Terpenoids play important roles in productivity and product quality in tea(Camellia sinensis),not only because volatile terpenoids contribute significantly to the aroma of teas,but terpenoid-derived light harvesting p...Terpenoids play important roles in productivity and product quality in tea(Camellia sinensis),not only because volatile terpenoids contribute significantly to the aroma of teas,but terpenoid-derived light harvesting pigments and phytohormones such as strigolactones implement photosynthesis and branching in plants.All terpenoids are derived from isopentenyl diphosphate(IPP),dimethylallyl diphosphate(DMAPP) produced by methyl-erythritol-phosphate(MEP) and mevalonate(MVA) pathways,the early steps of isoprenoid biosynthesis.For the purpose to determine key genes in the MEP and MVA pathways in C.sinensis,five genes with complete coding sequence and three with partial sequence were obtained based on previously attained transcriptome data and polymerase chain reaction approach in this study.In silico analyses suggested that the five genes with full coding sequence individually encoded acetyl-CoA C-acetyltransferase(CsAACT),3-hydroxy-3-methylglutaryl-CoA synthase(CsHMGS),4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol kinase(CsCMK),1-hydroxy-2-methyl-2-(E)-butenyl-4-diphosphate synthase(CsHDS),and farnesyl pyrophosphate synthase(CsFPS).Additionally,studies on metabolite-mediated gene expression were performed using tea cell suspensions and leaf-disc cultures.Our data showed that the addition of acetyl-CoA increased the transcript level of CsAACT and CsHMGS by 1.5- and 3-fold,respectively.The addition of deoxy-D-xylulose 5-phosphate(DXP) induced the expression of CsCMK and CsHDS by 2.3- and 1.5-fold,respectively.The CsFPS expression was approximately 2-fold higher when treated with DXP,IPP or DMAPP than the untreated control,but this induction was not observed with the acetyl-CoA treatment.Our studies indicated that expression of CsAACT,CsHMGS,CsCMK,CsHDS,and CsFPS were metabolite-mediated in a different extent.展开更多
Stilbenes are natural phenolic compounds which function as antimicrobial phytoalexins in plants and affect human health as cardioprotective, antibaceteria, antioxidative and antineoplastic agents. In this review, the ...Stilbenes are natural phenolic compounds which function as antimicrobial phytoalexins in plants and affect human health as cardioprotective, antibaceteria, antioxidative and antineoplastic agents. In this review, the progresses of study on relevant enzymes, genes, and regulation mechanism in biosynthesis pathway of stilbenes are described. Here we introduce a holistic and systematic method of researching relevant enzymes, genes and other regulatory factors in biosynthesis pathway of stilbenes—Systems biology. The application of knowledge of relative enzymes, genes and regulation mechanisms in stilbenes biosynthesis in metabolic engineering which is used as a tool of improving the disease resistance of plants and health caring quality of crops is also discussed.展开更多
Cotton(Gossypium hirsutum L.) is the leading fiber crop and one of the mainstays of the economy in the world.Cotton fibers,as the main product of cotton plants,are unicellular,linear
Computational systems biology approaches provide insights to understand complex molecular phenomena in living systems. Such understanding demands the need to systematically interrogate and review existing literature t...Computational systems biology approaches provide insights to understand complex molecular phenomena in living systems. Such understanding demands the need to systematically interrogate and review existing literature to refine and distil key molecular pathways. This paper explores a methodological process to identify key molecular pathways from systematic bioinformatics literature review. This process is used to identify molecular pathways for a ubiquitous molecular process in all plant biological systems: C1 metabolism and formaldehyde detoxification, specific to maize. The C1 metabolism is essential for all organisms to provide one-carbon units for methylation and other types of modifications, as well as for nucleic acid, amino acid, and other biomolecule syntheses. Formaldehyde is a toxic one-carbon molecule which is produced endogenously and found in the environment, and whose detoxification is an important part of C1 metabolism. This systematic review involves a five-part process: 1) framing of the research question;2) literature collection based on a parallel search strategy;3) relevant study selection based on search refinement;4) molecular pathway identification;and 5) integration of key molecular pathway mechanisms to yield a well-defined set molecular systems associated with a particular biochemical function. Findings from this systematic review produced