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Enhancing the biotransformation efficiency of human CYP17A1 in Pichia pastoris by co‑expressing CPR and glucose‑6‑phosphate dehydrogenase simultaneously

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Systems Microbiology and Biomanufacturing 2024年第1期4卷 102-111页

作者： Kexin Chen Chao Liu Minglong Shao Zhenghong Xu Taowei Yang Zhiming Rao Key Laboratory of Industrial Biotechnology Ministry of EducationSchool of BiotechnologyJiangnan UniversityNo.1800 Lihu AvenueWuxi 214122JiangsuChina Laboratory of Applied Microorganisms and Metabolic Engineering School of BiotechnologyJiangnan UniversityNo.1800 Lihu AvenueWuxi 214122JiangsuChina

Steroids are a widely used class of drugs,and their hydroxylation modification has important pharmacological *** P450 is the core enzyme for hydroxylation modification of steroid molecules,but its use is significantly restricted because of low activity and poor catalytic *** the present study,we optimized the codons of the human CYP17A1(hCYP17A1)gene and performed its functional expression in Pichia pastoris *** GS115-hCYP17A1 cells exhibited activities of dual function,and the following two products were detected:17α-hydroxyprogesterone(17-HP,titer:40.12±3.16 mg/L)and androstenedione(AD,titer:4.70±0.31 mg/L).Subsequently,we compared the activity of hCYP17A1 co-expression with NADPH-cytochrome P450 oxidoreductases(CPRs)from five different strains of ***,to strengthen the NADPH regeneration system,glucose-6-phosphate dehydrogenase(G6PDH)from three different species was introduced into the pathway from progesterone to 17-HP and AD by the GS115-hCYP17A1 *** optimizing CPRs and G6PDHs,three foreign proteins were co-expressed in the host cell,namely CYP17A1,CPRYP from Yorkshire pig,and G6PDHc from Candida ***,the substrate conversion efficiency was found to be increased by 2.21-fold(46.88%)of that of the starting *** obtained a heterologous expression system with the highest biotransformation efficiency achieved to *** work provided an essential reference for the study of the introduction of crucial enzyme systems into heterologous model organisms to construct an efficient steroid biotransformation system.

关键词： Cytochrome P450 catalytic system 17α-hydroxyprogesterone Whole-cell biotransformation Cofactor recycling

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Photo-controllable antifouling hydrogels embedded with AgNPs coated spiropyran functionalized mesoporous silica for long-term antibacterial activity

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Nano Research 2024年第9期17卷 8337-8349页

作者： Wei Su Fei Wang Bing Chen Ruoke Li Jindian Liu Junjie Xu Jianhua Fan Yueling Liu State Key Laboratory of Bioreactor Engineering East China University of Science and TechnologyShanghai 200237China Department of Applied Biology School of BiotechnologyEast China University of Science and TechnologyShanghai 200237China

Silver nanoparticles(AgNPs)are widely used in antimicrobial ***,its easy aggregation and rapid loss hinder the effective *** address this issue,a novel stimuli-responsive antibacterial nanocomposite(Ag@SP-MSN)was developed based on spiropyran covalently conjugated mesoporous silica nanoparticles(284.6 nm)and AgNPs(27.1 nm)via strong electrostatic *** transmission electron microscopy(TEM)and atomic force microscopy(AFM)images proved the successful modification of AgNPs onto *** light-induced maximum loading amount towards AgNPs was calculated to be 95.0 wt.%after ultraviolet irradiation,while the amount of AgNPs released from Ag@SP-MSN was 94.4 wt.%under visible light in the aid of ammonia(0.1%,v/v).Upon cycled light irradiation,Ag@SP-MSN could recover 84.5 wt.%of AgNPs even after four *** proposed Ag@SP-MSN exhibited better antibacterial activity against both *** and *** than Ag@MSN under visible light illumination,indicating the efficient photo-responsive isomerization of ***,the Ag@SP-MSN embedded gel demonstrated outstanding antifouling ability even after 21 days when compared to AgNPs *** long-term photo-controllable antifouling property proved the excellent reversible absorption and release of Ag@SP-MSN towards *** work provides new insights into the safe utilization of nanomaterials,offering promising advancements to meet clinical antibacterial requirements.

