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Cobalamin-dependent radical S-adenosyl-L-methionine protein functions with a partner to successively methylate tricyclic indole alkaloid for chuangxinmycin maturation and derivatization

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Science China Chemistry 2025年第1期 308-316页

作者： Sili Wang Jiancheng Huang Yanan Du Wei Huang Yufeng Xue Xiaokun Xu Guannan Zhong Yuanyuan Shi Bin Hong Xiaoying Bian Wen Liu State Key Laboratory of Chemical Biology Shanghai Institute of Organic Chemistry University of Chinese Academy of SciencesChinese Academy of Sciences State Key Laboratory of Microbial Technology Shandong University National Health Commission (NHC) Key Laboratory of biotechnology for Microbial Drugs Institute of Medicinal BiotechnologyChinese Academy of Medical Science & Peking Union Medical College

Cobalamin(Cbl)-dependent radical S-adenosyl-L-methionine(SAM) proteins constitute the largest collection of the radical SAM superfamily that has hundreds of thousands of individual members. Many of these proteins are involved in the biosynthesis of pharmaceutically important natural products to catalyze chemically demanding reactions. In the biosynthetic pathway of chuangxinmycin(CXM), a unique indole alkaloid antibiotic with potent anti-infective activity, functionalization of the characteristic thiopyrano[4,3,2-cd]indole scaffold by regio-and stereoselective C3-methylation is believed to rely on a Cbl-dependent radical process, which, however, remained to be reconstituted biochemically. We here report the dissection of this enzymatic process, which requires the incorporation of Cxm8, a Cbl-dependent radical SAM protein, with Cxm9, a DUF5825family protein that shares no homology to any proteins of known functions. Cxm8 and Cxm9 function together by forming an unexpected heterodimeric complex that selectively catalyzes C3-methylation of the tricyclic indole-S-hetero ring system in a successive manner, achieving CXM and a recently identified, C3-dimethylated congener. Detailed biochemical characterization,isotope labeling, structural simulation and bioinformatics analysis rationalized the catalysis of the Cxm8/Cxm9 complex and particularly the necessity of the DUF5825 protein for C3-methylase activity. This is the first example that a Cbl-dependent protein acts with a partner to exhibit radical SAM activity.

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De novo synthesis of atropisomeric benzofurans via Cu/SPDO complex catalyzed asymmetric formal [3 + 2] annulation

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Science China Chemistry 2025年第1期 174-180页

作者： Fan-Xiao Meng Xing-Yu Wang Ka Lu Ju-Song Yang Fu-Min Zhang Ai-Jun Ma Bao Du Yong-Qiang Tu State Key Laboratory of Applied Organic Chemistry College of Chemistry and Chemical Engineering Lanzhou University School of Chemistry and Chemical Engineering Shanghai Jiao Tong University School of biotechnology and Health Sciences Wuyi University

Herein, the de novo synthesis of atropisomeric benzofurans through the Cu/spirocyclic-pyrrolidine-oxazoline(SPDO) complex catalyze asymmetric formal [3 + 2] cycloaddition between quinones and ynamides is explored, producing a range of structurally diverse axially chiral benzofurans in satisfactory yields with good to excellent enantioselectivities. Furthermore, density functional theory calculations were applied to explain the possible reaction mechanism.

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Genes and proteins expressed at different life cycle stages in the model protist Euplotes vannus revealed by both transcriptomic and proteomic approaches

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Science China Life Sciences 2025年第1期 232-248页

作者： Yaohan Jiang Xiao Chen Chundi Wang Liping Lyu Saleh A.Al-Farraj Naomi A.Stover Feng Gao Key Laboratory of Evolution & Marine Biodiversity (Ministry of Education) and Institute of Evolution & Marine Biodiversity Ocean University of China Marine college Shandong University Zoology Department College of ScienceKing Saud University Department of Biology Bradley University Laboratory for Marine Biology and biotechnology Qingdao Marine Science and Technology Center

