Anthracnose is a fungal disease caused by Colletotrichum gloeosporioides, which is one of themain causes of mango rotting and deterioration, so it is important to control anthracnose.The calendula essential oil is a v...Anthracnose is a fungal disease caused by Colletotrichum gloeosporioides, which is one of themain causes of mango rotting and deterioration, so it is important to control anthracnose.The calendula essential oil is a volatile constituent extracted from calendula officinalis,which has attracted attention from researchers worldwide because of its excellentantimicrobial and antioxidant activities. However, studies on the antifungal mechanism ofcalendula essential oil and its active constituents against C. gloeosporioides have not beenreported. Therefore, this paper preliminarily evaluated the anti-C. gloeosporioides activity ofcalendula officinalis essential oil and its main active constituent geraniol. We found thatgeraniol induced a reactive oxygen species (ROS) burst by modulating the expression of theNADPH oxidase subunit NoxR gene. Moreover, the activities of catalase (CAT), peroxidase(POD), superoxide dismutase (SOD), and glutathione peroxidase (GSH) increased withincreasing geraniol concentration, which demonstrated that the pro-oxidant property ofgeraniol was one of the main reasons for its inhibition of C. gloeosporioides growth.Furthermore, we found that geraniol induced apoptosis in C. gloeosporioides in adose-dependent manner. In conclusion, these results provide a new reference for futureexploration of the antifungal mechanism of geraniol against C. gloeosporioides.展开更多
Geraniol is a monoterpenoid alcohol with various applications in food,cosmetics,and healthcare.Corynebacterium glutamicum is a potential platform for terpenoids production because it harbors the methylerythritol phosp...Geraniol is a monoterpenoid alcohol with various applications in food,cosmetics,and healthcare.Corynebacterium glutamicum is a potential platform for terpenoids production because it harbors the methylerythritol phosphate pathway.To engineer C.glutamicum to produce geraniol,two different truncated geraniol synthases (GESs) were respectively expressed,and strain LX02 expressing the truncated GESs from Valeriana officinalis (t Vo GES) produced 0.3 mg/L of geraniol.Then,three geranyl diphosphate synthases (GPPSs) were combinatorially co-expressed with t Vo GES to improve geraniol production.The amounts of produced geraniol were all higher than that produced by strain LX02.Strain LX03 co-expressing ERG20 F96W–N127W (ERG20 WW) and t Vo GES produced the highest amount,5.4 mg/L.Subsequently,the co-overexpression of1-deoxy-D-xylulose-5-phosphate synthase (dxs) and isopentenyl diphosphate isomerase (idi) further increased the production to 12.2 mg/L in strain LX03.Lastly,the production of geraniol was increased to 15.2 mg/L via fermentation optimization.To our knowledge,this is the first report on the engineering of C.glutamicum to produce geraniol and thus can serve as a reference for other monoterpenoid production studies.展开更多
Catharanthus roseus contains important anti-tumor terpenoid indole alkaloids (TIAs) such as vinblastine and vincristine. Cytochrome P450 enzyme geraniol 10-hydroxylase (G10H) is a putative rate-limiting enzyme involve...Catharanthus roseus contains important anti-tumor terpenoid indole alkaloids (TIAs) such as vinblastine and vincristine. Cytochrome P450 enzyme geraniol 10-hydroxylase (G10H) is a putative rate-limiting enzyme involved in the TIAs biosynthetic pathway in C. roseus. In this study the g10h gene driven by the cauliflower mosaic virus 35S (CaMV 35S) promoter was introduced into C. roseus through Agrobacterium-mediated transformation. The integration and overexpression of the target gene (g10h) in hairy root lines were confirmed by polymerase chain reaction and RT-QPCR analysis respectively. Overexpression of g10h in transgenic