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Acatulides A-G,neuroprotective macrolides from Acaulium album H-JQSF

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Chinese Chemical Letters 2024年第3期35卷 379-383页

作者： Zhi-Wu Tong Ting-Ting Wang Pei Yang Jia-Lin Sun Chen-Peng Zhang Salman Khan Xin-Cun Wang Rui-Hua Jiao Hui-Ming Ge Wen-Ying Zhuang Gang Hu Ren Xiang Tan State Key laboratory of Pharmaceutical biotechnology Institute of Functional BiomoleculesNanjing UniversityNanjing 210023China State Key laboratory Cultivation Base for TCM Quality and Efficacy Nanjing University of Chinese MedicineNanjing 210023China Insitute of microbiology Chinese Academy of SciencesBeijing 100101China

Fungal symbionts co-evolve with hosts and microbial co-inhabitants to acquire an unpredictable potential for producing novel bioactive metabolites,but the knowledge about the topic remains patchy and *** we present the chemical characterization of acatulides A-G(1-7)as architecturally unprecedented macrolides from the solid-state culture of Acaulium album H-JQSF,an arthropod-associated *** acatulide structures were elucidated by spectroscopic analysis,modified Mosher's method and single-crystal X-ray *** plausible biosynthetic pathways for compounds 1-4 are ***,acatulides B-D(2-4)and G(7)were demonstrated to be neuroprotective against the 1-methyl-4-phenylpyridinium(MPP+)-induced damage to SH-SY5Y cells and nematode Caenorhabditis elegans(***).

关键词： Acaulium album Macrolides Acatulides A–G Mosher’s method Neuroprotective

Disulfide bridge-targeted metabolome mining unravels an antiparkinsonian peptide

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Acta Pharmaceutica Sinica B 2024年第2期14卷 881-892页

作者： Zhiwu Tong Xiahong Xie Huiming Ge Ruihua Jiao Tingting Wang Xincun Wang Wenying Zhuang Gang Hu Renxiang Tan State Key laboratory of Pharmaceutical biotechnology Institute of Functional BiomoleculesSchool of Life SciencesNanjing UniversityNanjing 210023China State Key laboratory Cultivation Base for TCM Quality and Efficacy Nanjing University of Chinese MedicineNanjing 210023China Institute of microbiology Chinese Academy of SciencesBeijing 100101China

Peptides are a particular molecule class with inherent attributes of some small-molecule drugs and macromolecular biologics,thereby inspiring continuous searches for peptides with therapeutic and/or agrochemical ***,the success rate is decreasing,presumably because many interesting but less-abundant peptides are so scarce or labile that they are likely‘overlooked’during the characterization ***,we present the biochemical characterization and druggability improvement of an unprecedented minor fungal RiPP(ribosomally synthesized and post-translationally modified peptide),named acalitide,by taking the relevant advantages of metabolomics approach and disulfide-bridged substructure which is more frequently imprinted in the marketed peptide drug *** is biosynthetically unique in the macrotricyclization via two disulfide bridges and a protease(AcaB)-catalyzed lactamization of AcaA,an unprecedented precursor *** a biosynthetic logic was successfully re-edited for its sample supply renewal to facilitate the identification of the in vitro and in vivo antiparkinsonian efficacy of acalitide which was further confirmed safe and rendered brain-targetable by the liposome encapsulation *** together,the work updates the mining strategy and biosynthetic complexity of RiPPs to unravel an antiparkinsonian drug candidate valuable for combating Parkinson’s disease that is globally prevailing in an alarming manner.

关键词： Fungal RiPPs Biosynthesis Macrocyclic peptide Acalitide Antiparkinsonian

Bone marrow-derived microglia confer neuroprotection to a mouse model of amyotrophic lateral sclerosis

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Neural Regeneration Research 2024年第12期19卷 2586-2587页

作者： Beka Solomon Department of Molecular microbiology and biotechnology The Shmunis School of Biomedicine and Cancer Researchthe George S.Wise Faculty of Life Sciences Tel-Aviv UniversityRamat AvivIsrael

Amyotrophic lateral sclerosis(ALS) is a neurodegenerative disease that causes the progressive loss of both upper and lower motor neurons in the brain,brainstem,and spinal *** exact mechanisms of ALS are still unclear,but genetic and molecular studies have revealed some key factors that may contribute to motor neuron *** motor neurons,other cell types in the nervous system,such as reactive astrocytes and activated microglia,also show pathological changes and secrete harmful substances and inflammatory cytokines(Appel et al.,2011).