three main molecular systems: a) methionine biosynthesis;b) the methylation cycle;and c) formaldehyde detoxification. Specific insights from the resulting molecular pathways indicate that normal C1 metabolism involves the transfer of a carbon group from serine through a folate-mediated pathway to methionine, and eventually the methylation of a biomolecule. In photosynthetic tissues, C1 metabolism often proceeds in reverse towards serine biosynthesis and formate oxidation. C1 metabolism, in maize, appears to be present in the developing embryo and endosperm indicating that these cells are vulnerable to perturbations in formaldehyde detoxification. These insights demonstrate the value of a systematic bioinformatics literature review process from a broad spectrum of domain literature to specific and relevant molecular pathways.展开更多
Korla fragrant pear(KFP)with special fragrance is a unique cultivar in Xinjiang,China.In order to explore the biosynthesis molecular mechanism of chlorogenic acid(CGA)in KFP,the samples at different development period...Korla fragrant pear(KFP)with special fragrance is a unique cultivar in Xinjiang,China.In order to explore the biosynthesis molecular mechanism of chlorogenic acid(CGA)in KFP,the samples at different development periods were collected for transcriptome analysis.High performance liquid chromatography analysis showed that CGA contents of KFP at 88,118 and 163 days after full bloom were(20.96±1.84),(12.01±0.91)and(7.16±0.41)mg/100 g,respectively,and decreased with the fruit development.Pears from these typical 3 periods were selected for de novo transcriptome assemble and 68059 unigenes were assembled from 444037960 clean reads.One‘phenylpropanoid biosynthesis’pathway including 57 unigenes,11 PALs,1 PTAL,64CLs,9 C4Hs,25 HCTs and 5 C3’Hs related to CGA biosynthesis was determined.It was found that the expression levels of 11 differentially expressed genes including 1 PAL,2 C4Hs,34CLs and 5 HCTs were consistent with the change of CGA content.Quantitative polymerase chain reaction analysis further showed that 8 unigenes involved in CGA biosynthesis were consistent with the RNA-seq data.These findings will provide a comprehensive understanding and valuable information on the genetic engineering and molecular breeding in KFP.展开更多
Nutrigenomic studies were conducted to uncover the mechanism of action for the hypoglycemic and insulin sensitizing effects of UP780. From high fat diet-induced obesity mouse model for UP780, livers and white adipose ...Nutrigenomic studies were conducted to uncover the mechanism of action for the hypoglycemic and insulin sensitizing effects of UP780. From high fat diet-induced obesity mouse model for UP780, livers and white adipose tissues (WAT) from groups of lean control, high fat diet (HFD), and HFD treated with UP780 were collected for microarray study. Microarray generated gene expression changes were applied to Ingenuity Pathway Analysis for changes in canonical metabolic and signaling pathways. Microarray was validated by quantitative reverse transcriptase-polymerase chain reaction (QPCR), Western blots, liver triglyceride, liver cholesterol, liver steatosis, and insulin ELISA. UP780 treatment decreased liver gene expressions for multiple enzymes involved in fatty acid biosynthesis and triglyceride production. UP780 treatment increased gene expressions globally for the insulin receptor signaling pathway in WAT. Both liver triglyceride and liver cholesterol levels were significantly reduced by UP780 over HFD. The reduction of liver fat was confirmed by microscopic analysis of liver steatosis. Finally, UP780 significantly decreased fasting plasma insulin level over HFD. The mechanism of action for UP780 indicated a reduction of liver fat accumulation and an enhancement in adipose tissue insulin signaling pathway. This provided mechanistic explanation for the in vivo UP780 effects of enhanced insulin sensitiveity and decreased blood glucose in mouse diabetes and prediabetes models.展开更多
2-Oxoglutarate(2OG)-dependent dioxygenases(2-ODDs)are omnipresent iron-containing non-heme enzymes that catalyze various oxidation-reduction reactions in plant growth and development,nucleic acid modification and seco...2-Oxoglutarate(2OG)-dependent dioxygenases(2-ODDs)are omnipresent iron-containing non-heme enzymes that catalyze various oxidation-reduction reactions in plant growth and development,nucleic acid modification and secondary metabolism.We systematically summarized recent research on the oxidative modifications of plant 2-ODDs and related enzymes,their vital importance in the biosynthesis of plant special metabolites,and their catalytic specificity/flexibility,and discussed the potential of 2-ODD as a new approach for the identification of pivotal genes and the elucidation of biosynthetic pathway.展开更多