hairy root lines significantly enhanced the accumulations of monomeric alkaloid ajmalicine and dimeric alkaloids, vincristine and vinblastine. Total TIAs production in hairy roots reached (9.51) mg/g DW, over 3-fold higher than that in the untransformed root lines. This is the first report that engineering of g10h into TIAs-producing plant species results in significant enhancement of TIAs accumulation in cultured hairy roots. This study demonstrates that the putative rate-limiting step catalyzed by G10H is indeed the real rate-limiting step involved in the TIAs biosynthetic pathway in C. roseus, which is one of the key targets for promoting TIAs production by genetic engineering.展开更多
The reduction of geraniol to citronellol is the first step for the synthesis of natural phytol in the production of tocopherols and natural vitamin K.Baker's yeast was used in the bioreduction described above as a...The reduction of geraniol to citronellol is the first step for the synthesis of natural phytol in the production of tocopherols and natural vitamin K.Baker's yeast was used in the bioreduction described above as a whole-cell biocatalyst.However,the enzyme responsible for the reduction of geraniol to citronellol is not yet known.Four old yellow enzyme(OYE)genes were cloned from yeast and plants,and expressed in Escherichia coli for a high level of recombinant proteins.The recombinant protein displayed a catalytic activity of converting geraniol to citronellol as a sole product verified by GC-MS analyses.The recombinant OYE2 intact cells were found to show 3.7 and 1.9-fold higher activity than that of yeast cells and the recombinant crude extracts,respectively.Compared to the recombinant fusion enzyme,the entrokinase-cleaved enzyme displayed nearly identical activity for geraniol reduction.To our knowledge,this is the first enzyme identified to catalyze the formation of citronellol from geraniol by reducing the allylic alcohol double bond,which is normally known as inactivating group for the old yellow enzymes.展开更多
Terpenes are one of the largest and most diversified families of natural compounds. Although they have found numerous industrial applications, the molecular basis of their synthesis in plants has, until now, not been ...Terpenes are one of the largest and most diversified families of natural compounds. Although they have found numerous industrial applications, the molecular basis of their synthesis in plants has, until now, not been fully understood. Plant genomes have been shown to contain dozens of terpene synthase (TPS) genes, however knowledge of their amino-acidic protein sequence in not sufficient to predict which terpene(s) will be produced by a particular enzyme. In order to investigate the structural basis of a TPS specificity, we performed site directed mutations in the geraniol synthase from Ocimum basilicum. The results obtained suggest that a specific region on the catalytic site plays an important role in GPP transformation, either by stabilizing the GPP substrate on the catalytic site, or by enabling its transformation into a monoterpenol via an intermediate carbocation.展开更多
Objective:To explore the effect of geraniol on cyclophosphamide-induced cardiotoxicity.Methods:Mice were divided into five groups:the control group,the cyclophosphamide group(200 mg/kg cyclophosphamide,i.p.on day 7),t...Objective:To explore the effect of geraniol on cyclophosphamide-induced cardiotoxicity.Methods:Mice were divided into five groups:the control group,the cyclophosphamide group(200 mg/kg cyclophosphamide,i.p.on day 7),the group treated with geraniol 100 and 200 mg/kg from day 1 to day 14,along with a single dose of cyclophosphamide on day 7,and the geraniol alone group(200 mg/kg geraniol from day 1 to day 14).At the end of the study,animals were sacrificed,and blood and heart were collected and analyzed for biochemical,histopathological,and immunohistochemical changes.Results:Treatment with 200 mg/kg geraniol significantly reduced the levels of cardiac injury markers,malondialdehyde,and inflammatory and apoptotic markers,while increasing antioxidant activities in mice with cyclophosphamide-induced cardiotoxicity.Moreover,it remarkably alleviated histopathological aberrations in cardiac tissue.Conclusions:Geraniol attenuates cyclophosphamide-induced cardiotoxicity via antioxidant,anti-inflammatory,and antiapoptotic effects.展开更多