关键词： light-responsive silver nanoparticles spiropyran mesoporous silica nanoparticles antibacterial 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68卷 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 EngineeringLanzhou UniversityLanzhou 730000China School of Chemistry and Chemical Engineering Shanghai Jiao Tong UniversityShanghai 200240China School of Biotechnology and Health Sciences Wuyi UniversityJiangmen 529020China

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 ***,density functional theory calculations were applied to explain the possible reaction mechanism.

关键词： benzofuran atropisomers novel de novo synthetic strategy asymmetric formal[3+2]cycladdition Cu/SPDO complex DFT calculations

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Targeting MDM2-p53 interaction for breast cancer therapy

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Oncology Research 2025年第4期33卷 851-861页

作者： AMJAD YOUSUF NAJEEB ULLAH KHAN Clinical Laboratory Sciences Department College of Applied Medical SciencesTaibah UniversityMadinah41477Saudi Arabia Institute of Biotechnology and Genetic Engineering The University of AgriculturePeshawarPeshawar25130Pakistan

Breast cancer is a significant global concern,with limited effective treatment ***,therapies with high efficacy and low complications,unlike the existing chemotherapies,are urgently *** address this issue,advances have been made in therapies targeting molecular pathways related to the murine double minute 2 protooncogene(MDM2)-tumor proteinp53(TP53)*** review aims to investigate the efficacy of MDM2 inhibition in restoring TP53 activity in breast cancer cells,as evidenced by clinical studies,reviews,and ***53 is a tumor suppressor and MDM2 facilitates proteasomal degradation of ***2 and TP53 activity is tightly ***,cancerous breast cells overexpress MDM2 through five hypothesized ***,TP53 levels decrease with increased tumor cell *** strategies have been identified for controlling MDM2 upregulation in cells with wild-type or mutated ***2 inhibitors(MDM2i)are administered in combination with existing chemotherapies to reduce their effects on healthy *** clinical and preclinical studies have been conducted using MDM2i,which necessitates high-quality clinical trials to support their therapeutic potential in breast cancer therapy.

关键词： Breast cancer Murine double minute 2 proto-oncogene(MDM2) Tumor protein 53(TP53) Targeted therapy

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Fibrillar adhesives with unprecedented adhesion strength,switchability and scalability

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National Science Review 2024年第10期11卷 20-33页

作者： Changhong Linghu Yangchengyi Liu Xudong Yang Dong Li Yee Yuan Tan Mohamed Haziq Bin Mohamed Hafiz Mohammad Fadhli Bin Rohani Zihao Du Jiangtao Su Yan Li Yucheng Huo Hanyan Xu Xiufeng Wang Yifan Wang Jing Yu Huajian Gao K.Jimmy Hsia School of Mechanical and Aerospace Engineering Nanyang Technological University School of Materials Science and Engineering Xiangtan University Department of Engineering Mechanics Zhejiang University School of Materials Science and Engineering Nanyang Technological University Institute of High-Performance Computing A*STAR Mechano-X Institute Applied Mechanics Laboratory Department of Engineering Mechanics Tsinghua University School of Chemistry Chemical Engineering and BiotechnologyNanyang Technological University