Terpenoids constitute the largest class of natural products with complex structures,essential functions,and versatile applications.Creation of new building blocks beyond the conventional five-carbon(C_(5))units,dimeth...Terpenoids constitute the largest class of natural products with complex structures,essential functions,and versatile applications.Creation of new building blocks beyond the conventional five-carbon(C_(5))units,dimethylallyl diphosphate(DMAPP)and isopentenyl diphosphate,expands significantly the chemical space of terpenoids.Structure-guided engineering of an S-adenosylmethionine-dependent geranyl diphosphate(GPP)C2-methyltransferase from Streptomyces coelicolor yielded variants converting DMAPP to a new C_(6) unit,2-methyl-DMAPP.Mutation of the Gly residue at the position 202 resulted in a smaller substrate-binding pocket to fit DMAPP instead of its native substrate GPP.Replacement of Phe residue at the position 222 with a Tyr residue contributed to DMAPP binding via hydrogen bond.Furthermore,using Escherichia coli as the chassis,we demonstrated that 2-methyl-DMAPP was accepted as a start unit to generate noncanonical trans-and cis-prenyl diphosphates(C_(5n+1))and terpenoids.This work provides insights into substrate recognition of prenyl diphosphate methyltransferases,and strategies to diversify terpenoids by expanding the building block portfolio.展开更多
Terpenoids are a diverse class of natural products widely used as pharmaceuticals,perfumes,flavors,and biofuels.Traditionally,terpenoids are obtained from natural sources,such as plants,but their production is limited...Terpenoids are a diverse class of natural products widely used as pharmaceuticals,perfumes,flavors,and biofuels.Traditionally,terpenoids are obtained from natural sources,such as plants,but their production is limited by the insufficiency of resources and low yields of extraction.Microbial production of terpenoids has emerged as a promising alternative due to that it is sustainable and easy to scale up.This review aims to summarize recent advances in microbial production of terpenoids from inexpensive biomass-derived feedstocks.Metabolic pathways and key enzymes involved in terpenoid biosynthesis are introduced.Microorganisms that can utilize low-cost lignocellulosic feedstocks for terpenoid production are highlighted.The challenges and prospects faced by microbial terpenoid production are proposed.We believe that continuous progress in the fields of biomass transformation and synthetic biology will ultimately achieve industrial production of microbial terpenoids.展开更多
基金funded by the National Science Foundation in China (#31070614 to S.Wei)Fund for the Doctoral Program of Higher Education of The ministry of Education(#20123418110002,to S.Wei)+1 种基金the Program for Changjiang Scholars and Innovative Research Team in Universities (IRT1101 to Z.Z.Zhang)the "Twelfth Five-Year" National Key Basic Research and Development Project (973) in China (2012CB722903 to Xiao-Chun Wan)
文摘Terpenoids play important roles in productivity and product quality in tea(Camellia sinensis),not only because volatile terpenoids contribute significantly to the aroma of teas,but terpenoid-derived light harvesting pigments and phytohormones such as strigolactones implement photosynthesis and branching in plants.All terpenoids are derived from isopentenyl diphosphate(IPP),dimethylallyl diphosphate(DMAPP) produced by methyl-erythritol-phosphate(MEP) and mevalonate(MVA) pathways,the early steps of isoprenoid biosynthesis.For the purpose to determine key genes in the MEP and MVA pathways in C.sinensis,five genes with complete coding sequence and three with partial sequence were obtained based on previously attained transcriptome data and polymerase chain reaction approach in this study.In silico analyses suggested that the five genes with full coding sequence individually encoded acetyl-CoA C-acetyltransferase(CsAACT),3-hydroxy-3-methylglutaryl-CoA synthase(CsHMGS),4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol kinase(CsCMK),1-hydroxy-2-methyl-2-(E)-butenyl-4-diphosphate synthase(CsHDS),and farnesyl pyrophosphate synthase(CsFPS).Additionally,studies on metabolite-mediated gene expression were performed using tea cell suspensions and leaf-disc cultures.Our data showed that the addition of acetyl-CoA increased the transcript level of CsAACT and CsHMGS by 1.5- and 3-fold,respectively.The addition of deoxy-D-xylulose 5-phosphate(DXP) induced the expression of CsCMK and CsHDS by 2.3- and 1.5-fold,respectively.The CsFPS expression was approximately 2-fold higher when treated with DXP,IPP or DMAPP than the untreated control,but this induction was not observed with the acetyl-CoA treatment.Our studies indicated that expression of CsAACT,CsHMGS,CsCMK,CsHDS,and CsFPS were metabolite-mediated in a different extent.
