Tyrosol is a natural phenolic compound with antioxidant,anti-inflammatory and other biological activities,serving as an important precursor of high-value products such as hydroxytyrosol and salidroside.Therefore,the g...Tyrosol is a natural phenolic compound with antioxidant,anti-inflammatory and other biological activities,serving as an important precursor of high-value products such as hydroxytyrosol and salidroside.Therefore,the green and efficient biosynthesis of tyrosol and its derivatives has become a research hotspot in recent years.Building cell factories by metabolic engineering of microorganisms is a potential industrial production way,which has low costs and environmental friendliness.This paper introduces the biosynthesis pathway of tyrosol and presents the key regulated nodes in the de novo synthesis of tyrosol in Escherichia coli and Saccharomyces cerevisiae.In addition,this paper reviews the recent advances in metabolic engineering for the production of hydroxytyrosol and salidroside.This review can provide a reference for engineering the strains for the high-yield production of tyrosol and its derivatives.展开更多
Tyrosol is a pharmacologically active phenolic compound widely used in the medicine and chemical industries.Traditional methods of plant extraction are complicated and chemical synthesis of tyrosol is not commercially...Tyrosol is a pharmacologically active phenolic compound widely used in the medicine and chemical industries.Traditional methods of plant extraction are complicated and chemical synthesis of tyrosol is not commercially viable. In this study, a recombinant Escherichia coli strain was constructed by overexpressing the phenylpyruvate decarboxylase ARO10 from Saccharomyces cerevisiae, which could produce tyrosol from glucose. Furthermore,genes encoding key enzymes from the competing phenylalanine and tyrosine synthesis pathways and the repression protein TyrR were eliminated, and the resulting engineered strain generated 3.57 mmol·L^(-1) tyrosol from glucose. More significantly, codon optimization of ARO10 increased expression and tyrosol titer. Using the novel engineered strain expressing codon-optimized AR10 in shake-flask culture, 8.72 mmol·L^(-1) tyrosol was obtained after 48 h. Optimization of the induction conditions improved tyrosol production to 9.53 mmol·L^(-1)(1316.3 mg·L^(-1)). A higher titer of tyrosol was achieved by reconstruction of tyrosol synthetic pathway in E. coli.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
Tyrosol is an important component of pharmaceuticals,nutraceuticals,and cosmetics,and their biosynthetic pathways are currently a hot research topic.D-Erythrose 4-phosphate is a key precursor for the biosynthesis of t...Tyrosol is an important component of pharmaceuticals,nutraceuticals,and cosmetics,and their biosynthetic pathways are currently a hot research topic.D-Erythrose 4-phosphate is a key precursor for the biosynthesis of tyrosol in Saccharomyces cerevisiae.Hence,the flux of D-Erythrose 4-phosphate determined the yield of tyrosol synthesis.In this study,we first obtained an S.cerevisiae strain S19 with a tyrosol yield of 247.66 mg/L by metabolic engineering strategy.To increase the production of D-Erythrose 4-phosphate,highly active phospho-ketolase BA-C was obtained by bioinformatics combined with tyrosol yield assay.The key residue sites 183,217,and 320 were obtained by molecular docking,kinetic simulation,and tyrosol yield verification.After mutation,the highly efficient phosphoketolase BA-C^(His320Met) was obtained,with a 37.32%increase in enzyme activity.The tyrosol production of strain S26 with BA-C^(His320Arg) increased by 43.05%than strain S25 with BA-C and increased by 151.19%compared with the strain S19 without phosphoketolase in a 20 L fermenter.The mining and modification of phosphoketolase will provide strong support for the de novo synthesis of aromatic compounds.展开更多
The aim of the present study was to evaluate the effects of baobab seed washing and origin on the chemical composition of the oil extracted by pressing. Six (6) oil samples were obtained from seeds of three (3) geogra...The aim of the present study was to evaluate the effects of baobab seed washing and origin on the chemical composition of the oil extracted by pressing. Six (6) oil samples were obtained from seeds of three (3) geographical origins. The identification and quantification of fatty acids and the polyphenolic profile were carried out by GC-MS and HPLC-UV, respectively. Analysis of fatty acid methyl esters allowed the identification and quantification of 18 fatty acids. Oils from unwashed seeds were richer in palmitic (C16:0), stearic (C18:0), oleic (C18:1) and arachidic (C20:0) acids. In addition, HPLC-UV analysis at 279 nm shows that oils from unwashed seeds are richer in tyrosol, hydroxytyrosol and caffeic acid. With regard to the polyphenolic profile, gallic acid and quercetin were not detected in these baobab oils. Principal component analysis of fatty acid and phenolic compound content showed that oils from unwashed seeds would best preserve their chemical and associated potential bioactive characteristics.展开更多
By analyzing the key steps that restricted the industrial synthesis of salidroside, selective protection of tyrosol with different acylation reagents was adopted. The strategy facilitated the crystallization of interm...By analyzing the key steps that restricted the industrial synthesis of salidroside, selective protection of tyrosol with different acylation reagents was adopted. The strategy facilitated the crystallization of intermediates, which allowed the scalable synthesis of salidroside. It included a reaction of penta-O-acetyl-β-D-glucose with acyl protected tyrosol in the presence of Lewis acid catalyst（ZnCl2）, followed by deacylation under basic condition（NaOMe/MeOH） to give the salidroside. The total yield of this three-step reaction was 47%. Final product and intermediates were purified by recrystallization, which significantly reduced the cost and made the large scale synthesis feasible.展开更多
文摘Tyrosol is a natural phenolic compound with antioxidant,anti-inflammatory and other biological activities,serving as an important precursor of high-value products such as hydroxytyrosol and salidroside.Therefore,the green and efficient biosynthesis of tyrosol and its derivatives has become a research hotspot in recent years.Building cell factories by metabolic engineering of microorganisms is a potential industrial production way,which has low costs and environmental friendliness.This paper introduces the biosynthesis pathway of tyrosol and presents the key regulated nodes in the de novo synthesis of tyrosol in Escherichia coli and Saccharomyces cerevisiae.In addition,this paper reviews the recent advances in metabolic engineering for the production of hydroxytyrosol and salidroside.This review can provide a reference for engineering the strains for the high-yield production of tyrosol and its derivatives.
