jpwen@tju.edu.cn
生物化工
新世纪优秀人才支持计划
教授
发酵法生产D-乳酸菌种选育及发酵技术开发

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生物法D-乳酸中试技术优化及万吨级工艺包开发

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发酵法生产D-乳酸菌种选育及发酵技术开发

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手性醇BOC-4生产技术的研究

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生物柴油及延伸产品关键技术开发

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达托霉素的研究开发

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他克莫司菌株动态代谢调控模型指导下途径改造

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生物原料高效转化机制与调控规律

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子囊霉素产生菌代谢途径分析及分子改造

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异丁醇基因工程菌种构建及其高效利用的基础研究

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多相复杂体系传质与生物转化规律

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恶臭废气处理

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达托霉素高产菌株的基因工程改造

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生物法小试处理马铃薯废水三级排放的生物菌群活性污泥研究

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2012合成生物学的机遇与挑战中美华人研讨会

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异丁醇合成细菌代谢通量分析及目标基因改造

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雷帕霉素产生菌基因组尺度代谢网络模型及强化研究

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废弃物资源化绿色关键技术

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生物基富马酸高效合成小试技术

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100L发酵罐中高效发酵他克莫司系列产品研发

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子囊霉素菌株合成酶的构建及调控表达机制

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生物原料高效转化机制与调控规律（后三年）

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石油烃污染土壤气相抽提-微生物降解耦合修复技术研究

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稀有放线菌诱变育种及培养条件优化
外源添加物促进微生物合成子囊霉素的方法及种子液和培养基的制备

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FK506菌株基因组尺度代谢网络模型指导下初级代谢途径改造方法

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玫瑰孢链霉菌基因工程菌的构建方法及其应用

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甲苯废气的鼓泡塔三相生物反应器净化装置及方法

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玫瑰孢链霉菌高效生产达托霉素的分批式补料发酵方法

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达托霉素生产菌玫瑰孢链霉菌的代谢网络分析方法

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甲苯废气的气升式三项环流生物反应器净化装置及方法

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一种生产D-乳酸基因工程菌及构建方法和应用

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甜高粱燃料乙醇废水环流生物反应器耦合处理装置及方法

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利用代谢轮廓分析提高雷帕霉素产量的优化发酵培养基的方法

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一种产富马酸根霉菌的发酵过程调控方法

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FK506菌株基因组尺度代谢网络模型指导下初级途径改造方法

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基于FK506生产菌筑波链霉菌基因组尺度代谢网络模型指导下次级途径改造方法

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一种基于树干毕赤酵母合成菌株发酵木糖生产富马酸的构建方法

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提高生产子囊霉素产量的基因工程菌株及构建方法

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L-乳酸脱氢酶基因缺失的工程菌及其构建方法与应用
本发明公开了外源添加物促进微生物合成子囊霉素的方法及培养基制备，属于子囊霉素的生物合成技术领域。

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本发明公开了一种FK506菌株基因组尺度代谢网络模型指导下初级途径改造方法，根据筑波链霉菌基因组序列，在添加FK506生物合成的特征反应和菌体合成反应并对网络反应进行手动精炼，获得了FK506菌株筑波链霉菌基因组尺度代谢网络模型；通过对该代谢网络模型进行分析，确定对FK506生物合成的初级途径前体关键基因。本发明改造后菌株的生产水平提高了80%-100%。为FK506菌株的初级途径前体构建、研究和分析提供了高效的指导，在FK506菌株改造的研究过程中具有很大的应用前景。

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本发明提供了玫瑰孢链霉菌基因工程菌的构建方法及其应用，克隆达托霉素合成基因簇中非核糖体蛋白合成酶(NRPS)基因下游编码ATP结合转运蛋白的三个关键基因ORF53-55，利用大肠杆菌-链霉菌穿梭质粒表达载体构建重组质粒

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本发明涉及一种甲苯废气的鼓泡塔三相生物反应器净化装置及方法，装置包括鼓泡塔三相生物反应器、缓冲罐、流量计、气泵、无机盐培养基储罐、蠕动泵和恒温电热器

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本发明涉及玫瑰孢链霉菌高效生产达托霉素的分批式补料发酵方法

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本发明涉及达托霉素生产菌玫瑰孢链霉菌的代谢网络分析方法

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甲苯废气的气升式三项环流生物反应器净化装置及方法

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本发明涉及一种生产D-乳酸基因工程菌及构建方法和应用。以L-乳酸脱氢酶基因(ldh)缺失的菌株C.glutamicum Res 167Δldh为出发菌株，过表达外源D-乳酸脱氢酶基因，获得谷氨酸棒杆菌C.glutamicum Res 167Δldh/ldhA

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本发明涉及一种甜高粱燃料乙醇废水环流生物反应器耦合处理装置及方法，包括进水泵，回流泵，厌氧内环流反应器，沉降分离区，三相分离器，中间调节槽，好氧进水泵，气升式环流反应器，固液分离区，沉降器，空气压缩机，空气流量计

