Missing enzymes in the biosynthesis of the anticancer drug vinblastine in Madagascar periwinkle

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
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SQ-SU
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uid ipn_articles_6284037