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Continuous-flow enzymatic synthesis of chiral lactones in a three-dimensional microfluidic reactor

Chinese Chemical Letters 2024年第3期35卷 299-303页

作者： Xuelei Deng Meng Fan Miao Wu Xiaoyan Zhang Ya Cheng Jianye Xia yingping zhuang Weiping Zhu Xuhong Qian Yunpeng Bai State Key Laboratory of Bioreactor Engineering Shanghai Collaborative Innovation Center for BiomanufacturingEast China University of Science and TechnologyShanghai 200237China The Extreme Optoelectromechanics Laboratory School of Physics and Materials ScienceEast China Normal UniversityShanghai 200241China Tianjin Institute of Industrial Biotechnology Chinese Academy of SciencesTianjin 300308China

A new continuous-flow process for the enzymatic synthesis of optically pureγ-lactones,which are used as flavors and fragrances in the food and cosmetic industries,was developed in a three-dimensional microfluidic *** microchannels(175 mm in length,0.9 mm in depth,and 1.72 mL in volume)were carved precisely inside a single borosilicate glass(90 mm×75 mm×12 mm)with ultrafast femtosecond laser *** flow field analysis and reaction simulation showed that the mixing of substrates and enzymes was enhanced,allowing the adjustment of residence time in a wide ***_(V4),a carbonyl reductase with excellent catalytic activity and enantioselectivity towardγ/δ-keto acids,was employed for the asymmetric synthesis of various chiral lactones.30 mmol/L(R)-γ-decalactone(3g)can be obtained in 26 s with a space-time yield(STY)up to 16,877 g L^(-1)d^(-1),which is 14.4 times higher than the highest STY of batch reaction reported *** continuous-flow process was applied to the synthesis of 6 chiral *** addition,the scaled-up synthesis of 3g was carried out in 6 cascade microreactors continuously for 6 h,demonstrating the feasibility and stability of the 3D continuous-flow process in enzymatic synthesis of optically pure compounds.

关键词： Continuous-flow Flow chemistry Microreactor Biocatalysis Carbonyl reductase Asymmetric reduction

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Resource Allocation and Computation Offloading Framework of Bio-ind ustrial IoT Based on Game Cybernetics and Stochastic Reinforcement Learning

Resource Allocation and Computation Offloading Framework of ...

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第35届中国过程控制会议

作者： He Zhang Zijian Tian yingping zhuang Guan Wang Xinggao Liu Zhejiang University State Key Laboratory of Industrial Control Technology NGICS Platform Control Department Zhejiang University School of Biotechnology East China University of Science and Technology

The Bio-industrial Internet of Things(BIoT) is promoting a new round of industrial technology revolution with its p owerful technology integration capability. Resource allocation and computation offloading within the emerging technology sys tem is the key way to achieve the goal of carbon neutrality and peak carbon dioxide emissions' dual carbon in the energy ***, most existing studies suffer from high energy consumption, high latency, and poor robustness, preventing multi-obje ctive optimization from practical applications. Given this, we first propose a novel framework named resource allocation and c omputation offloading network(RACOON) to coordinate the allocation of resources. Further, based on game cybernetics, we st udy the resource allocation and computation offloading problems and establish a stochastic game-based model. What's more, t he existence of Nash equilibrium is proved in the scene of BIoT with multi-intelligent devices. Then we propose a robust multi-agent resource allocation algorithm(RMARAA) to address this optimazation problem. Experiments show that the system can s till maintain high dynamic performance with the increase of users, and can be applied to large-scale BIoT systems.

关键词： Bio-industrial IoT Resource allocation Computation offloading Game theory Stochastic reinforcement lea rning

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Time Series Prediction in Pharmaceutical Process

Time Series Prediction in Pharmaceutical Process

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第35届中国过程控制会议

作者： Hu Xu yingping zhuang Guan Wang Changdi Li Wenhai Wang Xinggao Liu School of Biotechnology East China University of Science and Technology