Bio-inspired fibrillar adhesives have received worldwide attention but their potentials have been limited by a trade-off between adhesion strength and adhesion switchability, and a size scale effect that restricts the fibrils to micro/nanoscales. Here, we report a class of adhesive fibrils that achieve unprecedented adhesion strength（～2 MPa）, switchability（～2000）, and scalability（up to millimeter-scale at the single fibril level）,by leveraging the rubber-to-glass（R2G） transition in shape memory polymers（SMPs）. Moreover, R2G SMP fibrillar adhesive arrays exhibit a switchability of >1000（with the aid of controlled buckling） and an adhesion efficiency of 57.8%, with apparent contact area scalable to 1000 mm2, outperforming existing fibrillar adhesives. We further demonstrate that the SMP fibrillar adhesives can be used as soft grippers and reusable superglue devices that are capable of holding and releasing heavy objects >2000 times of their own weight. These findings represent significant advances in smart fibrillar adhesives for numerous applications,especially those involving high-payload scenarios.

关键词： JKR-DMT transition rubber-to-glass (R2G) transition R2G fibrillar adhesives shape memory polymers adhesion switchability and scalability

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Dark-vacuole Bodies Studying by High-resolution Label-free Microscopy Assisted with Fluorescence Technology

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Chemical Research in Chinese Universities 2024年第6期40卷 978-986页

作者： LIU Xiangyu ZHANG Jinrui XU Haijiao SHAO Lina WANG Hongda State Key Laboratory of Electroanalytical Chemistry Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022P.R.China School of Applied Chemistry and Engineering University of Science and Technology of ChinaHefei 230026P.R.China Laboratory for Marine Biology and Biotechnology Qingdao National Laboratory for Marine Science and TechnologyQingdao 266237P.R.China

The intracellular logistics system,consisting of vesicles,plays a crucial role in cellular ***,there is a lack of research on the types and functions of intracellular vesicles,and new technologies are needed for further ***,researchers have discovered a new subcellular structure known as Dark-vacuole *** composition,function,and potential synergy with other organelles of these Dark-vacuole bodies remain *** this study,we utilized the high-resolution label-free Fourier ptychographic microscopy,developed by our research group,along with fluorescence confocal technology,to study and analyze Dark-vacuole *** findings provide evidence of the influence of Dark-vacuole bodies on the morphology,distribution,movement,and cell cycle of living ***,we analyzed the effects of drug induced stimulation of lipid drops and endosomes,promotion of cell endocytosis,and induction of cellular senescence on Dark-vacuole *** results indicate that Dark-vacuole bodies show little correlation with lipid drops and endocytosis vesicles,but are significantly associated with late ***,cellular senescence leads to a significant increase in the number and size of Dark-vacuole *** study serves as a foundation for further confirming the nature of Dark-vacuole bodies as new organelles.

关键词： Dark-vacuole body Subcellular Organelle Label-free Fourier ptychographic microscopy(FPM) Living cell imaging

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Development of a Mixotrophic Strategy for Efficient Cultivation of a Coccolithophore,Chrysotila roscoffensis

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Journal of Ocean University of China 2025年第2期24卷 495-505页

作者： ZHANG Luyao HE Zhichao SUN Yan LI Jian CHENG Pengfei AGATHOS Nicolas Spiros ZHOU Chengxu ZHANG Lin HAN Jichang College of Food Science and Engineering Ningbo UniversityNingbo 315832China School of Biological and Chemical Engineering Panzhihua UniversityPanzhihua 617000China Earth&Life Institute Bioengineering LaboratoryCatholic University of LouvainLouvain-La-Neuve 1348Belgium Key Laboratory of Applied Marine Biotechnology Ministry of Education of ChinaNingbo UniversityNingbo 315832China

Coccolithophores have unique ability of dual carbon fixation(photosynthesis and biocalcification)and can accumulate bioactive compounds effectively,thereby showing huge potential for CO_(2) bioremediation and simultaneous production of valueadded ***,biotechnological exploration of these microalgae is still very *** order to develop efficient cultivation strategies of these organisms,we tested the abilities of Chrysotila roscoffensis,a coccolithophore,to grow under mixotrophic and heterotrophic cultivation *** was confirmed that only glycerol stimulated the cell growth of this microalga in the presence of *** study the physiological significance of mixotrophy,we conducted cell culture experiments both autotrophically and mixotrophically,the only difference of which was optimal amount of glycerol was added under mixotrophic *** results showed that the addition of glycerol substantially enhanced the lipids and monounsaturated fatty acids accumulation of ***,but imposed slight influences on the photosynthetic capacity,pigments content,polyunsaturated fatty acids content,and *** concluded that mixotrophy might be an appropriate strategy for exploration of this species for production of high value molecules.