Geraniol is an acyclic monoterpenoid compound,which exists widely in aromatic plants.Geraniol has antibacterial and anti-inflammatory effects.Recently,it has been found that geraniol has a strong effect on improving i...Geraniol is an acyclic monoterpenoid compound,which exists widely in aromatic plants.Geraniol has antibacterial and anti-inflammatory effects.Recently,it has been found that geraniol has a strong effect on improving immune function and anti-tumor.Many experimental evidences support that geraniol has a good effect on the treatment or prevention of different types of tumors,such as breast cancer,lung cancer,liver cancer,pancreatic cancer,colon cancer,prostate cancer,etc.it also has a synergistic anti-cancer effect with many anti-cancer drugs,revealing the mechanism of its more complex anti-tumor pharmacological action System.In this review,we summarized a variety of anti-cancer signaling pathways and targets.Geraniol is considered to be a safe,effective and promising multi-target anti-cancer drug,which is expected to become an important force in the anti-cancer of traditional Chinese medicine.展开更多
目的:基于生物信息学探讨香叶醇靶向MAPK1(Mitogen-Activated Protein Kinase 1)抗骨肉瘤的机制。方法:从TCMSP(Traditional Chinese Medicine Systems)数据库下载人类软骨肉瘤相关基因数据集GSE16088数据集,其中GSE16088数据集中共有8...目的:基于生物信息学探讨香叶醇靶向MAPK1(Mitogen-Activated Protein Kinase 1)抗骨肉瘤的机制。方法:从TCMSP(Traditional Chinese Medicine Systems)数据库下载人类软骨肉瘤相关基因数据集GSE16088数据集,其中GSE16088数据集中共有8例样本,其中健康人群4例、骨肉瘤患者4例,从铁死亡数据库筛选铁死亡相关基因并对香叶醇靶基因与铁死亡相关基因取交集,从TARGET数据库中分析骨肉瘤中MAPK1与铁死亡核心调控子GPX4(Glutathione Peroxidase 4)的相关性。结果:通过TCMSP数据库确认了香叶醇的38个可能靶点,通过铁死亡数据库确认出567个铁死亡相关基因;香叶醇靶基因与铁死亡相关基因取交集确认五个香叶醇靶向的铁死亡基因:HMOX1(Heme Oxygenase 1),MAPK1,TP53(Tumor Protein P53),PTGS2(Prostaglandin-Endoperoxide Synthase 2),HRAS(Harvey Rat Sarcoma Viral Oncogene Homolog)通过GSE16088数据集分析发现与正常组织相比,MAPK1在骨肉瘤中显著高表达,TARGET数据库分析表明,骨肉瘤中MAPK1与铁死亡核心调控子GPX4正相关。结论:香叶醇可能通过靶向MAPK1调控铁死亡过程,从而发挥抗骨肉瘤的作用。展开更多
基金the National Natural Science Foundation of China(32202192)The special fund for Taishan Scholars project(tsqn202211195).
文摘Anthracnose is a fungal disease caused by Colletotrichum gloeosporioides, which is one of themain causes of mango rotting and deterioration, so it is important to control anthracnose.The calendula essential oil is a volatile constituent extracted from calendula officinalis,which has attracted attention from researchers worldwide because of its excellentantimicrobial and antioxidant activities. However, studies on the antifungal mechanism ofcalendula essential oil and its active constituents against C. gloeosporioides have not beenreported. Therefore, this paper preliminarily evaluated the anti-C. gloeosporioides activity ofcalendula officinalis essential oil and its main active constituent geraniol. We found thatgeraniol induced a reactive oxygen species (ROS) burst by modulating the expression of theNADPH oxidase subunit NoxR gene. Moreover, the activities of catalase (CAT), peroxidase(POD), superoxide dismutase (SOD), and glutathione peroxidase (GSH) increased withincreasing geraniol concentration, which demonstrated that the pro-oxidant property ofgeraniol was one of the main reasons for its inhibition of C. gloeosporioides growth.Furthermore, we found that geraniol induced apoptosis in C. gloeosporioides in adose-dependent manner. In conclusion, these results provide a new reference for futureexploration of the antifungal mechanism of geraniol against C. gloeosporioides.