The rapid growth of biomanufacturing industry, as well as its large-scale, high-speed and automated nature, have made it a key sector in manufacturing industry. Despite these advances, intelligent control of biomanufacturing processes still faces challenges, especially due to the complex, multi-scale and nonlinear characteristics of microbial and cellular metabolic *** methods struggle to accurately predict and control these processes owing to the sophisticated spatial dependencies between variables and the lack of utilization of historical data patterns, especially in the data tails, which leads to inaccurate and unsmooth predictions. In this study, we address these issues by introducing the SmoothGNN framework, which aims to enhance the accuracy and smoothness of predictions of key metrics for industrial pharmaceutical processes. Our framework consists of two key innovations: a spatial dependency learning module that automatically identifies and learns spatial dependencies between process variables, aiming to achieve accurate prediction results, and a smoothing module that intelligently handles discontinuities between predicted outcomes and historical data, thereby ensuring smooth prediction trajectories. We have validated the effectiveness of the SmoothGNN framework using real-world industrial pharmaceutical data, demonstrating that it significantly outperforms existing methods for time series prediction task.

关键词： Time Series Prediction Pharmaceutical Process Spatial Dependency Smooth Prediction

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新型PCV2衣壳融合蛋白在HEK293F细胞瞬时表达研究

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华东理工大学学报（自然科学版） 2024年第1期50卷 62-70页

作者：罗清平彭妍 ALI Mohsin 庄英萍郭美锦华东理工大学生物反应器工程国家重点实验室上海200237 上海国佳生化工程技术研究中心有限公司上海200237

猪圆环病毒2型(Porcine Circovirus type 2,PCV2)衣壳(Capsid)蛋白是制备抗猪圆环2型病毒亚单位疫苗的有效免疫抗原,能在大肠杆菌及杆状病毒/昆虫细胞表达系统中获得表达,然而在哺乳细胞中的表达研究仍然缺乏。瞬时表达条件考察结果显示... 详细信息

猪圆环病毒2型(Porcine Circovirus type 2,PCV2)衣壳(Capsid)蛋白是制备抗猪圆环2型病毒亚单位疫苗的有效免疫抗原,能在大肠杆菌及杆状病毒/昆虫细胞表达系统中获得表达,然而在哺乳细胞中的表达研究仍然缺乏。瞬时表达条件考察结果显示,采用宿主HEK293F细胞及PEI-40kDa转染试剂能获得35%病毒PCV2 Capsid基因细胞转染效率。转染试剂PEI(Polyethylenimine)与DNA比例差异会影响复合物形成大小及形态,复合物形成15~80 nm颗粒有利于转染效率的提高。实验以免疫逃逸型猪圆环病毒2b型NDSU41513病毒株,设计了新型PCV2 Capsid (△1-41aa)-Fc(pig) protein(PCFP)分子。在3 L反应器中成功实现了HEK293F细胞瞬时表达PCFP,表达水平达到3.8 mg/L。PCFP蛋白能够自主装形成约为41 nm类病毒颗粒,诱导小鼠机体内产生强烈的体液免疫反应,具有很高的应用潜力。

关键词：猪圆环病毒2型瞬时表达 HEK293F 类病毒颗粒疫苗

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Understanding the scale-up of fermentation processes from the viewpoint of the flow field in bioreactors and the physiological response of strains

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Chinese Journal of Chemical Engineering 2021年第2期34卷 178-184页

作者： Jianye Xia Guan Wang Meng Fan Min Chen Zeyu Wang yingping zhuang State Key Laboratory of Bioreactor Engineering East China University of Science and TechnologyShanghai 200237China

The production capability of a fermentation process is predominately determined by individual strains,which ultimately affected ultimately by interactions between the scale-dependent flow field developed within bioreactors and the physiological response of these *** these complicated interactions is key for better understanding the scale-up of the fermentation *** review these two aspects and address progress in strategies for scaling up fermentation processes.A perspective on how to incorporate the multiomics big data into the scale-up strategy is presented to improve the design and operation of industrial fermentation processes.

