Greenhouse cultivation has evolved from simple covered rows of open-fields crops to highly sophisticated controlled environment agriculture(CEA)facilities that projected the image of plant factories for urban agricult...Greenhouse cultivation has evolved from simple covered rows of open-fields crops to highly sophisticated controlled environment agriculture(CEA)facilities that projected the image of plant factories for urban agriculture.The advances and improvements in CEA have promoted the scientific solutions for the efficient production of plants in populated cities and multi-story buildings.Successful deployment of CEA for urban agriculture requires many components and subsystems,as well as the understanding of the external influencing factors that should be systematically considered and integrated.This review is an attempt to highlight some of the most recent advances in greenhouse technology and CEA in order to raise the awareness for technology transfer and adaptation,which is necessary for a successful transition to urban agriculture.This study reviewed several aspects of a high-tech CEA system including improvements in the frame and covering materials,environment perception and data sharing,and advanced microclimate control and energy optimization models.This research highlighted urban agriculture and its derivatives,including vertical farming,rooftop greenhouses and plant factories which are the extensions of CEA and have emerged as a response to the growing population,environmental degradation,and urbanization that are threatening food security.Finally,several opportunities and challenges have been identified in implementing the integrated CEA and vertical farming for urban agriculture.展开更多
Fermented foods represent an important segment of current food markets,especially traditional or ethnic food markets.The demand for efficient utilization of agrowastes,together with advancements in fermentation techno...Fermented foods represent an important segment of current food markets,especially traditional or ethnic food markets.The demand for efficient utilization of agrowastes,together with advancements in fermentation technologies(microbial-and enzyme-based processing),are stimulating rapid growth and innovation in the fermented food sector.In addition,the health-promoting benefits of fermented foods are attracting increasingly attention.The microorganisms contained in many common fermented foods can serve as“microfactories”to generate nutrients and bioactives with specific nutritional and health functionalities.Herein,recent research relating to the manufacture of fermented foods are critically reviewed,placing emphasis on the potential health benefits of fermentation-enabled wellness foods.The importance of the correct selection of microorganisms and raw materials and the need for precise control of fermentation processes are explored.Major knowledge gaps and obstacles to fermented food production and market penetration are discussed.The importance of integrating multidisciplinary knowledge,communicating with consumers,establishing regulatory frameworks specifically for fermentation-enabled wellness foods and functional fermented foods,are highlighted.展开更多
The rapid advancement of fundamental theories and computing capacity has brought artificial intelligence,internet of things, extended reality, and many other new intelligent technologies into our daily lives. Due to t...The rapid advancement of fundamental theories and computing capacity has brought artificial intelligence,internet of things, extended reality, and many other new intelligent technologies into our daily lives. Due to the lack of interpretability and reliability guarantees, it is extremely challenging to apply these technologies directly to real-world industrial systems. Here we present a new paradigm for establishing parallel factories in metaverses to accelerate the deployment of intelligent technologies in real-world industrial systems: QAII-1.0. Based on cyber-physical-social systems,QAII-1.0 incorporates complex social and human factors into the design and analysis of industrial operations and is capable of handling industrial operations involving complex social and human behaviors. In QAII-1.0, a field foundational model called Eu Artisan combined with scenarios engineering is developed to improve the intelligence of industrial systems while ensuring industrial interpretability and reliability. Finally, parallel oil fields in metaverses are established to demonstrate the operating procedure of QAII-1.0.展开更多
The article hypothesizes that DE and DM (UCM) are a “Form of Motion of a Special Nature”, where “Form of Motion” means “Eternal Motion” as the power of dynamics of different levels and varying degrees of self-su...The article hypothesizes that DE and DM (UCM) are a “Form of Motion of a Special Nature”, where “Form of Motion” means “Eternal Motion” as the power of dynamics of different levels and varying degrees of self-sufficiency, and by “Special Nature”, gravitational and two other properties of matter, “tied” to the “Eternal Movement” and completely dependent on it. Carriers of key properties of a “Special Nature” have been established: “0”-DE particles and “3”-DM particles (UDM). The unity of their inherent “motionally-gravitational” properties and the peculiarity of the relationship between “motion” and “gravity” are revealed: the higher the intensity of “Eternal Motion”, the