Oxidation and cyclization of Casbene in the biosynthesis of Euphorbia factors from mature seeds of Euphorbia lathyris L
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Ingenol mebutate is a diterpene ester with a highly complex macrocyclic structure that has been approved for the treatment of actinic keratosis, a precondition of skin cancer. The current production of ingenol mebutate through plant extraction or chemical synthesis is inefficient and costly. Here, we describe the discovery of a biosynthetic route in Euphorbia lathyris L. (caper spurge) in which regio-specific oxidation of casbene is followed by an unconventional cyclization to yield jolkinol C, a probable key intermediate in the biosynthesis of macrocyclic diterpenes, including ingenol mebutate. These results can facilitate the biotechnological production of this high-value pharmaceutical and discovery of new biosynthetic intermediates with important bioactivities.
Original language | English |
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Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 113 |
Issue number | 34 |
Pages (from-to) | E5082-E5089 |
Number of pages | 8 |
ISSN | 0027-8424 |
DOIs | |
Publication status | Published - 2016 |
ID: 167358273