Missing enzymes in the biosynthesis of the anticancer drug vinblastine in Madagascar periwinkle
Caputi, L., Franke, J., Farrow, S. C., Chung, K., Payne, R. M. E., Nguyen, T.-D., Dang, T.-T. T., Soares Teto Carqueijeiro, I., Koudounas, K., Duge de Bernonville, T., Ameyaw, B., Jones, D. M., Vieira, I. J. C., Courdavault, V., OConnor, S. E.
American Association for the Advancement of Science (AAAS)
Published 2018
American Association for the Advancement of Science (AAAS)
Published 2018
| Publication Date: |
2018-06-15
|
|---|---|
| Publisher: |
American Association for the Advancement of Science (AAAS)
|
| Print ISSN: |
0036-8075
|
| Electronic ISSN: |
1095-9203
|
| Topics: |
Biology
Chemistry and Pharmacology
Geosciences
Computer Science
Medicine
Natural Sciences in General
Physics
|
| Keywords: |
Biochemistry, Botany
|
| Published by: |
| _version_ | 1836398973549543424 |
|---|---|
| autor | Caputi, L., Franke, J., Farrow, S. C., Chung, K., Payne, R. M. E., Nguyen, T.-D., Dang, T.-T. T., Soares Teto Carqueijeiro, I., Koudounas, K., Duge de Bernonville, T., Ameyaw, B., Jones, D. M., Vieira, I. J. C., Courdavault, V., OConnor, S. E. |
| beschreibung | Vinblastine, a potent anticancer drug, is produced by Catharanthus roseus (Madagascar periwinkle) in small quantities, and heterologous reconstitution of vinblastine biosynthesis could provide an additional source of this drug. However, the chemistry underlying vinblastine synthesis makes identification of the biosynthetic genes challenging. Here we identify the two missing enzymes necessary for vinblastine biosynthesis in this plant: an oxidase and a reductase that isomerize stemmadenine acetate into dihydroprecondylocarpine acetate, which is then deacetoxylated and cyclized to either catharanthine or tabersonine via two hydrolases characterized herein. The pathways show how plants create chemical diversity and also enable development of heterologous platforms for generation of stemmadenine-derived bioactive compounds. |
| citation_standardnr | 6284037 |
| datenlieferant | ipn_articles |
| feed_id | 25 |
| feed_publisher | American Association for the Advancement of Science (AAAS) |
| feed_publisher_url | http://www.aaas.org/ |
| insertion_date | 2018-06-15 |
| journaleissn | 1095-9203 |
| journalissn | 0036-8075 |
| publikationsjahr_anzeige | 2018 |
| publikationsjahr_facette | 2018 |
| publikationsjahr_intervall | 7984:2015-2019 |
| publikationsjahr_sort | 2018 |
| publisher | American Association for the Advancement of Science (AAAS) |
| quelle | Science |
| relation | http://science.sciencemag.org/cgi/content/short/360/6394/1235?rss=1 |
| schlagwort | Biochemistry, Botany |
| search_space | articles |
| shingle_author_1 | Caputi, L., Franke, J., Farrow, S. C., Chung, K., Payne, R. M. E., Nguyen, T.-D., Dang, T.-T. T., Soares Teto Carqueijeiro, I., Koudounas, K., Duge de Bernonville, T., Ameyaw, B., Jones, D. M., Vieira, I. J. C., Courdavault, V., OConnor, S. E. |
| shingle_author_2 | Caputi, L., Franke, J., Farrow, S. C., Chung, K., Payne, R. M. E., Nguyen, T.-D., Dang, T.-T. T., Soares Teto Carqueijeiro, I., Koudounas, K., Duge de Bernonville, T., Ameyaw, B., Jones, D. M., Vieira, I. J. C., Courdavault, V., OConnor, S. E. |
| shingle_author_3 | Caputi, L., Franke, J., Farrow, S. C., Chung, K., Payne, R. M. E., Nguyen, T.-D., Dang, T.-T. T., Soares Teto Carqueijeiro, I., Koudounas, K., Duge de Bernonville, T., Ameyaw, B., Jones, D. M., Vieira, I. J. C., Courdavault, V., OConnor, S. E. |
| shingle_author_4 | Caputi, L., Franke, J., Farrow, S. C., Chung, K., Payne, R. M. E., Nguyen, T.-D., Dang, T.-T. T., Soares Teto Carqueijeiro, I., Koudounas, K., Duge de Bernonville, T., Ameyaw, B., Jones, D. M., Vieira, I. J. C., Courdavault, V., OConnor, S. E. |
| shingle_catch_all_1 | Missing enzymes in the biosynthesis of the anticancer drug vinblastine in Madagascar periwinkle Biochemistry, Botany Vinblastine, a potent anticancer drug, is produced by Catharanthus roseus (Madagascar periwinkle) in small quantities, and heterologous reconstitution of vinblastine biosynthesis could provide an additional source of this drug. However, the chemistry underlying vinblastine synthesis makes identification of the biosynthetic genes challenging. Here we identify the two missing enzymes necessary for vinblastine biosynthesis in this plant: an oxidase and a reductase that isomerize stemmadenine acetate into dihydroprecondylocarpine acetate, which is then deacetoxylated and cyclized to either catharanthine or tabersonine via two hydrolases characterized herein. The pathways show how plants create chemical diversity and also enable development of heterologous platforms for generation of stemmadenine-derived bioactive compounds. Caputi, L., Franke, J., Farrow, S. C., Chung, K., Payne, R. M. E., Nguyen, T.-D., Dang, T.-T. T., Soares Teto Carqueijeiro, I., Koudounas, K., Duge de Bernonville, T., Ameyaw, B., Jones, D. M., Vieira, I. J. C., Courdavault, V., OConnor, S. E. American Association for the Advancement of Science (AAAS) 0036-8075 00368075 1095-9203 10959203 |
