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Base editor-mediated large-scale screening of functional mutations in bacteria for industrial phenotypes

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Science China(Life Sciences) 2024年第5期67卷 1051-1060页

作者： Yaomeng Yuan Xihao Liao Shuang Li xin-hui xing Chong Zhang MOE Key Laboratory for Industrial Biocatalysis Institute of Biochemical EngineeringDepartment of Chemical EngineeringTsinghua UniversityBeijing 100084China Institute of Biopharmaceutical and Health Engineering Tsinghua Shenzhen International Graduate SchoolShenzhen 518055China Institute of Biomedical Health Technology and Engineering Shenzhen Bay LaboratoryShenzhen 440300China Center for Synthetic and Systems Biology Tsinghua UniversityBeijing 100084China

Base editing,the targeted introduction of point mutations into cellular DNA,holds promise for improving genome-scale functional genome screening to single-nucleotide *** efforts in prokaryotes,however,remain confined to loss-of-function screens using the premature stop codons-mediated gene inactivation library,which falls far short of fully releasing the potential of base ***,we developed a base editor-mediated functional single nucleotide variant screening pipeline in Escherichia *** constructed a library with 31,123 sgRNAs targeting 462 stress response-related genes in ***,and screened for adaptive mutations under isobutanol and furfural selective *** by the screening results,we successfully identified several known and novel functional *** pipeline might be expanded to the optimization of other phenotypes or the strain engineering in other microorganisms.

关键词： base editor high-throughput large-scale screening Escherichia coli functional mutation

Engineering organoid microfluidic system for biomedical and health engineering:A review

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Chinese Journal of Chemical Engineering 2021年第2期34卷 244-254页

作者： Yifan xing Junyu Liu Xiaojie Guo Haipeng Liu Wen Zeng Yi Wang Chong Zhang Yuan Lu Dong He Shaohua Ma Yonghong He xin-hui xing Key Laboratory for Industrial Biocatalysis Ministry of Education of ChinaDepartment of Chemical EngineeringTsinghua UniversityBeijing 100084China Centre for Synthetic and Systems Biology Tsinghua UniversityBeijing 100084China School of Chemical Engineering and Light Industry Guangdong University of TechnologyGuangzhou 510006China Institute of Biopharmaceutical and Health Engineering Tsinghua Shenzhen International Graduate SchoolShenzhen 518055China Institute of Biomedical Health Technology and Engineering Shenzhen Bay LaboratoryShenzhen 518055China

In recent years,organoid technology,i.e.,in vitro three-dimensional(3D)tissue culture,has attracted increasing attention in biomedical *** are cell complexes induced by differentiation of stem cells or organ-progenitor cells in vitro using 3D culture *** can replicate the key structural and functional characteristics of the target organs in *** the opening up of this new field of health engineering,there is a need for engineering-system approaches to the production,control,and quantitative analysis of organoids and their *** organoid technology has limitations,including lack of physical and chemical microenvironment control,high heterogeneity,complex manual operation,imperfect nutritional supply system,and lack of feasible online analytical technology for the *** introduction of microfluidic chip technology into organoids has overcome many of these limitations and greatly expanded the scope of *** organoid microfluidic system has become an interdisciplinary field in biomedical and health *** this review,we summarize the development and culture system of organoids,discuss how microfluidic technology has been used to solve the main technical challenges in organoid research and development,and point out new opportunities and prospects for applications of organoid microfluidic system in drug development and screening,food safety,precision medicine,and other biomedical and health engineering fields.

关键词： Organoids Stem cell Culture system Microfluidics Biomedical engineering Human health

Multi-functional engineered polypeptide-based drug delivery systems for improved cancer therapy

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Green Chemical Engineering 2023年第2期4卷 173-188页

作者： Xiaobin Li Junyu Liu Haihong Chen Yaxin Chen Yi Wang Can Yang Zhang xin-hui xing Institute of Biopharmaceutical and Health Engineering Shenzhen International Graduate SchoolTsinghua UniversityShenzhen518055China Institute of Biochemical Engineering Department of Chemical EngineeringTsinghua UniversityBeijing100084China MOE Key Laboratory for Industrial Biocatalysis Beijing100084China Institute of Biomedical Health Technology and Engineering Shenzhen Bay LaboratoryShenzhen440300China Center for Synthetic and Systems Biology Tsinghua UniversityBeijing100084China