文摘Stilbenes are natural phenolic compounds which function as antimicrobial phytoalexins in plants and affect human health as cardioprotective, antibaceteria, antioxidative and antineoplastic agents. In this review, the progresses of study on relevant enzymes, genes, and regulation mechanism in biosynthesis pathway of stilbenes are described. Here we introduce a holistic and systematic method of researching relevant enzymes, genes and other regulatory factors in biosynthesis pathway of stilbenes—Systems biology. The application of knowledge of relative enzymes, genes and regulation mechanisms in stilbenes biosynthesis in metabolic engineering which is used as a tool of improving the disease resistance of plants and health caring quality of crops is also discussed.
基金This work was supported by the National Natural Science Foundation of China (No 30370904and No 30671258)the National High Technology Research and Development Program(863 project)of China (No 2006AA10Z121)the Program for New Century Excellent Talents in University(No NCET-07-0712)
文摘Cotton(Gossypium hirsutum L.) is the leading fiber crop and one of the mainstays of the economy in the world.Cotton fibers,as the main product of cotton plants,are unicellular,linear
文摘Computational systems biology approaches provide insights to understand complex molecular phenomena in living systems. Such understanding demands the need to systematically interrogate and review existing literature to refine and distil key molecular pathways. This paper explores a methodological process to identify key molecular pathways from systematic bioinformatics literature review. This process is used to identify molecular pathways for a ubiquitous molecular process in all plant biological systems: C1 metabolism and formaldehyde detoxification, specific to maize. The C1 metabolism is essential for all organisms to provide one-carbon units for methylation and other types of modifications, as well as for nucleic acid, amino acid, and other biomolecule syntheses. Formaldehyde is a toxic one-carbon molecule which is produced endogenously and found in the environment, and whose detoxification is an important part of C1 metabolism. This systematic review involves a five-part process: 1) framing of the research question;2) literature collection based on a parallel search strategy;3) relevant study selection based on search refinement;4) molecular pathway identification;and 5) integration of key molecular pathway mechanisms to yield a well-defined set molecular systems associated with a particular biochemical function. Findings from this systematic review produced three main molecular systems: a) methionine biosynthesis;b) the methylation cycle;and c) formaldehyde detoxification. Specific insights from the resulting molecular pathways indicate that normal C1 metabolism involves the transfer of a carbon group from serine through a folate-mediated pathway to methionine, and eventually the methylation of a biomolecule. In photosynthetic tissues, C1 metabolism often proceeds in reverse towards serine biosynthesis and formate oxidation. C1 metabolism, in maize, appears to be present in the developing embryo and endosperm indicating that these cells are vulnerable to perturbations in formaldehyde detoxification. These insights demonstrate the value of a systematic bioinformatics literature review process from a broad spectrum of domain literature to specific and relevant molecular pathways.
基金supported by Major scientific and technological projects of XPCC(2020KWZ-012)。
文摘Korla fragrant pear(KFP)with special fragrance is a unique cultivar in Xinjiang,China.In order to explore the biosynthesis molecular mechanism of chlorogenic acid(CGA)in KFP,the samples at different development periods were collected for transcriptome analysis.High performance liquid chromatography analysis showed that CGA contents of KFP at 88,118 and 163 days after full bloom were(20.96±1.84),(12.01±0.91)and(7.16±0.41)mg/100 g,respectively,and decreased with the fruit development.Pears from these typical 3 periods were selected for de novo transcriptome assemble and 68059 unigenes were assembled from 444037960 clean reads.One‘phenylpropanoid biosynthesis’pathway including 57 unigenes,11 PALs,1 PTAL,64CLs,9 C4Hs,25 HCTs and 5 C3’Hs related to CGA biosynthesis was determined.It was found that the expression levels of 11 differentially expressed genes including 1 PAL,2 C4Hs,34CLs and 5 HCTs were consistent with the change of CGA content.Quantitative polymerase chain reaction analysis further showed that 8 unigenes involved in CGA biosynthesis were consistent with the RNA-seq data.These findings will provide a comprehensive understanding and valuable information on the genetic engineering and molecular breeding in KFP.
