Adult BALB/c mice, individually housed, were stimulated with nine different stressors, arranged randomly, for 4 continuous weeks to generate an animal model of chronic stress. In chronically stressed mice, spontaneous...Adult BALB/c mice, individually housed, were stimulated with nine different stressors, arranged randomly, for 4 continuous weeks to generate an animal model of chronic stress. In chronically stressed mice, spontaneous locomotor activity was significantly decreased, escape latency in the Morris water maze test was prolonged, serum levels of total thyrotropin and total triiodothyronine were significantly decreased, and dopamine and norepinephrine content in the pallium, hippocampus and hypothalamus were significantly reduced. All of these changes were suppressed, to varying degrees, by L-tyrosine supplementation. These findings indicate that the neuroendocrine network plays an important role in chronic stress, and that L-tyrosine supplementation has therapeutic effects.展开更多
For the efficient conversion of L-tyrosine(L-Tyr)to tyrosol,which is an aromatic compound widely used in the pharmaceutical and chemical industries,a novel four-enzyme cascade pathway based on the Ehrlich pathway of S...For the efficient conversion of L-tyrosine(L-Tyr)to tyrosol,which is an aromatic compound widely used in the pharmaceutical and chemical industries,a novel four-enzyme cascade pathway based on the Ehrlich pathway of Saccharomyces cerevisiae was designed and reconstructed in Escherichia coli.Then,the expression levels of the relevant enzymes were coordinated using a modular approach and gene duplication after the identification of the pyruvate decarboxylase from Candida tropicalis(CtPDC)as the rate-limiting enzymatic step.In situ product removal(ISPR)strategy with XAD4 resins was explored to avoid product inhibition and further improve tyrosol yield.As a result,the titer and conversion rate of tyrosol obtained were 35.7 g·L^(-1) and 93.6%,respectively,in a 3-L bioreactor.Results presented here provide a potential enzymatic process for industrial production of tyrosol from cheap amino acids.展开更多
3,4-Dihydroxy L-phenylalanine(L-DOPA)is considered a potent drug for the treatment of Parkinson disease.Physical and nutritional parameters where optimized by using Yarrowia lipolytica-NCIM 3450 to accomplished the hi...3,4-Dihydroxy L-phenylalanine(L-DOPA)is considered a potent drug for the treatment of Parkinson disease.Physical and nutritional parameters where optimized by using Yarrowia lipolytica-NCIM 3450 to accomplished the highest production of L-DOPA.Screenings of critical components were completed by using a Plackett–Burman design,while further optimization was carried out using the Box–Behnken design.The optimized factor levels predicted by the model were pH 6.1,1.659 g L^(-1)yeast extract,1.491 g L^(-1)L-tyrosine and 0.0290 g L^(-1)CuSO4.The predicted yield of L-DOPA with these levels was 1.319 g L^(-1),while actual yield obtained was 1.273 g L^(-1).The statistical analysis revealed that model is significant with F value 19.55 and R2 value 0.9514.This process resulted in a 3.594-fold increase in the yield of LDOPA.L-DOPA was confirmed by HPTLC and HPLC analysis.Thus,Yarrowia lipolytica-NCIM 3450 has potential to be a new source for the production of L-DOPA.展开更多
The absorption spectra of agueous L-tyrosine at various total ionic strengths were measured by UV-240 spectrophotometer at 298.2+/-0.2K and the standard third dissociation constant of L-tyrosine was determined from th...The absorption spectra of agueous L-tyrosine at various total ionic strengths were measured by UV-240 spectrophotometer at 298.2+/-0.2K and the standard third dissociation constant of L-tyrosine was determined from the spectra by linear extrapolation and polynomial approximation.展开更多
Two novel triflate precursors for radiolabelling of L-tyrosine in positron emission tomography (PET) for tumor imaging,O-(2-trifluoromethanesulfonyloxyethyl)-N-(tert-butoxycarbonyl)-L-tyrosine methyl ester 9a and O-(2...Two novel triflate precursors for radiolabelling of L-tyrosine in positron emission tomography (PET) for tumor imaging,O-(2-trifluoromethanesulfonyloxyethyl)-N-(tert-butoxycarbonyl)-L-tyrosine methyl ester 9a and O-(2-trifluoromethanesulfonyloxyethyl)-N-(tert-butoxycarbonyl)-L-tyrosine tert-butyl ester 9b,are synthesized. The triflate agent,9a or 9b,is prepared by esterification of methanol or transesterification of tert-butyl acetate with L-tyrosine,protection of the amine group with di-tert-butyl dicarbonate,alkylation with chlorohydrin,and triflation with trifluoromethanesulfonic anhydride in four steps with overall yields of 30% and 15%,respectively.展开更多
