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A fungal CYP from Beauveria bassiana with promiscuous steroid hydroxylation capabilities

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Chinese Chemical Letters 2024年第5期35卷 218-222页

作者： Yu Peng Yue Wang Tian-Jiao Chen Jing-Jing Chen Jin-Ling Yang Ting Gong Ping Zhu State Key Laboratory of Bioactive Substance and Function of natural Medicines NHC Key Laboratory of Biosynthesis of Natural ProductsCAMS Key Laboratory of Enzyme and Biocatalysis of Natural DrugsInstitute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China

Hydroxylation of steroid core is critical to the synthesis of steroid *** sp^(3) C-H hydroxylation is challenging through chemical catalysis,alternatively,fungal biotransformation offers a possible solution to this ***,mining and metabolic engineering of cytochrome P450 monooxygenases(CYPs)is usually regarded as a more eco-friendly and efficient ***,we report the mining and identification of a new steroid CYP(CYP68BE1)from Beauveria bassiana by transcriptomics,heterologous expression,in vivo and in vitro functional *** catalytic promiscuity of CYP68BE1 was explored,and CYP68BE1 showed promiscuously and catalytically versatile,which is qualified for monohydroxylation on C11α,C1α,C6βand dihydroxylation on C1β,11αand C6β,11αof six steroids,leading to the production of key steroid intermediates required in the industrial synthesis of some indispensable steroid *** dynamics simulations were performed,revealing the molecular basis of different binding orientations of CYP68BE1 with different *** discovery of CYP68BE1 offers a promising biocatalyst for enriching the steroid structural and functional diversity,which also can be applied to biosynthesize valuable steroid drug intermediates.

关键词： Fungal CYPs Steroid hydroxylase Beauveria bassiana Promiscuous biocatalyst Molecular dynamics

Novel uses of ensiled biomasses as feedstocks for green biorefineries

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Journal of Animal Science and Biotechnology 2024年第3期15卷 945-955页

作者： Marketta Rinne natural Resources institute Finland(Luke) JokioinenFinland

Perennial forage plants are efficient utilizers of solar radiation and nutrients so that there is a lot of scope to increase the production of green biomass in many ***,grasses are mainly used as feeds for ruminants and equines,but there could be higher added value use for several components of the green *** in green biorefin-ing has risen recently motivated by the increased sustainability pressures and need to break the reliance on fossil *** products derived from grass,such as paper and packaging,nanofibers,animal bedding,novel protein feeds,extracted proteins,biochemicals,nutraceuticals,bioactive compounds,biogas and biochar could create new sustainable business opportunities in rural *** green biorefinery concepts focus on using fresh green biomass as the feedstock,but preservation of it by ensiling would provide several benefits such as all-year-around avail-ability of the feedstock and increased stability of the press juice and press *** major difference between fresh and ensiled grass is the conversion of water soluble carbohydrates into fermentation end products,mainly lactic and acetic acids,that lower the pH of the silage so that it becomes stable in anaerobic *** has some important consequences on the processability and quality of products,which are partly positive and partly negative,e.g.,degradation of protein into peptides,amino acids and *** aspects are discussed in this review.

关键词： Additive Fermentation Liquid-solid separation Protein Silage

Deciphering gastric inflammation-induced tumorigenesis through multi-omics data and AI methods

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Cancer Biology & Medicine 2024年第4期21卷 312-330页

作者： Qian Zhang Mingran Yang Peng Zhang Bowen Wu Xiaosen Wei Shao Li institute for tcm-X MOE Key Laboratory of BioinformaticsBioinformatics DivisionBNRISTDepartment of AutomationTsinghua UniversityBeijing 100084China

Gastric cancer(GC), the fifth most common cancer globally, remains the leading cause of cancer deaths worldwide. Inflammation-induced tumorigenesis is the predominant process in GC development;therefore, systematic research in this area should improve understanding of the biological mechanisms that initiate GC development and promote cancer hallmarks. Here, we summarize biological knowledge regarding gastric inflammation-induced tumorigenesis, and characterize the multi-omics data and systems biology methods for investigating GC development. Of note, we highlight pioneering studies in multi-omics data and state-of-the-art network-based algorithms used for dissecting the features of gastric inflammation-induced tumorigenesis, and we propose translational applications in early GC warning biomarkers and precise treatment strategies. This review offers integrative insights for GC research, with the goal of paving the way to novel paradigms for GC precision oncology and prevention.