Sexual reproduction first appeared in unicellular protists and has continued to be an essential biological process in almost all *** protists, which contain both germline and somatic genomes within a single cell, have evolved a special form of sexual reproduction called conjugation that involves mitosis, meiosis, fertilization, nuclear differentiation, genome rearrangement, and the development of unique cellular structures. The molecular basis and mechanisms of conjugation vary dramatically among ciliates, and many details of the process and its regulation are still largely unknown. In order to better comprehend these processes and mechanisms from an evolutionary perspective, this study provides the first comprehensive overview of the transcriptome and proteome profiles during the entire life cycle of the newly-established marine model ciliate Euplotes vannus. Transcriptome analyses from 14 life cycle stages(three vegetative stages and 11 sexual stages) revealed over 26,000 genes that are specifically expressed at different stages, many of which are related to DNA replication,transcription, translation, mitosis, meiosis, nuclear differentiation, and/or genome rearrangement. Quantitative proteomic analyses identified 338 proteins with homologs associated with conjugation and/or somatic nuclear development in other ciliates, including dicer-like proteins, Hsp90 proteins, RNA polymerase Ⅱ and transcription elongation factors, ribosomal-associated proteins, and ubiquitin-related proteins. Four of these homologs belong to the PIWI family, each with different expression patterns identified and confirmed by RT-qPCR,which may function in small RNA-mediated genome rearrangement. Proteins involved in the nonhomologous end-joining pathway are induced early during meiosis and accumulate in the developing new somatic nucleus, where more than 80% of the germline sequences are eliminated from the somatic genome. A number of new candidate genes and proteins likely t

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Synthesis and Crystal Structure of a Distorted 2D (6,3) Layer Complex, [Cd(H_2mbdpz)(N_3)_2]_n (H_2mbdpz = 4,4'-Methylenebis(3,5-dimethylpyrazole)) Containing both End-on and End-to-end Azide Bridges

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Chinese Journal of Structural Chemistry 2009年第10期28卷 1265-1269页

作者：崔广华彭献董桂英李峰峰 college of Chemical Engineering and biotechnology Hebei Polytechnic University college of Light industry Hebei Polytechnic University

The complex [Cd（H2mbdpz）（N3）2]n 1 （H2mbdpz = 4,4′-methylenebis（3,5-dimethylpyrazole）） has been hydrothermally synthesized and characterized by single-crystal X-ray diffraction analysis. It crystallizes in the monoclinic system, space groups C2/c with a = 22.154（5）, b = 7.4835（15）, c = 21.044（8）A^°,β= 115.51（3）°, V= 3148.7（17）A^°3, Z= 8, C11H16CdN10, Mr = 400.75, Dc = 1.691 g/cm^3,μ = 1.401 mm^-1, F（000） = 1599, T= 293（2） K, the final R = 0.0228 and wR = 0.0581 for 3604 observed reflections with I 〉 2σ（I）. The structural determination revealed that the coordination environment of Cd（Ⅱ） atom is a distorted octahedron consisting of two nitrogen donors of two H2mbdpz ligands and four nitrogen donors from four azide ligands. The azide moieties act as bridges in two modes： end-on （μ1,1-） and end-to-end （μ1,3-）, and H2mbdpz also serves as a bridge with a bis-monodentate coordination. Both bridging ligands link the Cd（Ⅱ） atoms to form a distorted two-dimensional （6,3） layer.

关键词： crystal structure dipyrazole ligand 2D (6,3) network cadmium(Ⅱ) complex

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基于中空二氧化锰的多功能纳米平台增强肿瘤化学动力学治疗（英文）

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Science China Materials 2025年第1期 292-302页

作者：葛德洁任德宝段亚敏罗璇何帅霖钦文君王飞印文马立新杨勇张成 State Key Laboratory of Biocatalysis and Enzyme Engineering College of Life Sciences Hubei University Hubei Key Laboratory of Industrial biotechnology College of Life Sciences Hubei University college of Health Science and Engineering Hubei University School of Materials Science and Engineering Hubei University

活性氧是肿瘤化学动力学治疗具有突出效果的关键,但是肿瘤组织缺氧和高浓度谷胱甘肽的微环境阻碍了活性氧的产生.在此,我们构建了透明质酸修饰和过氧单硫酸盐负载的中空二氧化锰纳米颗粒（HA@HMn/PMS）,其不仅可以实现肿瘤微环境响应性...