L-Tyrosine,an aromatic non-essential amino acid,is the raw material for many important chemical products,including levodopa,resveratrol,and hydroxytyrosol.It is widely used in the food,drug,and chemical industries.The...L-Tyrosine,an aromatic non-essential amino acid,is the raw material for many important chemical products,including levodopa,resveratrol,and hydroxytyrosol.It is widely used in the food,drug,and chemical industries.There are many studies on the synthesis of L-tyrosine by microorganisms,however,the low titer of L-tyrosine limited the industrial large-scale production.In order to enhance L-tyrosine production in Escherichia coli,the expression of key enzymes in the shikimate pathway was up-or down-regulated.The L-tyrosine transport system and the acetic acid biosynthesis pathway were modified to further enhance L-tyrosine production.In addition,the phosphoketolase pathway was introduced in combination with cofactor engineering to redirect carbon flux to the shikimate pathway.Finally,after adaptive laboratory evolution to low pH an optimal strain was obtained.The strain can produce 92.5 g/L of L-tyrosine in a 5-L fermenter in 62 h,with a yield of 0.266 g/g glucose.展开更多
A new serial chiral side-chain liquid crystal polysiloxanes containing L-Tyr structures were synthesized at room temperature. Both of them exhibited Sc phase at room temperature.
L-tyrosine,an aromatic amino acid,is an important upstream precursor for the synthesis of a series of valuable natural products such as flavonoids and phenolic acids.In recent years,regulation of the L‑tyrosine metabo...L-tyrosine,an aromatic amino acid,is an important upstream precursor for the synthesis of a series of valuable natural products such as flavonoids and phenolic acids.In recent years,regulation of the L‑tyrosine metabolic pathway has been devoted to enhancing the production of L-tyrosine and the derived bioactive compounds in microorganisms,usually by increasing the supply of precursors,blocking competitive routes,and modulating the transport system.Here,we reviewed the strategies to promote L-tyrosine production in microbial hosts and the common strategies to produce bioactive compounds in engineered Escherichia coli and Saccharomyces cerevisiae to better understand and utilize the L-tyrosine metabolic pathway for microbial overproduction of diverse valuable aromatic compounds in the future.展开更多
基金supported by the National Natural Science Foundation of China,No.30370537
文摘Adult BALB/c mice, individually housed, were stimulated with nine different stressors, arranged randomly, for 4 continuous weeks to generate an animal model of chronic stress. In chronically stressed mice, spontaneous locomotor activity was significantly decreased, escape latency in the Morris water maze test was prolonged, serum levels of total thyrotropin and total triiodothyronine were significantly decreased, and dopamine and norepinephrine content in the pallium, hippocampus and hypothalamus were significantly reduced. All of these changes were suppressed, to varying degrees, by L-tyrosine supplementation. These findings indicate that the neuroendocrine network plays an important role in chronic stress, and that L-tyrosine supplementation has therapeutic effects.
基金financially supported by the Fundamental Research Funds for the Central Universities (JUSRP21915)National Natural Science Foundation of China (22008089, 21878126)+2 种基金Provincial Natural Science Foundation of Jiangsu Province(BK20200622)the key technologies Research&Development Program of Jiangsu Province (BE2018623)the National First-Class Discipline Program of Light Industry Technology and Engineering(LITE2018-20)
文摘For the efficient conversion of L-tyrosine(L-Tyr)to tyrosol,which is an aromatic compound widely used in the pharmaceutical and chemical industries,a novel four-enzyme cascade pathway based on the Ehrlich pathway of Saccharomyces cerevisiae was designed and reconstructed in Escherichia coli.Then,the expression levels of the relevant enzymes were coordinated using a modular approach and gene duplication after the identification of the pyruvate decarboxylase from Candida tropicalis(CtPDC)as the rate-limiting enzymatic step.In situ product removal(ISPR)strategy with XAD4 resins was explored to avoid product inhibition and further improve tyrosol yield.As a result,the titer and conversion rate of tyrosol obtained were 35.7 g·L^(-1) and 93.6%,respectively,in a 3-L bioreactor.Results presented here provide a potential enzymatic process for industrial production of tyrosol from cheap amino acids.