关键词： Gastric cancer inflammation-induced tumorigenesis multi-omics artificial intelligence network-based methods

Pd-catalyzed asymmetric carbonyl alkynylation:Synthesis of axial chiral ynones

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Chinese Chemical Letters 2024年第6期35卷 293-297页

作者： Long Jin Jian Han Dongmei Fang Min Wang Jian Liao natural products Research Center Chengdu Institute of BiologyChinese Academy of SciencesChengdu 610041China College of Chemical Engineering Sichuan UniversityChengdu 610065China University of Chinese Academy of Sciences Beijing 100049China

Ynones are important skeletons in bioactive molecules and valuable building blocks for organic synthesis,thus great efforts have been devoted to their ***,introducing prochiral substrates to construct ynones bearing a chiral framework is unrealized to ***,we reported the first example of Pd/SOP-catalyzed asymmetric carbonylative alkynylation via a non-classical carbonylative Sonogashiratype approach(acyl-Pd(Ⅱ)species generated from nucleophiles).By using cyclic diaryliodonium salts as prochiral substrates,various axial chiral ynones with good functional group tolerance(39 examples),satisfied yields(71%-96%)and excellent enantioselectivities(generally 94%-99%ee)were *** of bioactive compounds,scale-up experiment and useful transformations were also conducted to demonstrate the utility of this process.

关键词： Pd-catalyzed Axial chiral ynones Cyclic diaryliodonium High-valent palladium catalyzed Asymmetric carbonyl alkynylation

Tetramic acid-motif natural products from a marine fungus Tolypocladium cylindrosporum FB06 and their anti-Parkinson activities

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Marine Life Science & Technology 2024年第1期6卷 84-92页

作者： Yuna Jung Chaesun Kwon Taeyeon Kim Jin Woo Lee Min-Kyoo Shin Sang Hee Shim natural products Research institute College of PharmacySeoul National UniversitySeoul 08826Republic of Korea College of Pharmacy and Research institute of Pharmaceutical Sciences Seoul National UniversitySeoul 08826Republic of Korea College of Pharmacy Duksung Women’s UniversitySeoul 01369Republic of Korea

Tetramic acid-containing natural products are attracting significantly increasing attention from biologists and chemists due to their intriguing structures and biological *** the present study,two new tetramic acid alkaloids tolypyridone I(1)and tolypyridone J(2),together with five known ones(3–7),were isolated from cultures of a marine fungus Tolypocladium cylindrosporum FB06 isolate obtained from a marine sediment in Beaufort sea of North *** structures were elucidated using 1D,2D NMR,and *** configurations were established on the basis of 1H coupling constants,ROESY correlations and DP4 *** 2 was isolated as mixtures of rotational isomers with C-3 to C-7 axis between 4-hydroxy-2-pyridone and 1-ethyl-3,5-dimethylcyclohexane,hindering *** our unbiased screening to discover neuroprotective compounds in an in vitro Parkinson’s disease(PD)model,SH-SY5Y dopaminergic cells were treated with isolated compounds followed by treatment with 1-methyl-4-phenylpyridinium(MPP^(+)),a parkinsonian *** tested compounds,F-14329(7)significantly protected cells from MPP^(+)-induced ***^(+)-mediated cell death is known to be related to the regulation of Bcl-2 family proteins,specifically the down-regulation of anti-apoptotic Bcl-2 and the up-regulation of pro-apoptotic Bax *** with 2 mmol/L of MPP^(+)for 24 h significantly reduced Bcl-2 levels compared to control treated with ***,treatment with F-14329(7)attenuated such *** study demonstrates that tetramic acid-motif compounds could be potential lead compounds for treating PD.