With the rapid development of chemical engineering and biotechnology,polypeptide,as a promising candidate in the biomedical field,has been thoroughly investigated and extensively used as the drug delivery vehicle for diseases treatment,especially cancer,owing to the high biocompatibility,good biodegradability,versatile con-structions,and diverse *** polypeptide-based drug delivery system(so-called EPP-DDS)can deliver the cargos to the target site via a specific recognition effect,followed by overcoming the barriers like blood brain barrier(BBB)and releasing them by responding to the microenvironment cues,to improve the therapeutic efficacy and reduce the ***,it's of great importance to conclude and summarize the updates on EPP-DDS developed by chemical engineering *** this review,we first summarized the recent updates in the manufacturing of polypeptide and preparation of EPP-DDS based on green biochemical engineering and/or synthetic processes for cancer therapy,including chemotherapy,immunotherapy,photodynamic therapy(PDT),gene therapy,and combination ***,we surveyed the research progress of inflammation-mediated cancer treatment strategies based on EPP-DDS with high anti-inflammation ***,we concluded the discovery and green production process of engineered polypeptide,challenges,and perspectives of ***,the EPP-DDS has great potential for cancer therapy in the clinic with improved therapeutic efficacy and reduced adverse effect,which needs the innovation of green biochemical engineering for customized design and production of polypeptides.

关键词： Polypeptide Drug delivery system Cancer therapy Biopharmaceutics Green biochemical engineering

Chemical constituents,biological functions and pharmacological effects for comprehensive utilization of Eucommia ulmoides Oliver

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Food Science and Human Wellness 2019年第2期8卷 177-188页

作者： Yi-Fan xing Dong He Yi Wang Wen Zeng Chong Zhang Yuan Lu Nan Su Yan-Hua Kong xin-hui xing Key Laboratory for Industrial Biocatalysis Ministry of EducationInstitute of Biochemical EngineeringDepartment of Chemical EngineeringRoom 601Yingshi BuildingBeijing 100084China Centre for Synthetic and Systems Biology Tsinghua UniversityBeijing 100084China Animal Disease Control and Prevention Centre South Section of Hangu RoadLingbao CityHenan 472500China

Eucommia ulmoides Oliver is a native plant and valuable tonic Chinese medicine in China with a long history,great economic value and comprehensive development ***,the comprehensive utilization rate of *** *** still very low,only bark has been used as medicine and other parts of Eucommia ulmoides *** be fully utilized,even the leaves have been well utilized in food products in Japan in the past *** order to improve the comprehensive utilization efficiency of *** Oliv.,in this review,we summarized the varieties and contents of main active compounds,biological functions and pharmacological effects in different parts of *** *** findings suggest that other parts of *** *** replace the bark of *** *** some extent besides of their respective *** unique and extensive physiological functions between different parts of *** *** that the comprehensive utilization of *** *** a wide space to develop,which is also an effective way to protect *** *** and improve its the utilization rate.

关键词： Eucommia ulmoides Oliver Comprehensive utilization Chemical constituents Biological functions Pharmacological effects

Gut lumen-targeted oral delivery system for bioactive agents to regulate gut microbiome

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Journal of Future Foods 2022年第4期2卷 307-325页

作者： Junyu Liu Xiaobin Li Xiaopeng Zhang Runming Wang Sanyang Han Peiwu Qin xin-hui xing Canyang Zhang Institute of Biopharmaceutical and Health Engineering Tsinghua Shenzhen International Graduate SchoolShenzhen 518055China Institute of Biochemical Engineering Department of Chemical EngineeringKey Laboratory for Industrial BiocatalysisMinistry of EducationCenter for Synthetic and Systems BiologyTsinghua UniversityBeijing 100084China Institute of Biomedical Health Technology and Engineering Shenzhen Bay LaboratoryShenzhen 518055China

Gut microbiome(GM)is closely related to the overall health status for the human *** dysfunction of microbiome can lead to many diseases such as inflammation,cancer and neurodegenerative ***,it's of great importance to develop effective strategy to regulate *** lumen-targeted oral delivery system(GLT-ODS)has been extensively investigated and widely used in food science and engineering in these years,due to the targeted delivery property,controlled release profile,high biocompatibility and enhanced bioavailability of ***,we comprehensively summarized the current advances in GLT-ODS for bioactive ***,we systematically summarize the GLT-ODS for pre-agents(prebiotics and probiotics)and anti-agents(antibiotics and bacteriophages)according to the type of *** in-depth discussion of representative researches,we refined the limitations of existing research in carrier material and target selection,and drew a blueprint for the future technological research and *** believe that GLT-ODS will become a safe,efficient,simple and precise GM management strategy for improvement of health and shine in the development of precision food and pharmaceutical engineering in future.

