Basal cell carcinoma is the most common form of skin cancer and the most frequently occurring form of all cancers. Conventional treatments to remove or destroy basal cell carcinoma are indiscriminate and also remove o...Basal cell carcinoma is the most common form of skin cancer and the most frequently occurring form of all cancers. Conventional treatments to remove or destroy basal cell carcinoma are indiscriminate and also remove or destroy normal skin cells resulting in compromised cosmetic outcomes. Consequences of these treatments include body-image issues, anxiety, post-traumatic stress disorder, depression, and poorer quality of social and family life. A progressive topical cream formulation, Curaderm, containing the natural BEC glycoalkaloids, have shown to have advantages over conventional treatments. However, comprehensive clinical features of the skin cancer lesions during treatment with Curaderm have to date not been reported. This report shows that using unpublished data from a large number of patients with varying sizes, types and locations of basal cell carcinomas when treated with Curaderm in a phase 3 trial, an initial increase in size of the lesions occur, followed by a reverse course, leading to complete removal of the skin cancer. The specificity and mode of action of Curaderm explains the superior cosmetic outcomes when compared with conventional therapies.展开更多
Steroidal glycoalkaloids（SGAs） are nitrogen-containing secondary metabolites of the Solanum species,which are known to have large chemical and bioactive diversity in nature.While recent effort and development on LC/...Steroidal glycoalkaloids（SGAs） are nitrogen-containing secondary metabolites of the Solanum species,which are known to have large chemical and bioactive diversity in nature.While recent effort and development on LC/MS techniques for SGA profiling have elucidated the main pathways of SGA metabolism in tomato,the problem of peak annotation still remains due to the vast diversity of chemical structure and similar on overlapping of chemical formula.Here we provide a case study of peak classification and annotation approach by integration of species and tissue specificities of SGA accumulation for provision of comprehensive pathways of SGA biosynthesis.In order to elucidate natural diversity of SGA biosynthesis,a total of 169 putative SGAs found in eight tomato accessions（Soianum lycopersicum, S.pimpinellifolium, S.cheesmaniae, S.chmielewskii, S.neorickii,S.peruvianum,S.habrochaites,S.pennellii） and four tissue types were used for correlation analysis.The results obtained in this study contribute annotation and classification of SGAs as well as detecting putative novel biosynthetic branch points.As such this represents a novel strategy for peak annotation for plant secondary metabolites.展开更多
Steroidal glycoalkaloids(SGAs)are specialized metabolites produced by hundreds of Solanum species,including important vegetable crops such as tomato,potato,and eggplant.Although it has been known that SGAs play import...Steroidal glycoalkaloids(SGAs)are specialized metabolites produced by hundreds of Solanum species,including important vegetable crops such as tomato,potato,and eggplant.Although it has been known that SGAs play important roles in defense in plants and“anti-nutritional"effects(e.g.,toxicity and bitterness)to humans,many of these molecules have documented anti-cancer,anti-microbial,antiinflammatory,anti-viral,and anti-pyretic activities.Among these,α-solasonine andα-solamargine isolated from black nightshade(Solanum nigrum)are reported to have potent anti-tumor,anti-proliferative,and anti-inflammatory activities.Notably,α-solasonine andα-solamargine,along with the core steroidal aglycone solasodine,are the most widespread SGAs produced among the Solanum plants.However,it is still unknown how plants synthesize these bioactive steroidal molecules.Through comparative metabolomictranscriptome-guided approach,biosynthetic logic,combinatorial expression in Nicotiana benthamiana,and functional recombinant enzyme assays,here we report the discovery of 12 enzymes from S.nigrum that converts the starting cholesterol precursorto solasodine aglycone,and the downstreamα-solasonine,α-solamargine,and malonyl-solamargine SGA products.We further identified six enzymes from cultivated eggplant that catalyze the production ofα-solasonine,α-solamargine,and malonyl-solamargine SGAs from solasodine aglycone via glycosylation and atypical malonylation decorations.Our work provides the gene tool box and platform for engineering the production of high-value,steroidal bioactive molecules inheterologoushosts usingsyntheticbiology.展开更多
Glycoalkaloids（GAS） have important biological and pharmaceutical activities, in order to study the relationship between the structures and the activities of carbohydrate chains, two natural glycoalkaloids, chaconine...Glycoalkaloids（GAS） have important biological and pharmaceutical activities, in order to study the relationship between the structures and the activities of carbohydrate chains, two natural glycoalkaloids, chaconine （compound 1 ） and solanine（ compound 2） , were isolated from potato stems and leaves（ Solanum tuberosum L. ）. The selective sulfation to the 6-hydroxy groups of chaeonine and solanine was carried out in a strategy by the use of protective groups. The 6-hydroxyl groups of the sugar chains in chaconine and solanine were protected with 4,4＇-dimethoxytrityl（DMT） while the other hydroxyl groups were acetylated. The protective group DMT was removed by using 0. 5% TFA in dichloromethane, The free 6-hydroxyl groups were sulfated by chlorosulfonic acid pyridine to give 6-O-sulfated products. After the acetyl groups were removed, the final products obtained were sulfated chaconine and sulfated solanine.^ 13C NMR spectra confirmed that chaconine and solanine were sulfated at O6 of the carbohydrate moiety.展开更多
文摘Basal cell carcinoma is the most common form of skin cancer and the most frequently occurring form of all cancers. Conventional treatments to remove or destroy basal cell carcinoma are indiscriminate and also remove or destroy normal skin cells resulting in compromised cosmetic outcomes. Consequences of these treatments include body-image issues, anxiety, post-traumatic stress disorder, depression, and poorer quality of social and family life. A progressive topical cream formulation, Curaderm, containing the natural BEC glycoalkaloids, have shown to have advantages over conventional treatments. However, comprehensive clinical features of the skin cancer lesions during treatment with Curaderm have to date not been reported. This report shows that using unpublished data from a large number of patients with varying sizes, types and locations of basal cell carcinomas when treated with Curaderm in a phase 3 trial, an initial increase in size of the lesions occur, followed by a reverse course, leading to complete removal of the skin cancer. The specificity and mode of action of Curaderm explains the superior cosmetic outcomes when compared with conventional therapies.
