Traditional modular design methods lead to product maintenance problems, because the module form of a system is created according to either the function requirements or the manufacturing considerations. For solving th...Traditional modular design methods lead to product maintenance problems, because the module form of a system is created according to either the function requirements or the manufacturing considerations. For solving these problems, a new modular design method is proposed with the considerations of not only the traditional function related attributes, but also the maintenance related ones. First, modularity parameters and modularity scenarios for product modularity are defined. Then the reliability and economic assessment models of product modularity strategies are formulated with the introduction of the effective working age of modules. A mathematical model used to evaluate the difference among the modules of the product so that the optimal module of the product can be established. After that, a multi-objective optimization problem based on metrics for preventive maintenance interval different degrees and preventive maintenance economics is formulated for modular optimization. Multi-objective GA is utilized to rapidly approximate the Pareto set of optimal modularity strategy trade-offs between preventive maintenance cost and preventive maintenance interval difference degree. Finally, a coordinate CNC boring machine is adopted to depict the process of product modularity. In addition, two factorial design experiments based on the modularity parameters are constructed and analyzed. These experiments investigate the impacts of these parameters on the optimal modularity strategies and the structure of module. The research proposes a new modular design method, which may help to improve the maintainability of product in modular design.展开更多
Phenolic compounds(PCs)are a group of compounds with various applications in nutraceutical,pharmaceutical and cosmetic industries.Their supply by plant extraction and chemical synthesis is often limited by low yield a...Phenolic compounds(PCs)are a group of compounds with various applications in nutraceutical,pharmaceutical and cosmetic industries.Their supply by plant extraction and chemical synthesis is often limited by low yield and high cost.Microbial production represents as a promising alternative for efficient and sustainable production of PCs.In this review,we summarize recent advances in this field,which include enzyme mining and engineering to construct artificial pathways,balance of enzyme expression to improve pathway efficiency,coculture engineering to alleviate metabolic burden and side-reactions,and the use of genetic circuits for dynamic regulation and high throughput screening.Finally,current challenges and future perspectives for efficient production of PCs are also discussed.展开更多
Vanillyl alcohol is a precursor of vanillin,which is one of the most widely used flavor compounds.Currently,vanillyl alcohol biosynthesis still encounters the problem of low efficiency.In this study,coculture engineer...Vanillyl alcohol is a precursor of vanillin,which is one of the most widely used flavor compounds.Currently,vanillyl alcohol biosynthesis still encounters the problem of low efficiency.In this study,coculture engineering was adopted to improve production efficiency of vanillyl alcohol in E.coli.First,two pathways were compared for biosynthesis of the immediate precursor 3,4-dihydroxybenzyl alcohol in monocultures,and the 3-dehydroshikimate-derived pathway showed higher efficiency than the 4-hydroxybenzoate-derived pathway.To enhance the efficiency of the last methylation step,two strategies were used,and strengthening S-adenosylmethionine(SAM)regeneration showed positive effect while strengthening SAM biosynthesis showed negative effect.Then,the optimized pathway was assembled in a single cell.However,the biosynthetic efficiency was still low,and was not significantly improved by modular optimization of pathway genes.Thus,coculturing engineering strategy was adopted.At the optimal inoculation ratio,the titer reached 328.9 mg/L.Further,gene aroE was knocked out to reduce cell growth and improve 3,4-DHBA biosynthesis of the upstream strain.As a result,the titer was improved to 559.4 mg/L in shake flasks and to 3.89 g/L in fed-batch fermentation.These are the highest reported titers of vanillyl alcohol so far.This work provides an effective strategy for sustainable production of vanillyl alcohol.展开更多
基金Supported by National Natural Science Foundation of China(Grant Nos.51205347,51322506)Zhejiang Provincial Natural Science Foundation of China(Grant No.LR14E050003)+3 种基金Project of National Science and Technology Plan of China(Grant No.2013IM030500)Fundamental Research Funds for the Central Universities of ChinaInnovation Foundation of the State Key Laboratory of Fluid Power Transmission and Control of ChinaZhejiang University K.P.Chao’s High Technology Development Foundation of China
文摘Traditional modular design methods lead to product maintenance problems, because the module form of a system is created according to either the function requirements or the manufacturing considerations. For solving these problems, a new modular design method is proposed with the considerations of not only the traditional function related attributes, but also the maintenance related ones. First, modularity parameters and modularity scenarios for product modularity are defined. Then the reliability and economic assessment models of product modularity strategies are formulated with the introduction of the effective working age of modules. A mathematical model used to evaluate the difference among the modules of the product so that the optimal module of the product can be established. After that, a multi-objective optimization problem based on metrics for preventive maintenance interval different degrees and preventive maintenance economics is formulated for modular optimization. Multi-objective GA is utilized to rapidly approximate the Pareto set of optimal modularity strategy trade-offs between preventive maintenance cost and preventive maintenance interval difference degree. Finally, a coordinate CNC boring machine is adopted to depict the process of product modularity. In addition, two factorial design experiments based on the modularity parameters are constructed and analyzed. These experiments investigate the impacts of these parameters on the optimal modularity strategies and the structure of module. The research proposes a new modular design method, which may help to improve the maintainability of product in modular design.
基金This work was supported by National Key Research and Development Program of China(2018YFA0901800 and 2018YFA0901400)National Natural Science Foundation of China(21978015,21636001,and 21776008).
文摘Phenolic compounds(PCs)are a group of compounds with various applications in nutraceutical,pharmaceutical and cosmetic industries.Their supply by plant extraction and chemical synthesis is often limited by low yield and high cost.Microbial production represents as a promising alternative for efficient and sustainable production of PCs.In this review,we summarize recent advances in this field,which include enzyme mining and engineering to construct artificial pathways,balance of enzyme expression to improve pathway efficiency,coculture engineering to alleviate metabolic burden and side-reactions,and the use of genetic circuits for dynamic regulation and high throughput screening.Finally,current challenges and future perspectives for efficient production of PCs are also discussed.
基金supported by National Key Research and Development Program of China(2018YFA0901800)National Natural Science Foundation of China(21978015)Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project(TSBICIP-KJGG-009).
文摘Vanillyl alcohol is a precursor of vanillin,which is one of the most widely used flavor compounds.Currently,vanillyl alcohol biosynthesis still encounters the problem of low efficiency.In this study,coculture engineering was adopted to improve production efficiency of vanillyl alcohol in E.coli.First,two pathways were compared for biosynthesis of the immediate precursor 3,4-dihydroxybenzyl alcohol in monocultures,and the 3-dehydroshikimate-derived pathway showed higher efficiency than the 4-hydroxybenzoate-derived pathway.To enhance the efficiency of the last methylation step,two strategies were used,and strengthening S-adenosylmethionine(SAM)regeneration showed positive effect while strengthening SAM biosynthesis showed negative effect.Then,the optimized pathway was assembled in a single cell.However,the biosynthetic efficiency was still low,and was not significantly improved by modular optimization of pathway genes.Thus,coculturing engineering strategy was adopted.At the optimal inoculation ratio,the titer reached 328.9 mg/L.Further,gene aroE was knocked out to reduce cell growth and improve 3,4-DHBA biosynthesis of the upstream strain.As a result,the titer was improved to 559.4 mg/L in shake flasks and to 3.89 g/L in fed-batch fermentation.These are the highest reported titers of vanillyl alcohol so far.This work provides an effective strategy for sustainable production of vanillyl alcohol.