Identification of a Noroxomaritidine Reductase with Amaryllidaceae Alkaloid Biosynthesis Related Activities.
| Autor: | Kilgore MB; From the Donald Danforth Plant Science Center, St. Louis, Missouri 63132 and the Department of Biology, Washington University in St. Louis, St. Louis, Missouri 63130., Holland CK; the Department of Biology, Washington University in St. Louis, St. Louis, Missouri 63130., Jez JM; the Department of Biology, Washington University in St. Louis, St. Louis, Missouri 63130., Kutchan TM; From the Donald Danforth Plant Science Center, St. Louis, Missouri 63132 and tmkutchan@danforthcenter.org. |
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| Jazyk: | angličtina |
| Zdroj: | The Journal of biological chemistry [J Biol Chem] 2016 Aug 05; Vol. 291 (32), pp. 16740-52. Date of Electronic Publication: 2016 Jun 01. |
| DOI: | 10.1074/jbc.M116.717827 |
| Abstrakt: | Amaryllidaceae alkaloids are a large group of plant natural products with over 300 documented structures and diverse biological activities. Several groups of Amaryllidaceae alkaloids including the hemanthamine- and crinine-type alkaloids show promise as anticancer agents. Two reduction reactions are required for the production of these compounds: the reduction of norcraugsodine to norbelladine and the reduction of noroxomaritidine to normaritidine, with the enantiomer of noroxomaritidine dictating whether the derivatives will be the crinine-type or hemanthamine-type. It is also possible for the carbon-carbon double bond of noroxomaritidine to be reduced, forming the precursor for maritinamine or elwesine depending on the enantiomer reduced to an oxomaritinamine product. In this study, a short chain alcohol dehydrogenase/reductase that co-expresses with the previously discovered norbelladine 4'-O-methyltransferase from Narcissus sp. and Galanthus spp. was cloned and expressed in Escherichia coli Biochemical analyses and x-ray crystallography indicates that this protein functions as a noroxomaritidine reductase that forms oxomaritinamine from noroxomaritidine through a carbon-carbon double bond reduction. The enzyme also reduces norcraugsodine to norbelladine with a 400-fold lower specific activity. These studies identify a missing step in the biosynthesis of this pharmacologically important class of plant natural products. (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.) |
| Databáze: | MEDLINE |
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