stronger the gravitational properties of matter are manifested (and vice versa). The relationship of “time” with the “vibration frequency” and the “mass” of photons with the “degree of bonding and deformation properties of the field” is shown. The maximum level of gravity has been determined, which allows Nature to successfully create the Universe: such a landmark is the proximity to the property of the Primary Source—the “pure graviton” of the OSP space, the most powerful “motionally-gravitational” particle of the Universe. The reasons for the emergence of such an identity of the gravitational properties of particles with the indicators of a “pure graviton” are established: for “0”-DE particles, this is the acquisition of the function of “freedom of movement”;for “3”-DM particles (UDM), the creation of a special structure—a “double field” (“Main” and “Small”). The presence in the “double field” of specific “tools” for the creation of the worlds of the Universe—gravitational “waves” gives rise to impulses (shocks) of varying intensity and shape. A list of functions performed by “waves” in the “Main” and “Small” fields has been compiled. The specific conditions for the formation of “UDM Streams”, their transform展开更多
Objective:This study aimed to examine the causal model of eating behaviors among pregnant women working in industrial factories.Methods:This cross-sectional study was conducted on 210 participants,attending 4 healthca...Objective:This study aimed to examine the causal model of eating behaviors among pregnant women working in industrial factories.Methods:This cross-sectional study was conducted on 210 participants,attending 4 healthcare centers,at a tertiary care hospital in Chonburi province,Thailand.Data were collected using 7 questionnaires:demographic form,eating behavior questionnaire,perceived benefits of the healthy eating questionnaire,perceived barriers to the healthy eating questionnaire,perceived self-efficacy questionnaire,social support questionnaire,and accessibility to healthy foods questionnaire.Descriptive statistics and path analysis were used for data analysis.Results:The participants had relatively high mean scores for eating behaviors.The final model fitted well with the dataχ^(2)=12.86,df=10,P=0.23;χ^(2)/df=1.29;comparative fit index(CFI)=0.98;goodness-of-fit index(GFI)=0.98;adjusted goodness-of-fit index(AGFI)=0.95;root mean square error of approximation(RMSEA)=0.04.Four factors-perceived benefits(β=0.13,P<0.05),perceived self-efficacy in healthy eating(β=0.22,P<0.001),pregnancy planning(β=0.28,P<0.001),and accessibility to healthy foods in the factory(β=0.12,P<0.05)-positively affected eating behavior,while only perceived barriers to healthy eating had a negative effect on eating behavior(β=−0.24,P<0.001).All the above factors explained 27.2%of the variance in eating behaviors.Conclusions:Nurses or healthcare providers can apply these findings to create an eating behavior modification program,focusing on pregnancy planning,behavior-specific variables,and interpersonal and situational influence,to promote the nutritional status of pregnant women working in industrial factories.展开更多
Developing methylotrophic cell factories that can efficiently catalyze organic one-carbon(C1)feedstocks derived from electrocatalytic reduction of carbon dioxide into bio-based chemicals and biofuels is of strategic s...Developing methylotrophic cell factories that can efficiently catalyze organic one-carbon(C1)feedstocks derived from electrocatalytic reduction of carbon dioxide into bio-based chemicals and biofuels is of strategic significance for building a carbon-neutral,sustainable economic and industrial system.With the rapid advancement of RNA sequencing technology and mass spectrometer analysis,researchers have used these quantitative microbiology methods extensively,especially isotope-based metabolic flux analysis,to study the metabolic processes initiating from C1 feedstocks in natural C1-utilizing bacteria and synthetic C1 bacteria.This paper reviews the use of advanced quantitative analysis in recent years to understand the metabolic network and basic principles in the metabolism of natural C1-utilizing bacteria grown on methane,methanol,or formate.The acquired knowledge serves as a guide to rewire the central methylotrophic metabolism of natural C1-utilizing bacteria to improve the carbon conversion efficiency,and to engineer non-C1-utilizing bacteria into synthetic strains that can use C1 feedstocks as the sole carbon and energy source.These progresses ultimately enhance the design and construction of highly efficient C1-based cell factories to synthesize diverse high value-added products.The integration of quantitative biology and synthetic biology will advance the iterative cycle of understand–design–build–testing–learning to enhance C1-based biomanufacturing in the future.展开更多