基金supported by the National Natural Science Foundation of China (No. 21878220)。
文摘Geraniol is a monoterpenoid alcohol with various applications in food,cosmetics,and healthcare.Corynebacterium glutamicum is a potential platform for terpenoids production because it harbors the methylerythritol phosphate pathway.To engineer C.glutamicum to produce geraniol,two different truncated geraniol synthases (GESs) were respectively expressed,and strain LX02 expressing the truncated GESs from Valeriana officinalis (t Vo GES) produced 0.3 mg/L of geraniol.Then,three geranyl diphosphate synthases (GPPSs) were combinatorially co-expressed with t Vo GES to improve geraniol production.The amounts of produced geraniol were all higher than that produced by strain LX02.Strain LX03 co-expressing ERG20 F96W–N127W (ERG20 WW) and t Vo GES produced the highest amount,5.4 mg/L.Subsequently,the co-overexpression of1-deoxy-D-xylulose-5-phosphate synthase (dxs) and isopentenyl diphosphate isomerase (idi) further increased the production to 12.2 mg/L in strain LX03.Lastly,the production of geraniol was increased to 15.2 mg/L via fermentation optimization.To our knowledge,this is the first report on the engineering of C.glutamicum to produce geraniol and thus can serve as a reference for other monoterpenoid production studies.
基金Item supported by China national"863"high-tech program (2002AA212191)China ministry of educa-tion and science and technology commission of Shanghai(04XD14011)
文摘Catharanthus roseus contains important anti-tumor terpenoid indole alkaloids (TIAs) such as vinblastine and vincristine. Cytochrome P450 enzyme geraniol 10-hydroxylase (G10H) is a putative rate-limiting enzyme involved in the TIAs biosynthetic pathway in C. roseus. In this study the g10h gene driven by the cauliflower mosaic virus 35S (CaMV 35S) promoter was introduced into C. roseus through Agrobacterium-mediated transformation. The integration and overexpression of the target gene (g10h) in hairy root lines were confirmed by polymerase chain reaction and RT-QPCR analysis respectively. Overexpression of g10h in transgenic hairy root lines significantly enhanced the accumulations of monomeric alkaloid ajmalicine and dimeric alkaloids, vincristine and vinblastine. Total TIAs production in hairy roots reached (9.51) mg/g DW, over 3-fold higher than that in the untransformed root lines. This is the first report that engineering of g10h into TIAs-producing plant species results in significant enhancement of TIAs accumulation in cultured hairy roots. This study demonstrates that the putative rate-limiting step catalyzed by G10H is indeed the real rate-limiting step involved in the TIAs biosynthetic pathway in C. roseus, which is one of the key targets for promoting TIAs production by genetic engineering.
基金This work was supported by grants from the Ministry of Science and Technology of China(2007CB108802)State Key Laboratory of Phytochemistry and Plant Resources in West China(P2008-ZZ16,P2009-ZZ02).
文摘The reduction of geraniol to citronellol is the first step for the synthesis of natural phytol in the production of tocopherols and natural vitamin K.Baker's yeast was used in the bioreduction described above as a whole-cell biocatalyst.However,the enzyme responsible for the reduction of geraniol to citronellol is not yet known.Four old yellow enzyme(OYE)genes were cloned from yeast and plants,and expressed in Escherichia coli for a high level of recombinant proteins.The recombinant protein displayed a catalytic activity of converting geraniol to citronellol as a sole product verified by GC-MS analyses.The recombinant OYE2 intact cells were found to show 3.7 and 1.9-fold higher activity than that of yeast cells and the recombinant crude extracts,respectively.Compared to the recombinant fusion enzyme,the entrokinase-cleaved enzyme displayed nearly identical activity for geraniol reduction.To our knowledge,this is the first enzyme identified to catalyze the formation of citronellol from geraniol by reducing the allylic alcohol double bond,which is normally known as inactivating group for the old yellow enzymes.