| shingle_catch_all_2 | Missing enzymes in the biosynthesis of the anticancer drug vinblastine in Madagascar periwinkle Biochemistry, Botany Vinblastine, a potent anticancer drug, is produced by Catharanthus roseus (Madagascar periwinkle) in small quantities, and heterologous reconstitution of vinblastine biosynthesis could provide an additional source of this drug. However, the chemistry underlying vinblastine synthesis makes identification of the biosynthetic genes challenging. Here we identify the two missing enzymes necessary for vinblastine biosynthesis in this plant: an oxidase and a reductase that isomerize stemmadenine acetate into dihydroprecondylocarpine acetate, which is then deacetoxylated and cyclized to either catharanthine or tabersonine via two hydrolases characterized herein. The pathways show how plants create chemical diversity and also enable development of heterologous platforms for generation of stemmadenine-derived bioactive compounds. Caputi, L., Franke, J., Farrow, S. C., Chung, K., Payne, R. M. E., Nguyen, T.-D., Dang, T.-T. T., Soares Teto Carqueijeiro, I., Koudounas, K., Duge de Bernonville, T., Ameyaw, B., Jones, D. M., Vieira, I. J. C., Courdavault, V., OConnor, S. E. American Association for the Advancement of Science (AAAS) 0036-8075 00368075 1095-9203 10959203 |
| shingle_catch_all_3 | Missing enzymes in the biosynthesis of the anticancer drug vinblastine in Madagascar periwinkle Biochemistry, Botany Vinblastine, a potent anticancer drug, is produced by Catharanthus roseus (Madagascar periwinkle) in small quantities, and heterologous reconstitution of vinblastine biosynthesis could provide an additional source of this drug. However, the chemistry underlying vinblastine synthesis makes identification of the biosynthetic genes challenging. Here we identify the two missing enzymes necessary for vinblastine biosynthesis in this plant: an oxidase and a reductase that isomerize stemmadenine acetate into dihydroprecondylocarpine acetate, which is then deacetoxylated and cyclized to either catharanthine or tabersonine via two hydrolases characterized herein. The pathways show how plants create chemical diversity and also enable development of heterologous platforms for generation of stemmadenine-derived bioactive compounds. Caputi, L., Franke, J., Farrow, S. C., Chung, K., Payne, R. M. E., Nguyen, T.-D., Dang, T.-T. T., Soares Teto Carqueijeiro, I., Koudounas, K., Duge de Bernonville, T., Ameyaw, B., Jones, D. M., Vieira, I. J. C., Courdavault, V., OConnor, S. E. American Association for the Advancement of Science (AAAS) 0036-8075 00368075 1095-9203 10959203 |
| shingle_catch_all_4 | Missing enzymes in the biosynthesis of the anticancer drug vinblastine in Madagascar periwinkle Biochemistry, Botany Vinblastine, a potent anticancer drug, is produced by Catharanthus roseus (Madagascar periwinkle) in small quantities, and heterologous reconstitution of vinblastine biosynthesis could provide an additional source of this drug. However, the chemistry underlying vinblastine synthesis makes identification of the biosynthetic genes challenging. Here we identify the two missing enzymes necessary for vinblastine biosynthesis in this plant: an oxidase and a reductase that isomerize stemmadenine acetate into dihydroprecondylocarpine acetate, which is then deacetoxylated and cyclized to either catharanthine or tabersonine via two hydrolases characterized herein. The pathways show how plants create chemical diversity and also enable development of heterologous platforms for generation of stemmadenine-derived bioactive compounds. Caputi, L., Franke, J., Farrow, S. C., Chung, K., Payne, R. M. E., Nguyen, T.-D., Dang, T.-T. T., Soares Teto Carqueijeiro, I., Koudounas, K., Duge de Bernonville, T., Ameyaw, B., Jones, D. M., Vieira, I. J. C., Courdavault, V., OConnor, S. E. American Association for the Advancement of Science (AAAS) 0036-8075 00368075 1095-9203 10959203 |
| shingle_title_1 | Missing enzymes in the biosynthesis of the anticancer drug vinblastine in Madagascar periwinkle |
| shingle_title_2 | Missing enzymes in the biosynthesis of the anticancer drug vinblastine in Madagascar periwinkle |
| shingle_title_3 | Missing enzymes in the biosynthesis of the anticancer drug vinblastine in Madagascar periwinkle |
| shingle_title_4 | Missing enzymes in the biosynthesis of the anticancer drug vinblastine in Madagascar periwinkle |
| timestamp | 2025-06-30T23:35:34.480Z |
| titel | Missing enzymes in the biosynthesis of the anticancer drug vinblastine in Madagascar periwinkle |
| titel_suche | Missing enzymes in the biosynthesis of the anticancer drug vinblastine in Madagascar periwinkle |
| topic | W V TE-TZ SQ-SU WW-YZ TA-TD U |
| uid | ipn_articles_6284037 |