Positive-sense RNA viruses modify intracellular calcium stores,endoplasmic reticulum and Golgi apparatus(Golgi)to generate membranous replication organelles known as viral factories.Viral factories provide a conducive...Positive-sense RNA viruses modify intracellular calcium stores,endoplasmic reticulum and Golgi apparatus(Golgi)to generate membranous replication organelles known as viral factories.Viral factories provide a conducive and substantial enclave for essential virus replication via concentrating necessary cellular factors and viral proteins in proximity.Here,we identified the vital role of a broadspectrum antiviral,peruvoside in limiting the formation of viral factories.Mechanistically,we revealed the pleiotropic cellular effect of Src and PLC kinase signaling via cyclin-dependent kinase 1 signaling leads to Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1(GBF1)phosphorylation and Golgi vesiculation by peruvoside treatment.The ramification of GBF1 phosphorylation fosters GBF1 deprivation consequentially activating downstream antiviral signaling by dampening viral factories formation.Further investigation showed signaling of ERK1/2 pathway via cyclin-dependent kinase 1 activation leading to GBF1 phosphorylation at Threonine 1337(T1337).We also showed 100%of protection in peruvoside-treated mouse model with a significant reduction in viral titre and without measurable cytotoxicity in serum.These findings highlight the importance of dissecting the broad-spectrum antiviral therapeutics mechanism and pave the way for consideration of peruvoside,host-directed antivirals for positive-sense RNA virus-mediated disease,in the interim where no vaccine is available.展开更多
Environmental sustainability is an increasingly important issue in industry.As an environmentally friendly and sustainable way,constructing microbial cell factories to produce all kinds of valuable products has attrac...Environmental sustainability is an increasingly important issue in industry.As an environmentally friendly and sustainable way,constructing microbial cell factories to produce all kinds of valuable products has attracted more and more attention.In the process of constructing microbial cell factories,systems biology plays a crucial role.This review summarizes the recent applications of systems biology in the design and construction of microbial cell factories from four perspectives,including functional genes/enzymes discovery,bottleneck pathways identification,strains tolerance improvement and design and construction of synthetic microbial consortia.Systems biology tools can be employed to identify functional genes/enzymes involved in the biosynthetic pathways of products.These discovered genes are introduced into appropriate chassis strains to build engineering microorganisms capable of producing products.Subsequently,systems biology tools are used to identify bottleneck pathways,improve strains tolerance and guide design and construction of synthetic microbial consortia,resulting in increasing the yield of engineered strains and constructing microbial cell factories successfully.展开更多
The global market demand for natural astaxanthin is rapidly increasing owing to its safety,the potential health benefits,and the diverse applications in food and pharmaceutical industries.The major native producers of...The global market demand for natural astaxanthin is rapidly increasing owing to its safety,the potential health benefits,and the diverse applications in food and pharmaceutical industries.The major native producers of natural astaxanthin on industrial scale are the alga Haematococcus pluvialis and the yeast Xanthopyllomyces dendrorhous.However,the natural production via these native producers is facing challenges of limited yield and high cost of cultivation and extraction.Alternatively,astaxanthin production via metabolically engineered non-native microbial cell factories such as Escherichia coli,Saccharomyces cerevisiae and Yarrowia lipolytica is another promising strategy to overcome these limitations.In this review we summarize the recent scientific and biotechnological progresses on astaxanthin biosynthetic pathways,transcriptional regulations,the interrelation with lipid metabolism,engineering strategies as well as fermentation process control in major native and non-native astaxanthin producers.These progresses illuminate the prospects of producing astaxanthin by microbial cell factories on industrial scale.展开更多
Cytochrome P450(CYP)enzymes play crucial roles during the evolution and diversification of ancestral monocel-lular eukaryotes into multicellular eukaryotic organisms due to their essential functionalities including ca...Cytochrome P450(CYP)enzymes play crucial roles during the evolution and diversification of ancestral monocel-lular eukaryotes into multicellular eukaryotic organisms due to their essential functionalities including catalysis of housekeeping biochemical reactions,synthesis of diverse metabolites,detoxification of xenobiotics,and con-tribution to environmental adaptation.Eukaryotic CYPs with versatile functionalities are undeniably regarded as promising biocatalysts with great potential for biotechnological,pharmaceutical and chemical industry applica-tions.Nevertheless,the modes of action and the challenges associated with these membrane-bound proteins have hampered the effective utilization of eukaryotic CYPs in a broader range.This review is focused on comprehen-sive and consolidated approaches to address the core challenges in heterologous expression of membrane-bound eukaryotic CYPs in different surrogate microbial cell factories,aiming to provide key insights for better studies and applications of diverse eukaryotic CYPs in the future.We also highlight the functional significance of the previously underrated cytochrome P450 reductases(CPRs)and provide a rational justification on the progression of CPR from auxiliary redox partner to function modulator in CYP catalysis.展开更多
