key laboratory of Pharmaceutical Biotechnology Nanjing UniversityNanjing 210023China

Colorectal cancer(CRC)is the second leading cause of cancer mortality *** initial diagnosis,approximately 20%of patients are diagnosed with metastatic CRC(mCRC).Although the APC-Asef interaction is a well-established target for mCRC therapy,the discovery and development of effective and safe drugs for mCRC patients remains an urgent and challenging *** this study,we identified a novel structural scaffold based on MAI inhibitors,the first-in-class APC-Asef inhibitors we reported *** model-driven optimizations of the N-terminal cap and experimental evaluations of inhibitory activity were performed,and 24-fold greater potency was obtained with the best inhibitor compared to the parental *** addition,the cocrystal structure validated that the two-layerπ-πstacking interactions were essential for inhibitor stabilization in the bound ***,in vitro and in vivo studies have demonstrated that novel inhibitors suppressed lung metastasis in CRC by disrupting the APC-Asef *** results provide an intrinsic structural basis to further explore drug-like molecules for APC-Asef-mediated CRC therapy.

关键词： APC-Asef Peptidomimetic Computer-aided molecular design ONIOM model π-πstacking Metastatic colorectal cancer

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Global Marine Cold Seep Metagenomes Reveal Diversity of Taxonomy,metabolic Function,and Natural Products

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Genomics, Proteomics & Bioinformatics 2024年第2期22卷 121-134页

作者： Tao Yu Yingfeng Luo Xinyu Tan Dahe Zhao Xiaochun Bi Chenji Li Yanning Zheng Hua Xiang Songnian Hu state key laboratory of microbial Resources Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of sciences Beijing 100049China

Cold seeps in the deep sea are closely linked to energy exploration as well as global climate *** alkane-dominated chemical energy-driven model makes cold seeps an oasis of deep-sea life,showcasing an unparalleled reservoir of microbial genetic ***,by analyzing 113 metagenomes collected from 14 global sites across 5 cold seep types,we present a comprehensive Cold Seep Microbiomic Database(CSMD)to archive the genomic and functional diversity of cold seep *** CSMD includes over 49 million non-redundant genes and 3175 metagenome-assembled genomes,which represent 1895 species spanning 105 *** addition,beta diversity analysis indicates that both the sampling site and cold seep type have a substantial impact on the prokaryotic microbiome community *** and anaerobic metabolisms are prevalent in microbial communities,accompanied by considerable mixotrophs and facultative anaerobes,highlighting the versatile metabolic potential in cold ***,secondary metabolic gene cluster analysis indicates that at least 98.81%of the sequences potentially encode novel natural products,with ribosomally synthesized and post-translationally modified peptides being the predominant type widely distributed in archaea and ***,the CSMD represents a valuable resource that would enhance the understanding and utilization of global cold seep microbiomes.

关键词： Global marine cold seep Metagenome Prokaryotic microbiome metabolic function Natural product

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Exercise-induced microbial changes in preventing type 2 diabetes

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Science China(Life sciences) 2024年第5期67卷 892-899页

作者： Ting Yao Hui Wang Kaiqing Lin Ruwen Wang Shanshan Guo Peijie Chen Hao Wu Tiemin Liu Ru Wang School of Exercise and Health Shanghai Frontiers Science Research Base of Exercise and Metabolic HealthShanghai University of SportShanghai 200438China Department of Physiology and Pathophysiology School of Basic Medical SciencesXi’an Jiaotong University School of MedicineXi’an 710061China Shanghai key laboratory of metabolic Remodeling and Health Institute of Metabolism&Integrative BiologyFudan UniversityShanghai 200433China state key laboratory of Genetic Engineering Human Phenome InstituteFudan Microbiome Centerand Department of Bariatric and Metabolic SurgeryHuashan HospitalFudan UniversityShanghai 201203China state key laboratory of Genetic Engineering Department of Endocrinology and MetabolismHuman Phenome Instituteand School of Life SciencesZhongshan HospitalFudan UniversityShanghai 200032China

The metabolic benefits associated with long-term physical activity are well appreciated and growing evidence suggests that it involves the gut *** we re-evaluated the link between exercise-induced microbial changes and those associated with prediabetes and *** found that the relative abundances of substantial amounts of diabetes-associated metagenomic species associated negatively with physical fitness in a Chinese athlete students *** additionally showed that those microbial changes correlated more with handgrip strength,a simple but valuable biomarker suggestive of the diabetes states,than maximum oxygen intake,one of the key surrogates for endurance ***,the causal relationships among exercise,risks for diabetes,and gut microbiota were explored based on mediation *** propose that the protective roles of exercise against type 2 diabetes are mediated,at least partly,by the gut microbiota.

关键词： gut microbiota body fat diabetes handgrip maximum oxygen intake

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Gut microbial-host-isozymes are new targets for diseases

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Science China(Life sciences) 2024年第7期67卷 1525-1527页

作者： Zhiwei Zhang Kai Wang Changtao Jiang Department of Physiology and Pathophysiology School of Basic Medical SciencesState Key Laboratory of Female Fertility PromotionCenter for Reproductive MedicinePeking UniversityBeijing 100191China Center for Obesity and metabolic Disease Research School of Basic Medical SciencesState Key Laboratory of Vascular Homeostasis and RemodelingPeking UniversityBeijing 100191China

Gut microbiota can interact with the host through lots of media including small molecular metabolites and proteins(Cani,2019;Fan and Pedersen,2021;Krautkramer et al.,2021).Recently,a new interaction pattern was identified,i.e.,gut microbiota can mimic the function of the host by producing a variety of enzymes with functions homologous to host enzymes.

关键词： diseases pattern

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