关键词： sclerosis brainstem

Gut liver brain axis in diseases:the implications for therapeutic interventions

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Signal Transduction and Targeted Therapy 2024年第1期9卷 79-104页

作者： Mengyao Yan Shuli Man Benyue Sun Long Ma Lanping Guo Luqi Huang Wenyuan Gao State Key laboratory of Food Nutrition and Safety Key Laboratory of Industrial MicrobiologyMinistry of EducationTianjin Key Laboratory of Industry MicrobiologyNational and Local United Engineering Lab of Metabolic Control Fermentation TechnologyChina International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal ChemistryCollege of BiotechnologyTianjin University of Science&Technology300457 TianjinChina National Resource Center for Chinese Materia Medica China Academy of Chinese Medical Sciences100700 BeijingChina Tianjin Key laboratory for Modern Drug Delivery&High-Efficiency School of Pharmaceutical Science and TechnologyTianjin UniversityWeijin Road300072 TianjinChina

Gut-liver-brain axis is a three-way highway of information interaction system among the gastrointestinal tract,liver,and nervous *** the past few decades,breakthrough progress has been made in the gut liver brain axis,mainly through understanding its formation mechanism and increasing treatment *** this review,we discuss various complex networks including barrier permeability,gut hormones,gut microbial metabolites,vagus nerve,neurotransmitters,immunity,brain toxic metabolites,β-amyloid(Aβ)metabolism,and epigenetic regulation in the gut-liver-brain *** therapies containing antibiotics,probiotics,prebiotics,synbiotics,fecal microbiota transplantation(FMT),polyphenols,low FODMAP diet and nanotechnology application regulate the gut liver brain ***,some special treatments targeting gut-liver axis include farnesoid X receptor(FXR)agonists,takeda G protein-coupled receptor 5(TGR5)agonists,glucagon-like peptide-1(GLP-1)receptor antagonists and fibroblast growth factor 19(FGF19)*** gut-brain axis embraces cognitive behavioral therapy(CBT),antidepressants and tryptophan metabolism-related *** liver-brain axis contains epigenetic regulation and Aβmetabolism-related *** the future,a better understanding of gut-liver-brain axis interactions will promote the development of novel preventative strategies and the discovery of precise therapeutic targets in multiple diseases.

关键词： metabolism therapeutic immunity

Rational protein engineering of thermostable heparinase I from Bacteroides thetaiotaomicron for highly efficient heparin degradation

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Food Science and Human Wellness 2024年

作者： Chuan Zhang Ruohan Zhao Leilei Yu Qixiao Zhai Jianxin Zhao Hao Zhang Xuegang Luo Fengwei Tian Wei Chen State Key laboratory of Food Science and Technology Jiangnan University School of Food Science and Technology Jiangnan University Key laboratory of Industrial Fermentation microbiology of the Ministry of Education & Tianjin Key Lab of Industrial microbiology College of biotechnology Tianjin University of Science and Technology National Engineering Research Center for Functional Food Jiangnan University

Heparin， a glycosaminoglycan， is a stable source of carbon that supports the growth of microorganisms in the human intestine. It is also a commonly used anticoagulant drug in clinical practice， with significant therapeutic effects. Low molecular weight heparin （LMWH） is a highly active low molecular weight fragment obtained via enzymatic reaction or the chemical degradation of heparin. LMWH has been applied globally in the prevention and treatment of venous thromboembolism in thrombosis patients. Simultaneously， as a potential prebiotic， because of its low molecular weight， LMWH can be well degraded by the gut microbiota to maintain intestinal balance. Enzymatic heparin degradation has recently emerged as a viable disposal method for LMWH preparation; however， only very few benchmark enzymes have been thoroughly described and subjected to protein engineering to improve their properties over the past few years. The commercialization of enzymes will require the development of robustly engineered enzymes that meet the demands of industrial processes. Herein， we report a rational protein engineering strategy that includes molecular dynamic simulations of flexible amino acid mutations and disulfide bond screening. Several Bt-HepI mutants were obtained and screened for high thermal stability. We obtained the Bt-HepID204C/K208C/H189W/Q198Rvariant， which features a stabilized protein surface structure， with a 1.3-fold increase in kcat/Km， a 2.44-fold increase in thermal stability at 50℃， and a 1.8-fold decrease in the average molecular weight of LMWH produced at 40℃ compared with that seen with Bt-HepIWT. Our study establishes a strategy to engineer thermostable HepI to underpin its industrial applications.