关键词： Tolypocladium cylindrosporum Tetramic acid Tolypyridone Parkinson’s disease

Revealing the Structure-Property Difference of natural Rubber Prepared by Different Methods: Protein and Gel Content are Key Factors

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Chinese Journal of Polymer Science 2024年第4期42卷 457-467页

作者： Shao-Qi Huang Jun-Qi Zhang Yong Zhu Ling-Min Kong Lu-Sheng Liao Fu-Quan Zhang Zheng-Tian Xie Jin-Rong Wu State Key Laboratory of Polymer Materials Engineering College of Polymer Science and EngineeringSichuan UniversityChengdu610065China Hainan Provincial Key Laboratory of natural Rubber Processing Agricultural Products Processing Research Institute of Chinese Academy of Tropical Agricultural SciencesZhanjiang524001China

natural rubber (NR) is widely used in various fields including aerospace, military industry and transportation due to its superior elasticity and comprehensive mechanical properties. Nonetheless, the commercial NR prepared by different methods usually exhibits different mechanical properties, primarily due to variations in processing conditions during the conversion from latex to bulk rubber material. Consequently, this poses challenges in scientific research and industrial production of NR. In order to assess the properties of various commercially available NR and identify key structural and compositional components, this study systematically compares and analyzes four representative NR raw materials: air dried sheet (ADS), ribbed smoked sheets (RSS), constant viscidity NR (CV), and whole field latex rubber (WF). The investigation focuses on evaluating their static mechanical behavior, SIC behavior, wear resistance, and fatigue resistance. The findings indicate that protein and gel content exhibit a crucial influence on the NR properties. These constituents contribute to the formation of a high-crosslinking density region, generating a heterogeneous network structure within the rubber. This structure amplifies strains during deformation, leading to earlier and stronger strain-induced crystallization (SIC). Among the four commercial NR brands, RSS demonstrates superior overall mechanical and dynamic properties owing to its high protein and gel content. This study serves as a valuable reference for comprehending the differences in properties among various commercial NR, thereby offering guidance for the actual processing and selection of NR.

关键词： natural rubber Processingmethod Protein Gel content Property

Mechanism of action of the bile acid receptor TGR5 in obesity

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Acta Pharmaceutica Sinica B 2024年第2期14卷 468-491页

作者： Weijun Lun Qihao Yan Xinghua Guo Minchuan Zhou Yan Bai Jincan He Hua Cao Qishi Che Jiao Guo Zhengquan Su Guangdong Engineering Research Center of natural products and New Drugs Guangdong Provincial University Engineering Technology Research Center of Natural Products and DrugsGuangdong Pharmaceutical UniversityGuangzhou 510006China Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine Key Laboratory of Glucolipid Metabolic DisorderMinistry of Education of ChinaGuangdong TCM Key Laboratory for Metabolic DiseasesGuangdong Pharmaceutical UniversityGuangzhou 510006China School of Public Health Guangdong Pharmaceutical UniversityGuangzhou 510310China School of Chemistry and Chemical Engineering Guangdong Pharmaceutical UniversityZhongshan 528458China Guangzhou Rainhome Pharm&Tech Co. Ltd.Science CityGuangzhou 510663China

G protein-coupled receptors(GPCRs)are a large family of membrane protein receptors,and Takeda G protein-coupled receptor 5(TGR5)is a member of this *** a membrane receptor,TGR5 is widely distributed in different parts of the human body and plays a vital role in regulating metabolism,including the processes of energy consumption,weight loss and blood glucose *** studies have shown that TGR5 plays an important role in glucose and lipid metabolism disorders such as fatty liver,obesity and *** the global obesity situation becoming more and more serious,a comprehensive explanation of the mechanism of TGR5 and filling the gaps in knowledge concerning clinical ligand drugs are urgently *** this review,we mainly explain the anti-obesity mechanism of TGR5 to promote the further study of this target,and show the electron microscope structure of TGR5 and review recent studies on TGR5 ligands to illustrate the specific binding between TGR5 receptor binding sites and ligands,which can effectively provide new ideas for ligand research and promote drug research.