Phloretin is an important skin-lightening and depigmenting agent from the peel of apples. Although de novo production of phloretin has been realized in microbes using the natural pathway from plants, the efficiency of...Phloretin is an important skin-lightening and depigmenting agent from the peel of apples. Although de novo production of phloretin has been realized in microbes using the natural pathway from plants, the efficiency of phloretin production is still not enough for industrial application. Here, we established an artificial pathway in the yeast to produce phloretin via assembling two genes of p-coumaroyl-CoA ligase(4CL) and chalcone synthase(CHS). CHS is a key enzyme which conventionally condenses a CoA-tethered starter with three molecules of malonyl-CoA to form the backbone of flavonoids. However, there was 33% of byproduct generated via CHS by condensing two molecules of malonyl-CoA during the fermentation process. Hence, we introduced a more efficient CHS and improved the supply of malonyl-CoA through two pathways;the by-product ratio was decreased from 33% to 17% and the production of phloretin was improved from 48 to 83.2 mg L^(-1). Finally, a fed-batch fermentation process was optimized and the production of phloretin reached 619.5 mg L^(-1), which was 14-fold higher than that of the previous studies. Our work established a platform for the biosynthesis of phloretin from the low-cost raw material 3-(4-hydroxyphenyl) propanoic acid and also illustrated the potential for industrial scale bio-manufacturing of phloretin.展开更多
In this paper we show that the MDA can be considered as a software industrialization pattern (or a software factory). Nearly all industries today are haunted with how to reduce costs, improve quality, faster time-to-m...In this paper we show that the MDA can be considered as a software industrialization pattern (or a software factory). Nearly all industries today are haunted with how to reduce costs, improve quality, faster time-to-market and to maximize profits. These challenges are particularly relevant to the software industry, because it still lags behind other technology sectors as regards industrialization and the timely delivery of software products. Most software are still of poor quality, always finished after deadlines (most don’t finish at all), and are very labour intensive. Here, we discuss the MDA as an approach that may help solving at the same time both problems of industrialization and ever-changing software infrastructures. We propose a MDA Engine based on a real case study in an IT services company. It is a proposal for a framework to create custom MDA tools, based on XMI, XSLT and the Visitor Pattern.展开更多
文摘Greenhouse cultivation has evolved from simple covered rows of open-fields crops to highly sophisticated controlled environment agriculture(CEA)facilities that projected the image of plant factories for urban agriculture.The advances and improvements in CEA have promoted the scientific solutions for the efficient production of plants in populated cities and multi-story buildings.Successful deployment of CEA for urban agriculture requires many components and subsystems,as well as the understanding of the external influencing factors that should be systematically considered and integrated.This review is an attempt to highlight some of the most recent advances in greenhouse technology and CEA in order to raise the awareness for technology transfer and adaptation,which is necessary for a successful transition to urban agriculture.This study reviewed several aspects of a high-tech CEA system including improvements in the frame and covering materials,environment perception and data sharing,and advanced microclimate control and energy optimization models.This research highlighted urban agriculture and its derivatives,including vertical farming,rooftop greenhouses and plant factories which are the extensions of CEA and have emerged as a response to the growing population,environmental degradation,and urbanization that are threatening food security.Finally,several opportunities and challenges have been identified in implementing the integrated CEA and vertical farming for urban agriculture.
文摘Fermented foods represent an important segment of current food markets,especially traditional or ethnic food markets.The demand for efficient utilization of agrowastes,together with advancements in fermentation technologies(microbial-and enzyme-based processing),are stimulating rapid growth and innovation in the fermented food sector.In addition,the health-promoting benefits of fermented foods are attracting increasingly attention.The microorganisms contained in many common fermented foods can serve as“microfactories”to generate nutrients and bioactives with specific nutritional and health functionalities.Herein,recent research relating to the manufacture of fermented foods are critically reviewed,placing emphasis on the potential health benefits of fermentation-enabled wellness foods.The importance of the correct selection of microorganisms and raw materials and the need for precise control of fermentation processes are explored.Major knowledge gaps and obstacles to fermented food production and market penetration are discussed.The importance of integrating multidisciplinary knowledge,communicating with consumers,establishing regulatory frameworks specifically for fermentation-enabled wellness foods and functional fermented foods,are highlighted.