活性氧是肿瘤化学动力学治疗具有突出效果的关键,但是肿瘤组织缺氧和高浓度谷胱甘肽的微环境阻碍了活性氧的产生.在此,我们构建了透明质酸修饰和过氧单硫酸盐负载的中空二氧化锰纳米颗粒（HA@HMn/PMS）,其不仅可以实现肿瘤微环境响应性药物释放,而且还可作为活性氧供体来增强肿瘤化学动力学疗效. HA@HMn/PMS在肿瘤部位富集后,消耗局部谷胱甘肽并将二氧化锰还原为二价锰离子,然后通过类芬顿反应和催化过氧单硫酸盐分别生成·OH和·SO4-自由基.·SO4-是一种罕见的自由基,具有优异的氧化能力和非氧依赖特性,它的产生和作用打破了传统活性氧的局限性,并且可以对肿瘤细胞造成严重的损伤.在异植瘤小鼠模型中,研究表明HA@HMn/PMS能够显著抑制小鼠肿瘤生长.本研究通过结合谷胱甘肽的消耗和多种自由基在肿瘤治疗中的协同作用,激发了化学动力学治疗在多功能纳米系统应用方向的潜力.

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Highly Sensitive and Specific Monoclonal Antibody-Based Serological Methods for Rice Ragged Stunt Virus Detection in Rice Plants and Rice Brown Planthopper Vectors

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Journal of Integrative Agriculture 2014年第9期13卷 1943-1951页

作者： LIU Huan SONG Xi-jiao NI Yue-qun LU Li-na ZHOU Xue-ping WU Jian-xiang Institute of biotechnology College of Agriculture & Biotechnology Zhejiang University

Rice ragged stunt virus（RRSV） is a serious rice disease in Asia, causing serious yield losses on rice. The capsid protein（CP） gene of the major outer capsid protein of RRSV was expressed in Escherichia coli BL21（DE3） using the pMAL-C2 X expression vector. The recombinant protein was used as the immunogen to immunize BALB/c mice. A hybridoma cell line 8A12 secreting monoclonal antibody（MAb） against RRSV was obtained by fusing mouse myeloma cells（Sp 2/0） with spleen cells from the immunized BALB/c mice. Western blot analysis showed that the MAb 8A12 can specifically react with RRSV CP. Using the MAb, an antigen-coated-plate enzyme-linked immunosorbent assay（ACP-ELISA）, a dot enzyme-linked immunosorbent assay（dot-ELISA）, and immunocapture-RT-PCR（IC-RT-PCR） assay were developed to detect RRSV. The established ACP-ELISA, dot-blot ELISA and IC-RT-PCR methods could detect RRSV in infected rice tissue crude extracts with dilutions of 1：40 960, 1：1 280 and 1：655 360（w/v, g mL-1）, respectively. The ACP-ELISA and dot-blot ELISA methods could detect RRSV in infected insect vector crude extracts with dilutions of 1：12 800 and 1：1 600（an individual planthopper μL-1）, respectively. The field survey revealed that Rice ragged stunt disease occurs on rice in Hainan, Yunnan, Guangxi, Sichuan, Guizhou, Fujian, Hunan, Jiangxi and Zhejiang in China.

关键词： Rice ragged stunt virus rice brown planthopper monoclonal antibody antigen-coated-plate enzyme-linked immunosorbent assay(ACP-ELISA) dot-blot ELISA immunocapture RT-PCR

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Novel microbial fuel cell design to operate with different wastewaters simultaneously

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Journal of Environmental Sciences 2016年第4期28卷 105-111页

作者： Abhilasha Singh Mathuriya Department of biotechnology Anand Engineering College

A novel single cathode chamber and multiple anode chamber microbial fuel cell design（MAC-MFC）was developed by incorporating multiple anode chambers into a single unit and its performance was *** 60 days of operation,performance of MAC-MFC was assessed and compared with standard single anode/cathode chamber microbial fuel cell（SC-MFC）.The tests showed that MAC-MFC generated stable and higher power outputs compared with SC-MFC and each anode chamber contributed ***,MAC-MFCs were incorporated with different wastewaters in different anode chambers and their behavior in MFC performance was ***-MFC efficiently treated multiple wastewaters simultaneously at low cost and small space,which claims its candidature for future possible scale-up applications.

关键词： Microbial fuel cells Multiple wastes Bioelectricity New design Wastewater treatment

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Glycyrrhizic Acid-Targeted Carbon Nanotube Nanocomposites with Polyethylenimines-Mediated for Cancer Drug Delivery

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Journal of Donghua University(English Edition) 2017年第2期34卷 248-253页

作者：潘琪霞吴焕岭李赫宇吕瑶朱利民 college of Chemistry Chemical Engineering and BiotechnologyDonghua University Jiuzhou college of Pharmacy Yancheng Institute of Industry Technology