关键词： Fermentation Scale-up Bioreactors Gas-liquid flow Kinetics

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Advances in engineered Bacillus subtilis biofilms and spores, and their applications in bioremediation, biocatalysis, and biomaterials

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Synthetic and Systems Biotechnology 2021年第3期6卷 180-191页

作者： Muhammad Zubair Mohsin Rabia Omer Jiaofang Huang Ali Mohsin Meijin Guo Jiangchao Qian yingping zhuang State Key Laboratory of Bioreactor Engineering East China University of Science and TechnologyShanghai 200237PR China

Bacillus subtilis is a commonly used commercial specie with broad applications in the fields of bioengineering and *** is capable of producing both biofilms and *** are matrix-encased multicellular communities that comprise various components including exopolysaccharides,proteins,extracellular DNA,and poly-γ-glutamic *** biofilms resist environmental conditions such as oxidative stress and hence have applications in bioremediation ***,biofilms and spores can be engineered through biotechnological techniques for environmentally-friendly and safe production of bio-products such as *** ability to withstand with harsh conditions and producing spores makes Bacillus a suitable candidate for surface display *** recent years,the spores of such specie are widely used as it is generally regarded as safe to *** in synthetic biology have enabled the reprogramming of biofilms to improve their functions and enhance the production of value-added ***,there is increased interest in the production of engineered biosensors,biocatalysts,and *** elastic modulus and gel properties of *** biofilms have been utilized to develop living *** review outlines the formation of *** biofilms and *** engineering processes and their increasing application in bioremediation and biocatalysis,as well as the future directions of *** biofilm engineering,are ***,the ability of *** biofilms and spores to fabricate functional living materials with self-regenerating,self-regulating and environmentally responsive characteristics has been *** review aims to resume advances in biological engineering of *** biofilms and spores and their applications.

关键词： Bacillus subtilis Biofilms Spores Biocatalysis Bioremediation Biomaterials Synthetic biology

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甘蔗糖蜜促进类球红细菌辅酶Q_(10)的糖转化效率

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华东理工大学学报（自然科学版） 2024年第1期50卷 54-61页

作者：葛燕栗波刘爱军肖慈英陈必钦朱志春梁剑光庄英萍王泽建常州大学药学院江苏常州213164 华东理工大学生物反应器工程国家重点实验室上海200237 河北欣港药业有限公司石家庄051530 内蒙古金达威药业有限公司呼和浩特010000

考察了甘蔗糖蜜对类球红细菌发酵生产辅酶Q_(10)生物合成的影响,优化得到最佳的甘蔗糖蜜添加工艺,提升了糖转化率,大幅度降低了生产成本。不同碳源底物对辅酶Q_(10)产物合成有较大的影响,其中葡萄糖为最适碳源,利于类球红细菌菌体的生... 详细信息

考察了甘蔗糖蜜对类球红细菌发酵生产辅酶Q_(10)生物合成的影响,优化得到最佳的甘蔗糖蜜添加工艺,提升了糖转化率,大幅度降低了生产成本。不同碳源底物对辅酶Q_(10)产物合成有较大的影响,其中葡萄糖为最适碳源,利于类球红细菌菌体的生长和辅酶Q_(10)的合成。通过正交试验对辅酶Q_(10)发酵培养基进行了优化,当甘蔗糖蜜质量浓度为20 g/L、葡萄糖质量浓度为30 g/L、KH_2PO_4质量浓度为1 g/L时,对类球红细菌生长和辅酶Q_(10)合成均有利,且辅酶Q_(10)发酵效价达到了380.1 mg/L,糖转化率12.71 mg/g。在30 L发酵罐上进行发酵放大,结果辅酶Q_(10)产量最高达到3 311 mg/L,较对照组提高了15.4%,糖转化率提高了13.9%,这些发酵过程的生理参数进一步验证了甘蔗糖蜜有利于菌体代谢活力的维持以及辅酶Q_(10)的合成。

关键词：类球红细菌甘蔗糖蜜辅酶Q_(10) 发酵优化糖转化效率

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High cell density and high expression of recombinant human ApoA-I_(Milano) in Escherichia coli by twice temperature-shifted induction

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Frontiers in Biology 2006年第4期1卷 345-348页

作者： zhuang yingping MA Wenfeng GUO Meijin DING Mansheng CHU Ju ZHANG Siliang State Key Laboratory of Bioreactor Engineering National Research Center for BiotechnologyEast China University of Science and TechnologyShanghai 200237China State Key Laboratory of Bioreactor Engineering and National Research Center for Biotechnology East China University of Science and TechnologyShanghai 200237China

The effect of temperature on the formation of recombinant protein,apolipoprotein A-IMilano was investigated in the present *** temperature of the initial growth phase was set at 30ºC,while temperature variation in induction phase was arranged in three *** cell-density culture of Escherichia coli and high expression of recombinant human by twice temperature-shifted induction were carried *** results showed that ApoA-IMilano reached 4.8 g/L with the final cell density of OD600,*** was found that twice temperature-shifted induction could successfully avoid the effect of acetic acid on cell density and the expression of the *** present study provides a basic procedure for the production of recombinant ApoA-IMilano.