关键词： Gut lumen-targeted Oral delivery systems Bioactive agents Gut microenvironment Food engineering

Nutritional and medicinal characteristics of Chinese giant salamander (Andrias davidianus) for applications in healthcare industry by artificial cultivation: A review

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Food Science and Human Wellness 2018年第1期7卷 1-10页

作者： Dong He Wenming Zhu Wen Zenga Jun Lin Yang Ji Yi Wang Chong Zhang Yuan Lu Daoquan Zhao Nan Su xin-hui xing Key Laboratory for Industrial Biocatalysis Ministry of EducationInstitute of Biochemical EngineeringDepartment of Chemical EngineeringRoom 601Yingshi BuildingBeijing100084China Centre for Synthetic and Systems Biology Tsinghua UniversityBeijing100084China Henan Academy of Aquatic Sciences No.38 Jiangshan RoadZhengzhouHenan450001China

Andrias davidianus,*** giant salamander(CGS),is one of the largest and oldest amphibians existing in the world and is also one of the valuable biological resources of *** CGS has been threatened with extinction in the past decades due to over capturing,deterioration of natural environment,the slow breeding and growth of the wild species in ***,in the past twenty years,with the breakthrough and progress of artificial breeding technology by artificial insemination,the number of artificially cultivated CGS has increased *** cultivated CGS can either be released to the CGS living environment to increase the population in nature or legally applied in food and medicinal industry as a feedstock due to the unique nutritional and medicinal values of CGS as recorded *** this review,the nutritional components,bioactive components and medicinal activities of the artificially cultivated CGS will be *** mucus,skin,meat and bone of CGS contain many different bioactive substances thereby having various medicinal activities including anti-aging,anti-fatigue,anti-tumor,therapy of burn and anti-infection and other physiological *** paper will further discuss the potential applications of the artificially cultivated CGS in healthcare industry and prospects of future technological development.

关键词： Andrias davidianus Artificial breeding Chinese giant salamander Functional foods Medicinal activity Natural resource protection Nutrition

Cross-species binding spectrum of ACE2 to SARS-CoV-2 RBD

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Science China(Life Sciences) 2023年第3期66卷 639-642页

作者： Xihao Liao Changge Guan Chenghua Wang xinjie Chen Xiaomei Lin Lianghua Lu Lu Li Ting Wang Nan Su Bian Wu xinquan Wang Chong Zhang Yi Wang Yuan Lu xin-hui xing Key Laboratory for Industrial Biocatalysis Ministry of Education of ChinaDepartment of Chemical EngineeringTsinghua UniversityBeijing 100084China College of Light Industry and Food Engineering Guangxi UniversityNanning 530004China CAS Key Laboratory of Microbial Physiological and Metabolic Engineering State Key Laboratory of Microbial ResourcesInstitute of MicrobiologyChinese Academy of SciencesBeijing 100101China The Ministry of Education Key Laboratory of Protein Science Beijing Advanced Innovation Center for Structural BiologyBeijing Frontier Research Center for Biological StructureCollaborative Innovation Center for BiotherapySchool of Life SciencesTsinghua UniversityBeijing 100084China Center for Synthetic and Systems Biology Tsinghua UniversityBeijing 100084China Institute of Biopharmaceutical and Health Engineering Tsinghua Shenzhen International Graduate SchoolShenzhen 518055China Institute of Biomedical Health Technology and Engineering Shenzhen Bay LaboratoryShenzhen 440300China

Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARSCo V-2)is the cause of COVID-19,which has posed a massive threat to human health,economy,and security worldwide(Bai et al.,2022).Genomic analysis of SARS-Co V-2 and related coronaviruses revealed that SARS-Co V and SARS-Co V-2likely had ancestors(Xu et al.,2020),which might originate in bats,followed by subsequent spread within intermediate hosts(spillover hosts)and then transmission to humans(Wang et al.,2021).

关键词： ACE2 acute

The construction of recombinant heparinase Ⅱ efficient expression system in *** and analysis of related mechanism

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The construction of recombinant heparinase Ⅱ efficient expr...

Effects of expression of heterogeneous hydrogenase in Enterobacter aerogenes and Escherichia coli on their hydrogen metabolism

The Ninth National Symposium on Enzyme Engineering

作者： Nan Su Jingjun Wu Mei Li Ye Li Xiang Mei Chong Zhang xin-hui xing Key Laboratory for Industrial Biocatalysis of Ministry of Education Institute of Biological EngineeringDepartment of Chemical EngineeringTsinghua University

＜正＞HeparinaseⅡis an important polysaccharide lyase capable of depolymerizing heparin and heparan sulfate,which has a wide use in heparin industry,but the main bottleneck for its industrial application is lack of the effective expression system and improving the enzyme thermostability which causes the high enzyme *** this study,we systematically studied the molecular design of the fusion heparinaseⅡin *** for the

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Effects of expression of heterogeneous hydrogenase in Entero...