In order to enhance the efficiency and specificity of anticancer drug delivery and realize intelligently controlled release,a new multi-functional nanoparticle drug carrier was *** drug carrier was prepared by functionalizing multi-walled carbon nanotubes(MWCNTs) with polyethylenimines(PEI),fluorescein isothiocyanate(FITC) and glycyrrhizic acid(GL).After detailed characterization,doxorubicin(DOX) was loaded onto the obtained MWCNT composites through π-π stacking *** drug loading capacity of the GL-functionalized material was up to 92%,and the release behavior was significantly *** at pH = 5.8(typical of the tumor cell microenvironment) was much more rapid and reached a greater extent than release under normal physiological conditions(pH = 7.4).The modified MWCNTs had high biocompatibility with the liver cancer cell line SMMC-7721,but were able to induce cell death after 24 h incubation if loaded with *** with shorter incubation time(2 h) were undertaken to investigate the selectivity of the MWCNT composites,showed that the nanocomposites could specifically target cancer *** above results suggest that the functionalized carbon nanotubes-based material has potential applications for targeted delivery and controlled release of anticancer drug.

关键词： carbon nanotubes (CArTs) pH-sensitive glycyrrhizic acid(GL) targeted delivery doxorubicin (DOX)

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Thermo-Responsive Electrospun Nanofibers from Poly( N-isopropylacrylamide )/Polyvinyl Pyrrolidone Blends

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Journal of Donghua University(English Edition) 2017年第1期34卷 152-158页

作者：吕瑶吴焕岭李赫宇潘琪霞朱利民 college of Chemistry Chemical Engineering and BiotechnologyDonghua University Jiuzhou college of Pharmacy Yancheng Institute of Industry Technology

A novel nanofiber composite poly(N-isopropylacrylamide)(PNIPAAm)/polyvinyl pyrrolidone(PVP)was successfully prepared by *** medicated fibers loaded with ketoprofen(KET)as a model drug were prepared.X-ray diffraction(XRD)demonstrated that the drug was presented in the fibers with an amorphous *** scanning and transmission electron microscopy showed that the fibers had an even diameter and smooth surface,and no phase separation was *** KET loaded nanofibers did not affect the morphology of the fibers,and no drug aggregation was separated from the polymer *** contact angle measurements proved that the PNIPAAm/PVP fibers switched from hydrophilic to hydrophobic when the temperature increased the lower critical solution temperature of 32℃.In vitro drug release studies were also undertaken and the result indicated that the PNIPAAm/PVP blend nanofiber presented the properties of the two polymers,having temperature-sensitive systems with sustained release *** addition,MTT assay demonstrated that the nanofiber film was non-toxic and suitable for cell ***,the nanofiber can be used as thermoresponsive carriers for sustained release of poor water soluble drugs.

关键词： poly(N-isopropylacrylamide)(PNIPAAm) polyvinyl pyrrolidone(PVP) electrospinning drug release

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Structure and Luminescent Properties of the First Cadmium Complex with Isophthalate and Di-pyrazole Ligands

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Chinese Journal of Structural Chemistry 2011年第4期30卷 508-513页

作者：刘同飞张明熹张卫国崔广华 college of Chemical Engineering and biotechnology Hebei Polytechnic UniversityTangshan college of Light industry Hebei Polytechnic UniversityTangshan Department of Chemistry Hebei Normal University of Science and TechnologyQinhuangdao

The title complex [Cd（IPA）L（H2O）]n（1,H2IPA = isophthalic acid,L = 1,4-bis（pyra-zole-1-ylmethyl）benzene） has been hydrothermally synthesized,and characterized by elemental analyses,IR spectroscopy,TGA and X-ray single-crystal *** crystallizes in the triclinic system,space group P1 with a = 9.3060（6）,b = 10.2374（7）,c = 11.9706（8）？,α = 73.804（6）,β = 77.883（5）,γ = 85.942（5）°,V = 1070.7（1）？3,Z = 2,C22H20CdN4O5,Mr = 532.82,Dc = 1.653 g/cm3,μ = 1.062 mm-1,λ（MoKα） = 0.71073 ？,F（000） = 536,R = 0.0392 and wR = 0.0640 for 3751 observed reflections with I 2σ（I）.Crystal structure analysis showed that complex 1 has a 1D double chain structure,which is assembled together through strong O-H...O hydrogen bonding interactions between coordinated water molecules and carboxylate groups of isophthalate to form a 2D supramolecular *** addition,the solid-state fluorescent spectrum of 1 exhibits strong emission at 364 nm.

关键词： 1D double chain Cd(II) complex di-pyrazole ligand isophthalate luminescent property

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