关键词： recombinant Escherichia coli ApoA-IMilano high density high expression twice temperature-shifted induction

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构建“合成生物学”课程群培养面向生物制造的复合型创新人才

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生物工程学报 2024年第9期40卷 3296-3304页

作者：谭高翼张立新张敬宇王启要吴辉庄英萍欧阳立明朱国良王馨叶刘雪婷华东理工大学生物工程学院上海200237

合成生物学(Synthetic Biology)作为一门新兴学科,广受关注且发展迅速,深刻影响着整个生命科学及工程技术领域的发展。与此同时,随着新工科建设的发展,加快培养复合型创新人才是对我国高等教育提出的新任务和新使命。在合成生物学蓬勃... 详细信息

合成生物学(Synthetic Biology)作为一门新兴学科,广受关注且发展迅速,深刻影响着整个生命科学及工程技术领域的发展。与此同时,随着新工科建设的发展,加快培养复合型创新人才是对我国高等教育提出的新任务和新使命。在合成生物学蓬勃发展的背景下,华东理工大学组建了以微生物药物发现和生物制造为核心内容的“合成生物学课程群”。授课团队首先对合成生物学相关的上下游课程体系进行了梳理,随后在原有课程基础上,扩充了合成生物学系列核心课程,课程群不仅涵盖了合成生物学的学科理论和前沿技术,同时锚定了上下游学科。此外,课程群还依托国家重点实验室的国内外名师讲座,并利用学科创新引智基地(“111计划”)雄厚的海外教授资源,致力于提高学生的创新能力。在课程群及授课团队的助力下,学生不仅积极参加合成生物学国际基因工程机器大赛(internationalgeneticengineering machine competition,iGEM)并连续获奖,而且有多人申请专利并参与发表科研论文等。组建合成生物学课程群为培养具有创新能力的复合型人才提供一定的示范。

关键词：合成生物学课程群复合型创新人才国际基因工程机器大赛

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Multiscale engineering of microbial cell factories: A step forward towards sustainable natural products industry

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Synthetic and Systems Biotechnology 2022年第1期7卷 586-601页

作者： Muhammad Hammad Hussain Muhammad Zubair Mohsin Waqas Qamar Zaman Junxiong Yu Xueli Zhao Yanlong Wei yingping zhuang Ali Mohsin Meijin Guo State Key Laboratory of Bioreactor Engineering East China University of Science and TechnologyShanghai200237PR China Institute of Environmental Sciences and Engineering School of Civil and Environmental EngineeringNational University of Sciences and Technology(NUST)Sector H-12Islamabad44000Pakistan

Microbial cell factories(bacteria and fungi)are the leading producers of beneficial natural products such as lycopene,carotene,herbal medicine,and biodiesel *** microorganisms are considered efficient due to their effective bioprocessing strategy(monoculture-and consortial-based approach)under distinct processing ***,the advancement in genetic and process optimization techniques leads to enhanced biosynthesis of natural products that are known functional ingredients with numerous applications in the food,cosmetic and medical *** consortia and monoculture thrive in nature in a small proportion,such as wastewater,food products,and *** similitude to natural consortia,it is possible to engineer artificial microbial consortia and program their behaviours via synthetic biology ***,this review summarizes the optimization of genetic and physicochemical parameters of the microbial system for improved production of natural ***,this review presents a brief history of natural consortium and describes the functional properties of *** review focuses on synthetic biology tools that enable new approaches to design synthetic consortia;and highlights the syntropic interactions that determine the performance and stability of synthetic *** particular,the effect of processing conditions and advanced genetic techniques to improve the productibility of both monoculture and consortial based systems have been greatly *** this context,possible strategies are also discussed to give an insight into microbial engineering for improved pro-duction of natural products in the *** summary,it is concluded that the coupling of genomic modifications with optimum physicochemical factors would be promising for producing a robust microbial cell factory that shall contribute to the increased production of natural products.

关键词： Genetic and process optimization techniques Monoculture Natural products Synthetic consortia Synthetic biology tools

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