文摘3,4-Dihydroxy L-phenylalanine(L-DOPA)is considered a potent drug for the treatment of Parkinson disease.Physical and nutritional parameters where optimized by using Yarrowia lipolytica-NCIM 3450 to accomplished the highest production of L-DOPA.Screenings of critical components were completed by using a Plackett–Burman design,while further optimization was carried out using the Box–Behnken design.The optimized factor levels predicted by the model were pH 6.1,1.659 g L^(-1)yeast extract,1.491 g L^(-1)L-tyrosine and 0.0290 g L^(-1)CuSO4.The predicted yield of L-DOPA with these levels was 1.319 g L^(-1),while actual yield obtained was 1.273 g L^(-1).The statistical analysis revealed that model is significant with F value 19.55 and R2 value 0.9514.This process resulted in a 3.594-fold increase in the yield of LDOPA.L-DOPA was confirmed by HPTLC and HPLC analysis.Thus,Yarrowia lipolytica-NCIM 3450 has potential to be a new source for the production of L-DOPA.
文摘The absorption spectra of agueous L-tyrosine at various total ionic strengths were measured by UV-240 spectrophotometer at 298.2+/-0.2K and the standard third dissociation constant of L-tyrosine was determined from the spectra by linear extrapolation and polynomial approximation.
文摘Two novel triflate precursors for radiolabelling of L-tyrosine in positron emission tomography (PET) for tumor imaging,O-(2-trifluoromethanesulfonyloxyethyl)-N-(tert-butoxycarbonyl)-L-tyrosine methyl ester 9a and O-(2-trifluoromethanesulfonyloxyethyl)-N-(tert-butoxycarbonyl)-L-tyrosine tert-butyl ester 9b,are synthesized. The triflate agent,9a or 9b,is prepared by esterification of methanol or transesterification of tert-butyl acetate with L-tyrosine,protection of the amine group with di-tert-butyl dicarbonate,alkylation with chlorohydrin,and triflation with trifluoromethanesulfonic anhydride in four steps with overall yields of 30% and 15%,respectively.
基金supported by the Foundation for Innovative Research Groups of the National Natural Science Foundation of China(32021005).
文摘L-Tyrosine,an aromatic non-essential amino acid,is the raw material for many important chemical products,including levodopa,resveratrol,and hydroxytyrosol.It is widely used in the food,drug,and chemical industries.There are many studies on the synthesis of L-tyrosine by microorganisms,however,the low titer of L-tyrosine limited the industrial large-scale production.In order to enhance L-tyrosine production in Escherichia coli,the expression of key enzymes in the shikimate pathway was up-or down-regulated.The L-tyrosine transport system and the acetic acid biosynthesis pathway were modified to further enhance L-tyrosine production.In addition,the phosphoketolase pathway was introduced in combination with cofactor engineering to redirect carbon flux to the shikimate pathway.Finally,after adaptive laboratory evolution to low pH an optimal strain was obtained.The strain can produce 92.5 g/L of L-tyrosine in a 5-L fermenter in 62 h,with a yield of 0.266 g/g glucose.
文摘A new serial chiral side-chain liquid crystal polysiloxanes containing L-Tyr structures were synthesized at room temperature. Both of them exhibited Sc phase at room temperature.
基金This work was supported by the National Natural Science Foundation of China(No.81673540,82173924)“Synthetic Biology-based biosynthesis of salvianolic acids”.
文摘L-tyrosine,an aromatic amino acid,is an important upstream precursor for the synthesis of a series of valuable natural products such as flavonoids and phenolic acids.In recent years,regulation of the L‑tyrosine metabolic pathway has been devoted to enhancing the production of L-tyrosine and the derived bioactive compounds in microorganisms,usually by increasing the supply of precursors,blocking competitive routes,and modulating the transport system.Here,we reviewed the strategies to promote L-tyrosine production in microbial hosts and the common strategies to produce bioactive compounds in engineered Escherichia coli and Saccharomyces cerevisiae to better understand and utilize the L-tyrosine metabolic pathway for microbial overproduction of diverse valuable aromatic compounds in the future.