基金supported by Specialized ResearchFund for the Doctoral Program of Higher Education(20070200004)the Natural Science Foundation of Jilin Province (20040546)
基金financially supported by the Potsdam university(K.S.)the Max Planck Society(to L.P.,A.F.,and T.T.)+1 种基金an Alexander von Humboldt grant(to T.T.)the European Commission's Directorate-General for Research within the 7~(th) Framework Program(FP7/2007-2013) under grant agreements 270089(MULTIBIOPRO)
文摘Steroidal glycoalkaloids（SGAs） are nitrogen-containing secondary metabolites of the Solanum species,which are known to have large chemical and bioactive diversity in nature.While recent effort and development on LC/MS techniques for SGA profiling have elucidated the main pathways of SGA metabolism in tomato,the problem of peak annotation still remains due to the vast diversity of chemical structure and similar on overlapping of chemical formula.Here we provide a case study of peak classification and annotation approach by integration of species and tissue specificities of SGA accumulation for provision of comprehensive pathways of SGA biosynthesis.In order to elucidate natural diversity of SGA biosynthesis,a total of 169 putative SGAs found in eight tomato accessions（Soianum lycopersicum, S.pimpinellifolium, S.cheesmaniae, S.chmielewskii, S.neorickii,S.peruvianum,S.habrochaites,S.pennellii） and four tissue types were used for correlation analysis.The results obtained in this study contribute annotation and classification of SGAs as well as detecting putative novel biosynthetic branch points.As such this represents a novel strategy for peak annotation for plant secondary metabolites.
基金the Fulbright Us Student Program,which is sponsored by The US Department of State and the German-American Fulbright Commission.We thank Prof.M.Court for UGT nomenclature assignment.N.benthamiana and green unripe and purple ripe S.nigrum berries used in the main and supplementary figures were generated in BioRender.We kindly acknowledge the Max Planck Society and the European Research Council(788301)for funding.
文摘Steroidal glycoalkaloids(SGAs)are specialized metabolites produced by hundreds of Solanum species,including important vegetable crops such as tomato,potato,and eggplant.Although it has been known that SGAs play important roles in defense in plants and“anti-nutritional"effects(e.g.,toxicity and bitterness)to humans,many of these molecules have documented anti-cancer,anti-microbial,antiinflammatory,anti-viral,and anti-pyretic activities.Among these,α-solasonine andα-solamargine isolated from black nightshade(Solanum nigrum)are reported to have potent anti-tumor,anti-proliferative,and anti-inflammatory activities.Notably,α-solasonine andα-solamargine,along with the core steroidal aglycone solasodine,are the most widespread SGAs produced among the Solanum plants.However,it is still unknown how plants synthesize these bioactive steroidal molecules.Through comparative metabolomictranscriptome-guided approach,biosynthetic logic,combinatorial expression in Nicotiana benthamiana,and functional recombinant enzyme assays,here we report the discovery of 12 enzymes from S.nigrum that converts the starting cholesterol precursorto solasodine aglycone,and the downstreamα-solasonine,α-solamargine,and malonyl-solamargine SGA products.We further identified six enzymes from cultivated eggplant that catalyze the production ofα-solasonine,α-solamargine,and malonyl-solamargine SGAs from solasodine aglycone via glycosylation and atypical malonylation decorations.Our work provides the gene tool box and platform for engineering the production of high-value,steroidal bioactive molecules inheterologoushosts usingsyntheticbiology.
文摘Glycoalkaloids（GAS） have important biological and pharmaceutical activities, in order to study the relationship between the structures and the activities of carbohydrate chains, two natural glycoalkaloids, chaconine （compound 1 ） and solanine（ compound 2） , were isolated from potato stems and leaves（ Solanum tuberosum L. ）. The selective sulfation to the 6-hydroxy groups of chaeonine and solanine was carried out in a strategy by the use of protective groups. The 6-hydroxyl groups of the sugar chains in chaconine and solanine were protected with 4,4＇-dimethoxytrityl（DMT） while the other hydroxyl groups were acetylated. The protective group DMT was removed by using 0. 5% TFA in dichloromethane, The free 6-hydroxyl groups were sulfated by chlorosulfonic acid pyridine to give 6-O-sulfated products. After the acetyl groups were removed, the final products obtained were sulfated chaconine and sulfated solanine.^ 13C NMR spectra confirmed that chaconine and solanine were sulfated at O6 of the carbohydrate moiety.