文摘Terpenes are one of the largest and most diversified families of natural compounds. Although they have found numerous industrial applications, the molecular basis of their synthesis in plants has, until now, not been fully understood. Plant genomes have been shown to contain dozens of terpene synthase (TPS) genes, however knowledge of their amino-acidic protein sequence in not sufficient to predict which terpene(s) will be produced by a particular enzyme. In order to investigate the structural basis of a TPS specificity, we performed site directed mutations in the geraniol synthase from Ocimum basilicum. The results obtained suggest that a specific region on the catalytic site plays an important role in GPP transformation, either by stabilizing the GPP substrate on the catalytic site, or by enabling its transformation into a monoterpenol via an intermediate carbocation.
基金The Deanship of Scientific Research at King Abdulaziz University,Jeddah,Saudi Arabia has funded this project under grant no.RG-21-166-43.
文摘Objective:To explore the effect of geraniol on cyclophosphamide-induced cardiotoxicity.Methods:Mice were divided into five groups:the control group,the cyclophosphamide group(200 mg/kg cyclophosphamide,i.p.on day 7),the group treated with geraniol 100 and 200 mg/kg from day 1 to day 14,along with a single dose of cyclophosphamide on day 7,and the geraniol alone group(200 mg/kg geraniol from day 1 to day 14).At the end of the study,animals were sacrificed,and blood and heart were collected and analyzed for biochemical,histopathological,and immunohistochemical changes.Results:Treatment with 200 mg/kg geraniol significantly reduced the levels of cardiac injury markers,malondialdehyde,and inflammatory and apoptotic markers,while increasing antioxidant activities in mice with cyclophosphamide-induced cardiotoxicity.Moreover,it remarkably alleviated histopathological aberrations in cardiac tissue.Conclusions:Geraniol attenuates cyclophosphamide-induced cardiotoxicity via antioxidant,anti-inflammatory,and antiapoptotic effects.
文摘Ferric chloride catalyzes the isomerization and cyclization of geraniol, linalool and nerol in acetonitrile giving a-terpineol in good to high yields.
文摘Geraniol is an acyclic monoterpenoid compound,which exists widely in aromatic plants.Geraniol has antibacterial and anti-inflammatory effects.Recently,it has been found that geraniol has a strong effect on improving immune function and anti-tumor.Many experimental evidences support that geraniol has a good effect on the treatment or prevention of different types of tumors,such as breast cancer,lung cancer,liver cancer,pancreatic cancer,colon cancer,prostate cancer,etc.it also has a synergistic anti-cancer effect with many anti-cancer drugs,revealing the mechanism of its more complex anti-tumor pharmacological action System.In this review,we summarized a variety of anti-cancer signaling pathways and targets.Geraniol is considered to be a safe,effective and promising multi-target anti-cancer drug,which is expected to become an important force in the anti-cancer of traditional Chinese medicine.
文摘目的:基于生物信息学探讨香叶醇靶向MAPK1(Mitogen-Activated Protein Kinase 1)抗骨肉瘤的机制。方法:从TCMSP(Traditional Chinese Medicine Systems)数据库下载人类软骨肉瘤相关基因数据集GSE16088数据集,其中GSE16088数据集中共有8例样本,其中健康人群4例、骨肉瘤患者4例,从铁死亡数据库筛选铁死亡相关基因并对香叶醇靶基因与铁死亡相关基因取交集,从TARGET数据库中分析骨肉瘤中MAPK1与铁死亡核心调控子GPX4(Glutathione Peroxidase 4)的相关性。结果:通过TCMSP数据库确认了香叶醇的38个可能靶点,通过铁死亡数据库确认出567个铁死亡相关基因;香叶醇靶基因与铁死亡相关基因取交集确认五个香叶醇靶向的铁死亡基因:HMOX1(Heme Oxygenase 1),MAPK1,TP53(Tumor Protein P53),PTGS2(Prostaglandin-Endoperoxide Synthase 2),HRAS(Harvey Rat Sarcoma Viral Oncogene Homolog)通过GSE16088数据集分析发现与正常组织相比,MAPK1在骨肉瘤中显著高表达,TARGET数据库分析表明,骨肉瘤中MAPK1与铁死亡核心调控子GPX4正相关。结论:香叶醇可能通过靶向MAPK1调控铁死亡过程,从而发挥抗骨肉瘤的作用。