关键词： Obesity TGR5 Bile acids Ligand Appetite Metabolism GLP-1 Inflammation

CRISPR-Cas9-based genome-editing technologies in engineering bacteria for the production of plant-derived terpenoids

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Engineering Microbiology 2024年第3期4卷 43-53页

作者： Xin Sun Haobin Zhang Yuping Jia Jingyi Li Meirong Jia State Key Laboratory of Bioactive Substance and Function of natural Medicines NHC Key Laboratory of Biosynthesis of Natural ProductsCAMS Key Laboratory of Enzyme and Biocatalysis of Natural DrugsInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Shandong Academy of Pharmaceutical Sciences Jinan 250101China

Terpenoids are widely used as medicines,flavors,and ***,the use of these natural products is largely restricted by their low abundance in native ***,heterologous biosynthesis of terpenoids in microorganisms offers an alternative and sustainable approach for efficient *** genome-editing technologies have been developed for microbial strain *** regularly interspaced short palin-dromic repeats(CRISPR)-CRISPR associated protein 9(Cas9)is the most commonly used system owing to its outstanding efficiency and convenience in genome *** this review,the basic principles of CRISPR-Cas9 systems are briefly introduced and their applications in engineering bacteria for the production of plant-derived terpenoids are *** aim of this review is to provide an overview of the current developments of CRISPR-Cas9-based genome-editing technologies in bacterial engineering,concluding with perspectives on the challenges and opportunities of these technologies.

关键词： CRISPR-Cas9 Genome editing Terpenoids Metabolic engineering Bacteria

Differences in vascular endothelial function and serum proteome between obese people with phlegm-dampness constitution and balanced constitution

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Journal of Traditional Chinese Medicine 2024年第1期44卷 188-196页

作者： ZHU Linghui SUN Ziwei GUAN Yuanyuan LIU Meiyi ZHENG Yi YU Ruoxi WANG Qi LI Lingru School of Chinese Medicine Beijing University of Chinese MedicineBeijing 102488China National institute of tcm Constitution and Preventive Medicine Beijing University of Chinese MedicineBeijing 100029China

OBJECTIVE:To evaluate the extent of vascular endothelial dysfunction and preliminary identify serum protein biomarkers associated with obese individuals at risk for cardiovascular disease(CVD).METHODS:Fifteen obese volunteers with the phlegmdampness constitution or balanced constitution were recruited for this study *** clinical baseline data was collected,and the vascular endothelial function was evaluated using the EndoPAT?.Blood samples were collected for the serum proteome *** differences in the serum protein expression levels between the two groups were detected and the protein interaction network analysis,correlation analysis,receiver operating characteristic(ROC)curve analysis,and random forest model investigation were ***:There were no statistical differences found in the baseline *** vascular endothelial function,the reactive hyperemia index(RHI)of the phlegm-dampness constitution obese group was significantly lower than that of the balanced constitution obese group(1.46±0.30 vs 2.82±0.78,P<0.0001),indicating vascular endothelial *** are 66 differentially expressed serum proteins between the two *** A2(Apo A2),angiotensin-converting enzyme 2(ACE-2),interleukin-33(IL-33),and forkhead box P3(FoxP3)showed significant differences and area under curve values of their ROC curves were greater than 0.7 and correlated significantly with ***:Vascular endothelial dysfunction was present in the phlegm-dampness constitution obese ***,alterations in the expression levels of key serum proteins,including Apo A2,ACE-2,IL-33,and Fox P3 could serve as potential biomarkers in the obese population at risk of CVD.

关键词： obesity phlegm-dampness constitution vascular endothelial function proteome reactive hyperemia index