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MicroRNAs modulation in lung cancer: exploring dual mechanisms and clinical prospects

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BIOCELL 2024年第3期48卷 403-413页

作者： SHAHID HUSSAIN HABIB BOKHARI XINGXING FAN SHAUKAT IQBAL MALIK SUNDAS IJAZ MUHAMMAD ADNAN SHEREEN AIMAN FATIMA Department of biotechnology Kohsar University MurreeMurreePakistan Macao University of Science and Technology State Key laboratory of Quality Research in Chinese Medicines TaipaMacao Department of Bioinformatics and Biosciences Capital University of Science and TechnologyIslamabadPakistan Department of microbiology Kohsar University MurreeMurreePakistan

The global incidence of lung cancer is marked by a considerably elevated mortality ***(miRNAs)exert pivotal inﬂuence in the intricate orchestration of gene regulation,and their dysregulation can precipitate dire consequences,notably *** this context,miRNAs encapsulated in exosomes manifest a diversiﬁed impact on the landscape of lung cancer,wherein their actions may either foster angiogenesis,cell proliferation,and metastasis,or counteract these *** comprehensive review article discerns potential targets for the prospective development of therapeutic agents tailored for lung ***-suppressive miRNAs,such as miR-204,miR-192,miR-30a,miR-34a,miR-34b,miR-203,and miR-212,exhibit heightened expression and demonstrate the capacity to inhibit cellular proliferation and ***,the deleterious effects of tumor-promoting miRNAs like miR-21,miR-106a,miR-155,miR-205,and miR-210 can be attenuated through the application of their respective *** miRNAs selectively target various oncogenes,including NUAK Family Kinase 1(NUAK1),Snail Family Transcriptional Repressor 1(Snai1),Astrocyte elevated gene-1(AEG-1),Vimentin,Proliferation and apoptosis adaptor protein 15(PEA-15/PED),Hypoxia-inducible factor 1-alpha(HIF1),as well as tumor suppressor genes such as phosphatase and tensin homolog(PTEN),Suppressor of cytokine signaling 1(SOCS1),Tumor protein P53 binding protein 1(TP53BP1),and PH Domain and Leucine Rich Repeat Protein Phosphatase 2(PHLP22).This investigative approach proves invaluable in elucidating the speciﬁc miRNAs implicated in the deregulation of crucial genes pivotal to the pathogenesis of cancer.

关键词： miRNAs Oncogenes Tumor suppressive genes Lung cancer therapy

Dynamic changes in butyrate levels regulate satellite cell homeostasis by preventing spontaneous activation during aging

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Science China(Life Sciences) 2024年第4期67卷 745-764页

作者： Shujie Chen Liujing Huang Bingdong Liu Huimin Duan Ze Li Yifan Liu Hu Li Xiang Fu Jingchao Lin Yinlan Xu Li Liu Dan Wan Yulong Yin Liwei Xie Department of Endocrinology and Metabolism Zhujiang HospitalSouthern Medical UniversityGuangzhou 510280China State Key laboratory of Applied microbiology Southern China Guangdong Provincial Key Laboratory of Microbial Culture Collection and ApplicationGuangdong Open Laboratory of Applied MicrobiologyInstitute of MicrobiologyGuangdong Academy of SciencesGuangzhou 510070China School of Public Health Xinxiang Medical UniversityXinxiang 453003China Department of Infectious Diseases Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China Metabo-Profile biotechnology(Shanghai)Co.Ltd. Shanghai 201315China Institute of Aging Research Guangdong Provincial Key Laboratory of Medical Molecular DiagnosticsSchool of Medical TechnologyGuangdong Medical UniversityDongguan 524023China Department of Rehabilitation Medicine Nanfang HospitalSouthern Medical UniversityGuangzhou 510000China laboratory of Animal Nutritional Physiology and Metabolic Process Key Laboratory of Agro-ecological Processes in Subtropical RegionInstitute of Subtropical AgricultureChinese Academy of SciencesChangsha 410125China Bioland laboratory Guangzhou Regenerative Medicine and Health Guangdong LaboratoryGuangzhou 510005China

The gut microbiota plays a pivotal role in systemic metabolic processes and in particular functions,such as developing and preserving the skeletal muscle ***,the interplay between gut microbiota/metabolites and the regulation of satellite cell(SC)homeostasis,particularly during aging,remains *** propose that gut microbiota and its metabolites modulate SC physiology and homeostasis throughout skeletal muscle development,regeneration,and aging *** investigation reveals that microbial dysbiosis manipulated by either antibiotic treatment or fecal microbiota transplantation from aged to adult mice,leads to the activation of SCs or a significant reduction in the total ***,employing multi-omics(e.g.,RNA-seq,16S r RNA gene sequencing,and metabolomics)and bioinformatic analysis,we demonstrate that the reduced butyrate levels,alongside the gut microbial dysbiosis,could be the primary factor contributing to the reduction in the number of SCs and subsequent impairments during skeletal muscle ***,butyrate supplementation can mitigate the antibiotics-induced SC activation irrespective of gut microbiota,potentially by inhibiting the proliferation and differentiation of SCs/*** butyrate effect is likely facilitated through the monocarboxylate transporter 1(Mct1),a lactate transporter enriched on membranes of SCs and *** a result,butyrate could serve as an alternative strategy to enhance SC homeostasis and function during skeletal muscle *** findings shed light on the potential application of microbial metabolites in maintaining SC homeostasis and preventing skeletal muscle aging.