文摘Nutrigenomic studies were conducted to uncover the mechanism of action for the hypoglycemic and insulin sensitizing effects of UP780. From high fat diet-induced obesity mouse model for UP780, livers and white adipose tissues (WAT) from groups of lean control, high fat diet (HFD), and HFD treated with UP780 were collected for microarray study. Microarray generated gene expression changes were applied to Ingenuity Pathway Analysis for changes in canonical metabolic and signaling pathways. Microarray was validated by quantitative reverse transcriptase-polymerase chain reaction (QPCR), Western blots, liver triglyceride, liver cholesterol, liver steatosis, and insulin ELISA. UP780 treatment decreased liver gene expressions for multiple enzymes involved in fatty acid biosynthesis and triglyceride production. UP780 treatment increased gene expressions globally for the insulin receptor signaling pathway in WAT. Both liver triglyceride and liver cholesterol levels were significantly reduced by UP780 over HFD. The reduction of liver fat was confirmed by microscopic analysis of liver steatosis. Finally, UP780 significantly decreased fasting plasma insulin level over HFD. The mechanism of action for UP780 indicated a reduction of liver fat accumulation and an enhancement in adipose tissue insulin signaling pathway. This provided mechanistic explanation for the in vivo UP780 effects of enhanced insulin sensitiveity and decreased blood glucose in mouse diabetes and prediabetes models.
基金This work was supported by the National Natural Science Foundation of China (81373890) the Research Fund for the Doctoral Program of Higher Education (20121210110011), and the Natural Science Foundation of Tianjin (No. 12JCZDJC26100).
基金This work was supported by the National Key R&D Program of China(2020YFA0908000)the National Natural Science Foundation of China(81773830)+1 种基金the Key Project at central government level:The ability establishment of sustainable use for valuable Chinese medicine resources(2060302-1806-03)National Program for Special Support of Eminent Professionals.
文摘2-Oxoglutarate(2OG)-dependent dioxygenases(2-ODDs)are omnipresent iron-containing non-heme enzymes that catalyze various oxidation-reduction reactions in plant growth and development,nucleic acid modification and secondary metabolism.We systematically summarized recent research on the oxidative modifications of plant 2-ODDs and related enzymes,their vital importance in the biosynthesis of plant special metabolites,and their catalytic specificity/flexibility,and discussed the potential of 2-ODD as a new approach for the identification of pivotal genes and the elucidation of biosynthetic pathway.
基金supported in part by the National Key R&D Program of China (2021YFA0909600 and 2019YFA0909400).
文摘Terpenoids constitute the largest class of natural products with complex structures,essential functions,and versatile applications.Creation of new building blocks beyond the conventional five-carbon(C_(5))units,dimethylallyl diphosphate(DMAPP)and isopentenyl diphosphate,expands significantly the chemical space of terpenoids.Structure-guided engineering of an S-adenosylmethionine-dependent geranyl diphosphate(GPP)C2-methyltransferase from Streptomyces coelicolor yielded variants converting DMAPP to a new C_(6) unit,2-methyl-DMAPP.Mutation of the Gly residue at the position 202 resulted in a smaller substrate-binding pocket to fit DMAPP instead of its native substrate GPP.Replacement of Phe residue at the position 222 with a Tyr residue contributed to DMAPP binding via hydrogen bond.Furthermore,using Escherichia coli as the chassis,we demonstrated that 2-methyl-DMAPP was accepted as a start unit to generate noncanonical trans-and cis-prenyl diphosphates(C_(5n+1))and terpenoids.This work provides insights into substrate recognition of prenyl diphosphate methyltransferases,and strategies to diversify terpenoids by expanding the building block portfolio.
基金the National Key Research and Development Program of China(No.2022YFC2104700).
文摘Terpenoids are a diverse class of natural products widely used as pharmaceuticals,perfumes,flavors,and biofuels.Traditionally,terpenoids are obtained from natural sources,such as plants,but their production is limited by the insufficiency of resources and low yields of extraction.Microbial production of terpenoids has emerged as a promising alternative due to that it is sustainable and easy to scale up.This review aims to summarize recent advances in microbial production of terpenoids from inexpensive biomass-derived feedstocks.Metabolic pathways and key enzymes involved in terpenoid biosynthesis are introduced.Microorganisms that can utilize low-cost lignocellulosic feedstocks for terpenoid production are highlighted.The challenges and prospects faced by microbial terpenoid production are proposed.We believe that continuous progress in the fields of biomass transformation and synthetic biology will ultimately achieve industrial production of microbial terpenoids.