基金supported in part by the National Natural Science Foundation of China(1811463,62073321)Modeling,Decision and Control Algorithms for Servo Drive Systems。
文摘The rapid advancement of fundamental theories and computing capacity has brought artificial intelligence,internet of things, extended reality, and many other new intelligent technologies into our daily lives. Due to the lack of interpretability and reliability guarantees, it is extremely challenging to apply these technologies directly to real-world industrial systems. Here we present a new paradigm for establishing parallel factories in metaverses to accelerate the deployment of intelligent technologies in real-world industrial systems: QAII-1.0. Based on cyber-physical-social systems,QAII-1.0 incorporates complex social and human factors into the design and analysis of industrial operations and is capable of handling industrial operations involving complex social and human behaviors. In QAII-1.0, a field foundational model called Eu Artisan combined with scenarios engineering is developed to improve the intelligence of industrial systems while ensuring industrial interpretability and reliability. Finally, parallel oil fields in metaverses are established to demonstrate the operating procedure of QAII-1.0.
文摘The article hypothesizes that DE and DM (UCM) are a “Form of Motion of a Special Nature”, where “Form of Motion” means “Eternal Motion” as the power of dynamics of different levels and varying degrees of self-sufficiency, and by “Special Nature”, gravitational and two other properties of matter, “tied” to the “Eternal Movement” and completely dependent on it. Carriers of key properties of a “Special Nature” have been established: “0”-DE particles and “3”-DM particles (UDM). The unity of their inherent “motionally-gravitational” properties and the peculiarity of the relationship between “motion” and “gravity” are revealed: the higher the intensity of “Eternal Motion”, the stronger the gravitational properties of matter are manifested (and vice versa). The relationship of “time” with the “vibration frequency” and the “mass” of photons with the “degree of bonding and deformation properties of the field” is shown. The maximum level of gravity has been determined, which allows Nature to successfully create the Universe: such a landmark is the proximity to the property of the Primary Source—the “pure graviton” of the OSP space, the most powerful “motionally-gravitational” particle of the Universe. The reasons for the emergence of such an identity of the gravitational properties of particles with the indicators of a “pure graviton” are established: for “0”-DE particles, this is the acquisition of the function of “freedom of movement”;for “3”-DM particles (UDM), the creation of a special structure—a “double field” (“Main” and “Small”). The presence in the “double field” of specific “tools” for the creation of the worlds of the Universe—gravitational “waves” gives rise to impulses (shocks) of varying intensity and shape. A list of functions performed by “waves” in the “Main” and “Small” fields has been compiled. The specific conditions for the formation of “UDM Streams”, their transform
文摘Objective:This study aimed to examine the causal model of eating behaviors among pregnant women working in industrial factories.Methods:This cross-sectional study was conducted on 210 participants,attending 4 healthcare centers,at a tertiary care hospital in Chonburi province,Thailand.Data were collected using 7 questionnaires:demographic form,eating behavior questionnaire,perceived benefits of the healthy eating questionnaire,perceived barriers to the healthy eating questionnaire,perceived self-efficacy questionnaire,social support questionnaire,and accessibility to healthy foods questionnaire.Descriptive statistics and path analysis were used for data analysis.Results:The participants had relatively high mean scores for eating behaviors.The final model fitted well with the dataχ^(2)=12.86,df=10,P=0.23;χ^(2)/df=1.29;comparative fit index(CFI)=0.98;goodness-of-fit index(GFI)=0.98;adjusted goodness-of-fit index(AGFI)=0.95;root mean square error of approximation(RMSEA)=0.04.Four factors-perceived benefits(β=0.13,P<0.05),perceived self-efficacy in healthy eating(β=0.22,P<0.001),pregnancy planning(β=0.28,P<0.001),and accessibility to healthy foods in the factory(β=0.12,P<0.05)-positively affected eating behavior,while only perceived barriers to healthy eating had a negative effect on eating behavior(β=−0.24,P<0.001).All the above factors explained 27.2%of the variance in eating behaviors.Conclusions:Nurses or healthcare providers can apply these findings to create an eating behavior modification program,focusing on pregnancy planning,behavior-specific variables,and interpersonal and situational influence,to promote the nutritional status of pregnant women working in industrial factories.