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本发明提供了利用代谢轮廓分析提高雷帕霉素产量的优化发酵培养基的方法，利用动态检测和代谢轮廓分析的方法研究在初始发酵培养基和优化发酵培养基培养条件下菌体胞内代谢物动态变化及其差异

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本发明属于生物工程领域，涉及一种产富马酸根霉菌的发酵过程调控方法

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本发明公开了一种FK506菌株基因组尺度代谢网络模型指导下初级途径改造方法，根据筑波链霉菌基因组序列，在添加FK506生物合成的特征反应和菌体合成反应并对网络反应进行手动精炼，获得了FK506菌株筑波链霉菌基因组尺度代谢网络模型

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本发明公开了一种基于FK506生产菌筑波链霉菌基因组尺度代谢网络模型指导下次级途径改造方法，模型基于注释基因和生理生化信息，通过与天蓝色链霉菌基因组比较分析，发现代谢基因是高度保守的；对基因组尺度代谢网络进行代谢通量分析，模型预测了提高生产水平的突变菌次级途径基因簇改造策略。本发明采用基因组尺度代谢网络模型预测FK506菌株次级途径基因簇特殊结构基因的改造方法，改造后菌株的生产水平提高了20%？90%。

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本发明提供一株基于树干毕赤酵母合成菌株发酵木糖生产富马酸的构建方法。采用具有天然木糖代谢能力的树干毕赤酵母作为宿主，敲除树干毕赤酵母三羧酸循环中的编码富马酸酶的基因PSfum1和PSfum2，获得了富马酸酶缺失菌株；在所获得的菌株的基础上异源表达优化的富马酸还原合成模块，利用木糖发酵富马酸的酵母合成菌株；在酵母合成菌株的基础上，表达经密码子优化的来自栗酒裂殖酵母的转运蛋白YMAE，获得了发酵木糖生产富马酸的树干毕赤酵母合成菌株, 富马酸含量大于4g/L。

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本发明涉及提高生产子囊霉素产量的基因工程菌株及构建方法。基因工程菌为吸水链霉菌，保藏于中国普通微生物菌种保藏管理中心，保藏编号为CGMCC 10615。通过克隆fkbN和frr基因，利用大肠杆菌？链霉菌穿梭质粒pIB139构建fkbN和frr双基因串联过表达载体，将其转化入大肠杆菌ET12567体内，通过接合转移的方法转化吸水链霉菌子囊亚种，使过表达载体在出发菌株体内表达，构建子囊霉素基因工程菌株TD01的子囊霉素的产量达到了500mg/L，原始菌株提高了42％；具有重大的潜力和应用价值。

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本发明涉及L-乳酸脱氢酶基因缺失的工程菌及其构建方法与应用。利用PCR扩增L-乳酸脱氢酶基因(ldh)上下游序列ldh1、ldh2，并将克隆片段连接到基因敲除载体上，将构建好的敲除载体导入到谷氨酸棒杆菌中，利用同源重组的方法将菌株中的L-乳酸脱氢酶基因(ldh)沉默后筛选获得基因工程菌C.glutamicum Res167Δldh。本发明利用同源重组的方法使谷氨酸棒杆菌中L-乳酸脱氢酶基因沉默，从而得到产纯D-乳酸的基因工程菌.
Rational design of a synthetic Entner-Doudoroff pathway for enhancing glucose transformation to isobutanol in Escherichia col

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Metabolomics profiling reveals the mechanism of increased pneumocandin B-0 production by comparing mutant and parent strains

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Manipulating the expression of SARP family regulator BulZ and its target gene product to increase tacrolimus production

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Metabolomics assisted metabolic network modeling and network wide analysis of metabolites in microbiology

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Metabolic engineering of Escherichia coli for 1,3-propanediol biosynthesis from glycerol

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Metabolomic and proteomic analysis of d-lactate-producing Lactobacillus delbrueckii under various fermentation conditions

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Metabolic network model guided engineering ethylmalonyl-CoA pathway to improve ascomycin production in Streptomyces hygroscop

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Comparative proteomic and metabolomic analysis of Streptomyces tsukubaensis reveals the metabolic mechanism of FK506 overprod

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Insights into the metabolic mechanism of rapamycin overproduction in the shikimate-resistant Streptomyces hygroscopicus strai

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Engineering of the LysR family transcriptional regulator FkbR1 and its target gene to improve ascomycin production

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Combining metabolomics and network analysis to improve tacrolimus production in Streptomyces tsukubaensis using different exo

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Integration of parallel 13C-labeling experiments and in silico pathway analysis for enhanced production of ascomycin

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Integrating muti-omics analyses of Nonomuraea dietziae to reveal the role of soybean oil in [(4’-OH)MeLeu]？-CsA overproductio