基金Supported by the Fundamental Research Funds for the Central Universities(JUSRP51611A,JUSRP51504)the Natural Science Foundation of Jiangsu Province(BK20171138)+1 种基金the National High Technology Research and Development Program of China(863 program,2013AA102101-5)the 111 Project(No.1112-06)
文摘Tyrosol is a pharmacologically active phenolic compound widely used in the medicine and chemical industries.Traditional methods of plant extraction are complicated and chemical synthesis of tyrosol is not commercially viable. In this study, a recombinant Escherichia coli strain was constructed by overexpressing the phenylpyruvate decarboxylase ARO10 from Saccharomyces cerevisiae, which could produce tyrosol from glucose. Furthermore,genes encoding key enzymes from the competing phenylalanine and tyrosine synthesis pathways and the repression protein TyrR were eliminated, and the resulting engineered strain generated 3.57 mmol·L^(-1) tyrosol from glucose. More significantly, codon optimization of ARO10 increased expression and tyrosol titer. Using the novel engineered strain expressing codon-optimized AR10 in shake-flask culture, 8.72 mmol·L^(-1) tyrosol was obtained after 48 h. Optimization of the induction conditions improved tyrosol production to 9.53 mmol·L^(-1)(1316.3 mg·L^(-1)). A higher titer of tyrosol was achieved by reconstruction of tyrosol synthetic pathway in E. coli.
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.
基金supported by the National Natural Science Foundations of China(Grant Nos.31871789 and 41876114)the key project of Hubei Provincial Department of Education(T2022011)the Natural Science Foundation of Hubei Province(No.2024AFB803).
文摘Tyrosol is an important component of pharmaceuticals,nutraceuticals,and cosmetics,and their biosynthetic pathways are currently a hot research topic.D-Erythrose 4-phosphate is a key precursor for the biosynthesis of tyrosol in Saccharomyces cerevisiae.Hence,the flux of D-Erythrose 4-phosphate determined the yield of tyrosol synthesis.In this study,we first obtained an S.cerevisiae strain S19 with a tyrosol yield of 247.66 mg/L by metabolic engineering strategy.To increase the production of D-Erythrose 4-phosphate,highly active phospho-ketolase BA-C was obtained by bioinformatics combined with tyrosol yield assay.The key residue sites 183,217,and 320 were obtained by molecular docking,kinetic simulation,and tyrosol yield verification.After mutation,the highly efficient phosphoketolase BA-C^(His320Met) was obtained,with a 37.32%increase in enzyme activity.The tyrosol production of strain S26 with BA-C^(His320Arg) increased by 43.05%than strain S25 with BA-C and increased by 151.19%compared with the strain S19 without phosphoketolase in a 20 L fermenter.The mining and modification of phosphoketolase will provide strong support for the de novo synthesis of aromatic compounds.
文摘The aim of the present study was to evaluate the effects of baobab seed washing and origin on the chemical composition of the oil extracted by pressing. Six (6) oil samples were obtained from seeds of three (3) geographical origins. The identification and quantification of fatty acids and the polyphenolic profile were carried out by GC-MS and HPLC-UV, respectively. Analysis of fatty acid methyl esters allowed the identification and quantification of 18 fatty acids. Oils from unwashed seeds were richer in palmitic (C16:0), stearic (C18:0), oleic (C18:1) and arachidic (C20:0) acids. In addition, HPLC-UV analysis at 279 nm shows that oils from unwashed seeds are richer in tyrosol, hydroxytyrosol and caffeic acid. With regard to the polyphenolic profile, gallic acid and quercetin were not detected in these baobab oils. Principal component analysis of fatty acid and phenolic compound content showed that oils from unwashed seeds would best preserve their chemical and associated potential bioactive characteristics.
基金the National Basic Research Program of China(973 Program,Grant No.2012CB822100)the National Key Technology R&D Program"New Drug Innovation"of China(Grant No.2012ZX09502001-001)the National Natural Science Foundation of China(Grant No.21232002,21072016 and 21072017)
文摘By analyzing the key steps that restricted the industrial synthesis of salidroside, selective protection of tyrosol with different acylation reagents was adopted. The strategy facilitated the crystallization of intermediates, which allowed the scalable synthesis of salidroside. It included a reaction of penta-O-acetyl-β-D-glucose with acyl protected tyrosol in the presence of Lewis acid catalyst（ZnCl2）, followed by deacylation under basic condition（NaOMe/MeOH） to give the salidroside. The total yield of this three-step reaction was 47%. Final product and intermediates were purified by recrystallization, which significantly reduced the cost and made the large scale synthesis feasible.