关键词： coccolithophores Chrysotila roscoffensis photoautotrophy mixotrophy glycerol

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Light/pH dual controlled drug release"nanocontainer"alleviates tumor hypoxia for synergistic enhanced chemotherapy,photodynamic therapy and chemodynamic therapy

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Bio-Design and Manufacturing 2024年第6期7卷 955-971页

作者： Shihe Liu Xin Zhang Zhimin Bai Yibo Yang Jia Zhang Kun Li Zhiwei Liu Ming Shi Lixin Dong Jidong Wang Jian Li Hebei Key Laboratory of Applied Chemistry Hebei Key Laboratory of NanobiotechnologyHebei Key Laboratory of Heavy Metal Deep-Remediation in Water and Resource ReuseYanshan UniversityQinhuangdao 066004China Qinhuangdao Biopha Biotechnology Co. Ltd.Qinhuangdao 066000China The First Hospital of Qinhuangdao Qinhuangdao 066000China Department of Biological Engineering College of Environment and Chemical EngineeringYanshan UniversityQinhuangdao 066004China

Photodynamic therapy(PDT)has significant advantages in treating primary ***,the hypoxic tumor microenvironment hinders the generation of sufficient reactive oxygen species during PDT to effectively kill tumor cells,further greatly limiting the applications of PDT in cancer ***,we reported a temperature/pH dual controlled drug delivery system LPC@PCN@PDA/Fe^(3+)-AS1411 based on a porous coordination network(PCN(Mn))coated with polydopamine(PDA)and modified with an aptamer AS1411.β-lapachone(LPC)was loaded inside the PCN(Mn)framework,and Fe^(3+)was attached to the surface of the PDA *** nanoparticles(NPs)exhibited excellent multimodal cancer therapeutic effects and tumor targeting ability with their photo-and chemodynamic *** therapeutic effect can be enhanced by the production of sufficient oxygen by the internal hydrogen peroxide,which improves the photodynamic effect of the photosensitizer PCN(Mn)and the chemotherapy effect ofβ-***,the conversion of Fe^(2+)to Fe^(3+)in the tumor cells exerts the Fenton effect,which generates hydroxyl radicals that cause lipid peroxidation in tumor cells and induce apoptosis,thus enhancing the chemodynamic therapeutic *** vitro and in vivo experiments revealed that the NPs demonstrated specific tumor targeting,excellent inhibition effect on tumor growth,and ***,our findings can help develop an intelligent multifunctional therapeutic nanoplatform for cancer therapy.

关键词： Porous coordination network(Mn)framework Phototherapy Photodynamic therapy Chemodynamic therapy Fenton effect

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Construction and application of high-quality genome-scale metabolic model of Zymomonas mobilis to guide rational design of microbial cell factories

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Synthetic and Systems biotechnology 2023年第3期8卷 498-508页

作者： Yalun Wu Qianqian Yuan Yongfu Yang Defei Liu Shihui Yang Hongwu Ma State Key Laboratory of Biocatalysis and Enzyme Engineering School of Life SciencesHubei UniversityWuhan430062HubeiChina Biodesign Center Key Laboratory of Systems Microbial BiotechnologyTianjin Institute of Industrial BiotechnologyChinese Academy of SciencesTianjin300308China Hubei Key Laboratory of Applied Mathematics Faculty of Mathematics and StatisticsHubei UniversityWuhan430062HubeiChina Artificial Intelligence and Knowledge Engineering Lab School of Computer Science and Information EngineeringHubei UniversityWuhan430062HubeiChina