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Enhancement of rapamycin production by metabolic engineering in Streptomyces hygroscopicus based on Genome-scale metabolic mo

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A genome-scale dynamic flux balance analysis model of Streptomyces tsukubaensis NRRL18488 to predict the targets for increasi

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Omics-based approach reveals phospholipids remodeling of Rhizopusoryzae responding to furfural stress for fumaric acid-produc

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Integrated intracellular metabolic profiling and pathway analysis approaches reveal complex metabolic regulation by Clostridi

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Transcriptome analysis of Rhizopus oryzae in response to xylose during fumaric acid production

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Model-driven intracellular redox status modulation for increasing isobutanol production in Escherichia coli

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A metabolic-based approach to improve xylose utilization for fumaric acid production from acid pretreated wheat bran by Rhizo

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Comparative metabolic profiling reveals the key role of amino acids metabolism in the rapamycin overproduction by Streptomyce

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Engineering Scheffersomyces stipitis for fumaric acid production from xylose

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Reduction of foaming and enhancement of ascomycin production in rational Streptomyces hygroscopicus fermentation

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Improved FK506 production by the precursors and product-tolerant mutant of Streptomyces tsukubaensis based on genome shufflin

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Enhancement of ascomycin production in Streptomyces hygroscopicus var. ascomyceticus by combining resin HP20 addition and met

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Comparative Metabolomic-Based Metabolic Mechanism Hypothesis for Microbial Mixed Cultures Utilizing Cane Molasses Wastewater

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Coupled cell morphology investigation and metabolomics analysis improves rapamycin production in Streptomyces hygroscopicus

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Analysis of ascomycin production enhanced by shikimic acid resistance and addition in Streptomyces hygroscopicus var. ascomyc

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Model-Driven Redox Pathway Manipulation for Improved Isobutanol Production in Bacillus subtilis Complemented with Experimenta

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Engineered Bacillus subtilis 168 produces l-malate by heterologous biosynthesis pathway construction and lactate dehydrogenas

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Spatial distribution characteristics of polycyclic musks as a chemical marker in river water and sediment compared with othe

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Robust aptamer sol-gel solid phase microextraction of very polar adenosine from human plasma

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Femtosecond laser-based mutagenesis strategy for micronomicin production enhancement of Micromonospora sagamiensis ATCC 21826

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Comparative metabolic profiling-based improvement of rapamycin production by Streptomyces hygroscopicus

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Engineering Bacillus subtilis for isobutanol production by heterologous Ehrlich pathway construction and the biosynthetic 2-ketoisovalerate precursor pathway overexpression

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Enhancement of FK506 production by engineering secondary pathways of Streptomyces tsukubaensis and exogenous feeding strategies

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Genome-scale metabolic network guided engineering of Streptomyces tsukubaensis for FK506 production improvement

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Enhanced FK506 production in Streptomyces tsukubaensis by rational feeding strategies based on comparative metabolic profiling analysis

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Rational medium optimization based on comparative metabolic profiling analysis to improve fumaric acid production

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Improved 2-methyl-1-propanol production in an engineered Bacillus subtilis by constructing inducible pathways

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In silico aided metabolic engineering of Streptomyces roseosporus for daptomycin yield improvement

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Rational improvement of the engineered isobutanol-producing Bacillus subtilis by elementary mode analysis

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Higher-level production of ascomycin (FK520) by Streptomyces hygroscopicus var. ascomyceticus irradiated by femtosecond laser

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Metabolic profiling of a Rhizopus oryzae fumaric acid production mutant generated by femtosecond laser irradiation

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Modeling of phenol biodegradation by Candida tropicalis immobilized in alginate gel beads

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Transient CFD modeling of toluene waste gas biodegradation in a gas-liquid-solid three-phase airlift loop reactor by immobili

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Metabolic Flux Analysis and Principal Nodes Identification for Daptomycin Production Improvement by Streptomyces roseosporus

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Enhancement of daptomycin production in Streptomyces roseosporus LC-51 by manipulation of cofactors of enzymes

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Fluid flow modeling of a gas-induced pulsating flow bubble column

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D-lactic acid production by a genetically engineered strain Corynebacterium glutamicum

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Strain Improvement of Streptomyces roseosporus for daptomycin production by rational screening of He-Ne laser and NTG induced

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Purification of high strength wastewater originated from bioethanol production with simultaneous biogas production

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Extreme-thermophilic biohydrogen production from lignocellulosic bioethanol distillery wastewater with community analysis of hydrogen-producing microflora

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CFD modeling of phenol biodegradation by immobilized Candida tropicalis in a gas-liquid-solid three-phase bubble column

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Enhancement of dihydroxyacetone production by a mutant of Gluconobacter oxydans

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Transient modeling of toluene waste gas biotreatment in a gas-liquid airlift loop reactor

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Modeling of DBT biodesulfurization by resting cells of Gordonia sp. WQ-01A immobilized in alginate gel beads in an oil-water-