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
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.