基金National Key R&D Program of China,Grant Award Numbers:2018YFA0901500,2021YFC2103500National Natural Science Foundation of China,Grant/Award Numbers:22078169,32000003,31900004。
文摘Developing methylotrophic cell factories that can efficiently catalyze organic one-carbon(C1)feedstocks derived from electrocatalytic reduction of carbon dioxide into bio-based chemicals and biofuels is of strategic significance for building a carbon-neutral,sustainable economic and industrial system.With the rapid advancement of RNA sequencing technology and mass spectrometer analysis,researchers have used these quantitative microbiology methods extensively,especially isotope-based metabolic flux analysis,to study the metabolic processes initiating from C1 feedstocks in natural C1-utilizing bacteria and synthetic C1 bacteria.This paper reviews the use of advanced quantitative analysis in recent years to understand the metabolic network and basic principles in the metabolism of natural C1-utilizing bacteria grown on methane,methanol,or formate.The acquired knowledge serves as a guide to rewire the central methylotrophic metabolism of natural C1-utilizing bacteria to improve the carbon conversion efficiency,and to engineer non-C1-utilizing bacteria into synthetic strains that can use C1 feedstocks as the sole carbon and energy source.These progresses ultimately enhance the design and construction of highly efficient C1-based cell factories to synthesize diverse high value-added products.The integration of quantitative biology and synthetic biology will advance the iterative cycle of understand–design–build–testing–learning to enhance C1-based biomanufacturing in the future.
基金Ministry of Education Tier 2 grant(MOE2017-T2-1-078 and MOE-2017-T2-2-014,Singapore)National Research Foundation Competitive Research Programme(NRF-CRP21-2018-0004,Singapore)。
文摘Positive-sense RNA viruses modify intracellular calcium stores,endoplasmic reticulum and Golgi apparatus(Golgi)to generate membranous replication organelles known as viral factories.Viral factories provide a conducive and substantial enclave for essential virus replication via concentrating necessary cellular factors and viral proteins in proximity.Here,we identified the vital role of a broadspectrum antiviral,peruvoside in limiting the formation of viral factories.Mechanistically,we revealed the pleiotropic cellular effect of Src and PLC kinase signaling via cyclin-dependent kinase 1 signaling leads to Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1(GBF1)phosphorylation and Golgi vesiculation by peruvoside treatment.The ramification of GBF1 phosphorylation fosters GBF1 deprivation consequentially activating downstream antiviral signaling by dampening viral factories formation.Further investigation showed signaling of ERK1/2 pathway via cyclin-dependent kinase 1 activation leading to GBF1 phosphorylation at Threonine 1337(T1337).We also showed 100%of protection in peruvoside-treated mouse model with a significant reduction in viral titre and without measurable cytotoxicity in serum.These findings highlight the importance of dissecting the broad-spectrum antiviral therapeutics mechanism and pave the way for consideration of peruvoside,host-directed antivirals for positive-sense RNA virus-mediated disease,in the interim where no vaccine is available.
基金by the National Key Research and Development Program of China (2019YFA0706900)National Natural Science Foundation of China (22278310).
文摘Environmental sustainability is an increasingly important issue in industry.As an environmentally friendly and sustainable way,constructing microbial cell factories to produce all kinds of valuable products has attracted more and more attention.In the process of constructing microbial cell factories,systems biology plays a crucial role.This review summarizes the recent applications of systems biology in the design and construction of microbial cell factories from four perspectives,including functional genes/enzymes discovery,bottleneck pathways identification,strains tolerance improvement and design and construction of synthetic microbial consortia.Systems biology tools can be employed to identify functional genes/enzymes involved in the biosynthetic pathways of products.These discovered genes are introduced into appropriate chassis strains to build engineering microorganisms capable of producing products.Subsequently,systems biology tools are used to identify bottleneck pathways,improve strains tolerance and guide design and construction of synthetic microbial consortia,resulting in increasing the yield of engineered strains and constructing microbial cell factories successfully.
基金We gratefully acknowledge the financial support from the National Key Research and Development Program of China(2020YFA0907800)Shandong Jincheng Bio-Pharmaceutical Co.,Ltd.