High-quality genome-scale metabolic models(GEMs)could play critical roles on rational design of microbial cell factories in the classical Design-Build-Test-Learn cycle of synthetic biology *** of the constant establishment and update of GEMs for model microorganisms such as Escherichia coli and Saccharomyces cerevisiae,high-quality GEMs for non-model industrial microorganisms are still *** mobilis *** ZM4 is a non-model ethanologenic microorganism with many excellent industrial characteristics that has been developing as microbial cell factories for biochemical *** five GEMs of *** have been constructed,these models are either generating ATP incorrectly,or lacking information of plasmid genes,or not providing standard format *** this study,a high-quality GEM iZM516 of *** ZM4 was *** information from the improved genome annotation,literature,datasets of Biolog Phenotype Microarray studies,and recently updated Gene-Protein-Reaction information was combined for the curation of ***,516 genes,1389 reactions,1437 metabolites,and 3 cell compartments are included in iZM516,which also had the highest MEMOTE score of 91%among all published GEMs of *** growth was then predicted by iZM516,which had 79.4%agreement with the experimental results of the substrate *** addition,the potential endogenous succinate synthesis pathway of *** ZM4 was proposed through simulation and analysis using ***,metabolic engineering strategies to produce succinate and 1,4-butanediol(1,4-BDO)were designed and then simulated under anaerobic condition using *** results indicated that 1.68 mol/mol succinate and 1.07 mol/mol 1,4-BDO can be achieved through combinational metabolic engineering strategies,which was comparable to that of the model species *** study thus not only established a high-quality GEM iZM516 to help understand and design microbial cell fac

关键词： Genome-scale metabolic models(GEMSs) Non-model industrial microorganism Zymomonas mobilis Biolog phenotype microarray Succinate 1,4-Butanediol

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Comparative genomic analysis revealed that dietary habits affected the adaptation of Bifidobacterium bifidum to the intestinal tract in different geographic populations

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Food Science and Human Wellness 2024年第5期13卷 3006-3017页

作者： Min Li Jie Yu Weicheng Li Qiong Wu Jiaqi Sun Zhihong Sun Key Laboratory of Dairy Biotechnology and Engineering Inner Mongolia Agricultural UniversityMinistry of EducationInner Mongolia Agricultural UniversityHohhot 010018China Key Laboratory of Dairy Products Processing Ministry of Agriculture and Rural AffairsInner Mongolia Agricultural UniversityHohhot 010018China Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering Inner Mongolia Agricultural UniversityHohhot 010018China Collaborative Innovative Center for Lactic Acid Bacteria and Fermented Dairy Products Ministry of EducationInner Mongolia Agricultural UniversityHohhot 010018China Center for Applied Mathematics Inner Mongolia Hohhot 010018China

Recent research on the genome of Bifidobacterium bifidum has mainly focused on the isolation sources(intestinal tract niche)recently,but reports on the isolation region are *** study analyzed the differences in the genome of *** isolated from different geographical populations by comparative genomic *** at the genome level indicated that the GC content of American isolates was significantly higher than that of Chinese and Russian *** phylogenetic tree,based on 919 core genes showed that *** might be related to the geographical characteristics of isolation ***,functional annotation analysis demonstrated that copy numbers of carbohydrate-active enzymes(CAZys)involved in the degradation of polysaccharide from plant and host sources in *** were high,and 18 CAZys showed significant differences across different geographical populations,indicating that *** had adapted to the human intestinal environment,especially in the groups with diets rich in *** habits were one of the main reasons for the differences of *** across different geographical ***,*** exhibited high diversity,evident in glycoside hydrolases,the CRISPR-Cas system,and *** study provides a genetic basis for further research and development of ***.

关键词： Bifidobacterium bifidum Comparative genomics Genetic diversity Adaptation Carbohydrate-active enzymes

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