关键词： gut microbiota aging satellite cells butyrate Slc16a1(Mct1)

Asymmetric reduction of conjugated C=C bonds by immobilized fusion of old yellow enzyme and glucose dehydrogenase

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Green Synthesis and Catalysis

Green Synthesis and Catalysis 2024年第2期5卷 80-87页

作者： Yongxing Li Pengqian Luan Lele Dong Jianqiao Liu Luying Jiang Jing Bai Fufeng Liu Yanjun Jiang School of Chemical Engineering and Technology Hebei University of TechnologyTianjin 300130China College of Food Science and Biology Hebei University of Science&Technology26 Yuxiang StreetYuhua DistrictShijiazhuang 050018China Key laboratory of Industrial Fermentation microbiology of Ministry of Education Tianjin Key Laboratory of Industrial MicrobiologyCollege of BiotechnologyTianjin University of Science&TechnologyTianjin 300457China

Asymmetric reduction of the conjugated C=C bonds by the old yellow enzymes(OYEs)presents a promising field in the synthesis of chiral ***,few natural OYEs have been applied in large-scale applications due to the requirement of costly NADPH and low operational ***,a stable and efficient fusion of YqjM from Bacillus subtilis and glucose dehydrogenase(GDH)from Bacillus megaterium was constructed to stereoselectively reduce the conjugated C=C bonds in a self-sufficient continuous *** effects of the enzyme order and different linkers on the fusions were investigated by structural analysis and all-atom molecular dynamics *** best fusion YqjM_G_GDH gave 98% conversion of 100 mmol/L 2-methylcyclopentenone with an excellent ee value(>99%)in 3 h,while the mixture of individual enzymes only obtained 68% conversion after more than 8 *** improved substrate conversion of YqjM_G_GDH fusion was probably attributed to the increased flexibility of each fused enzyme and the shortening of the diffusion distance of NADPH regenerated.A one-pot process was designed to purify and immobilize the fusion on the Ni2t-nitrilotriacetic acid functionalized magnetic mesoporous silica *** resulting immobilized biocatalyst not only catalyzed the asymmetric reduction of various α,β-unsaturated ketones(20 mmol/L)continuously with only 50μmol/L NADPt to initiate the whole process,but also retained more than 82%of the initial activity after seven cycles,serving as a good candidate for the industrial applications.

关键词： Enzyme fusion Old yellowenzymes Asymmetricreduction C=C bond Cofactor regeneration Immobilization

Photoluminescence,structural and antibacterial properties of co-doped β-Ca3（PO4）2-type phosphates Ca8CuRE（PO4）7（RE=Eu-Er）

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Journal of Rare Earths 2024年第9期42卷 1658-1668页

作者： Ivan V.Nikiforov Ekaterina V.Iliin Bogdan I.Lazoryak Sergey M.Aksenov Pavel V.Slukin Dina V.Deyneko Department of Chemistry Lomonosov Moscow State University laboratory of Arctic Mineralogy and Material Sciences Kola Science CentreRussian Academy of Sciences Geological Institute Kola Science CentreRussian Academy of Sciences State Scientific Center of Applied microbiology and biotechnology of Rospotrebnadzor 24

Novel Ca8CuRE（PO4）7where RE3+=Eu3+,Tb3+,Dy3+,Ho3+and Er3+were synthesized by a solid-state method in *** structures of the samples were characterized by powder X-ray diffraction using Rietveld refinement to determine the occupation of crystal *** samples are found to have a centrosymmetric structure with space group R3c,as shown by dielectric *** synthesized Ca8CuRE（PO4）7samples have multifunctional *** Cu2+ions provide antibacterial properties,while the rare earth elements ions exhibit luminescence properties,and the β-Ca3（PO4）2-type host is *** photoluminescence properties of RE3+ions were studied and compared with other simmilar Ca8MRE（PO4）7phosphates,where M is a divalent *** photoluminescence intensity quenching in terms of energy transfer from RE3+to Cu2+is *** bioactive properties were studied in relation to antibacterial activity against *** and *** syntesized Ca8CuRE（PO4）7samples demonstrate very high and stable inhibition of bacteria *** correlation between crystal structure and properties is *** combining multiple approaches to the directio nal design of such materials,several important properties within a single chemical compound to achieve biovisualization and bioactive properties simultaneously can be combined.

关键词： Whitlockite-type structure Bioactive phosphates TCP Photoluminescence Rare earths