文摘The global market demand for natural astaxanthin is rapidly increasing owing to its safety,the potential health benefits,and the diverse applications in food and pharmaceutical industries.The major native producers of natural astaxanthin on industrial scale are the alga Haematococcus pluvialis and the yeast Xanthopyllomyces dendrorhous.However,the natural production via these native producers is facing challenges of limited yield and high cost of cultivation and extraction.Alternatively,astaxanthin production via metabolically engineered non-native microbial cell factories such as Escherichia coli,Saccharomyces cerevisiae and Yarrowia lipolytica is another promising strategy to overcome these limitations.In this review we summarize the recent scientific and biotechnological progresses on astaxanthin biosynthetic pathways,transcriptional regulations,the interrelation with lipid metabolism,engineering strategies as well as fermentation process control in major native and non-native astaxanthin producers.These progresses illuminate the prospects of producing astaxanthin by microbial cell factories on industrial scale.
基金supported by the National Key Research and Develop-ment Program of China(2019YFA0706900)the National Natural Sci-ence Foundation of China(32025001 and 21472204)the Shandong Provincial Natural Science Foundation(ZR2019ZD20).
文摘Cytochrome P450(CYP)enzymes play crucial roles during the evolution and diversification of ancestral monocel-lular eukaryotes into multicellular eukaryotic organisms due to their essential functionalities including catalysis of housekeeping biochemical reactions,synthesis of diverse metabolites,detoxification of xenobiotics,and con-tribution to environmental adaptation.Eukaryotic CYPs with versatile functionalities are undeniably regarded as promising biocatalysts with great potential for biotechnological,pharmaceutical and chemical industry applica-tions.Nevertheless,the modes of action and the challenges associated with these membrane-bound proteins have hampered the effective utilization of eukaryotic CYPs in a broader range.This review is focused on comprehen-sive and consolidated approaches to address the core challenges in heterologous expression of membrane-bound eukaryotic CYPs in different surrogate microbial cell factories,aiming to provide key insights for better studies and applications of diverse eukaryotic CYPs in the future.We also highlight the functional significance of the previously underrated cytochrome P450 reductases(CPRs)and provide a rational justification on the progression of CPR from auxiliary redox partner to function modulator in CYP catalysis.
基金financially supported by Talents Team Construction Fund of Northwestern Polytechnical University (NWPU)the National Natural Science Foundation of China (31701722)+1 种基金the China Postdoctoral Science Foundation (2017M620471)the National Natural Science Foundation of China (31901026)。
文摘Phloretin is an important skin-lightening and depigmenting agent from the peel of apples. Although de novo production of phloretin has been realized in microbes using the natural pathway from plants, the efficiency of phloretin production is still not enough for industrial application. Here, we established an artificial pathway in the yeast to produce phloretin via assembling two genes of p-coumaroyl-CoA ligase(4CL) and chalcone synthase(CHS). CHS is a key enzyme which conventionally condenses a CoA-tethered starter with three molecules of malonyl-CoA to form the backbone of flavonoids. However, there was 33% of byproduct generated via CHS by condensing two molecules of malonyl-CoA during the fermentation process. Hence, we introduced a more efficient CHS and improved the supply of malonyl-CoA through two pathways;the by-product ratio was decreased from 33% to 17% and the production of phloretin was improved from 48 to 83.2 mg L^(-1). Finally, a fed-batch fermentation process was optimized and the production of phloretin reached 619.5 mg L^(-1), which was 14-fold higher than that of the previous studies. Our work established a platform for the biosynthesis of phloretin from the low-cost raw material 3-(4-hydroxyphenyl) propanoic acid and also illustrated the potential for industrial scale bio-manufacturing of phloretin.
文摘In this paper we show that the MDA can be considered as a software industrialization pattern (or a software factory). Nearly all industries today are haunted with how to reduce costs, improve quality, faster time-to-market and to maximize profits. These challenges are particularly relevant to the software industry, because it still lags behind other technology sectors as regards industrialization and the timely delivery of software products. Most software are still of poor quality, always finished after deadlines (most don’t finish at all), and are very labour intensive. Here, we discuss the MDA as an approach that may help solving at the same time both problems of industrialization and ever-changing software infrastructures. We propose a MDA Engine based on a real case study in an IT services company. It is a proposal for a framework to create custom MDA tools, based on XMI, XSLT and the Visitor Pattern.
