Oxidation and cyclization of Casbene in the biosynthesis of Euphorbia factors from mature seeds of Euphorbia lathyris L
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Oxidation and cyclization of Casbene in the biosynthesis of Euphorbia factors from mature seeds of Euphorbia lathyris L. / Luo, Dan; Callari, Roberta; Hamberger, Britta; Wubshet, Sileshi Gizachew; Nielsen, Morten Thrane; Andersen-Ranberg, Johan; Hallström, Björn M; Cozzi, Federico; Heider, Harald; Møller, Birger Lindberg; Stærk, Dan; Hamberger, Björn Robert.
I: Proceedings of the National Academy of Sciences of the United States of America, Bind 113, Nr. 34, 2016, s. E5082-E5089.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Oxidation and cyclization of Casbene in the biosynthesis of Euphorbia factors from mature seeds of Euphorbia lathyris L
AU - Luo, Dan
AU - Callari, Roberta
AU - Hamberger, Britta
AU - Wubshet, Sileshi Gizachew
AU - Nielsen, Morten Thrane
AU - Andersen-Ranberg, Johan
AU - Hallström, Björn M
AU - Cozzi, Federico
AU - Heider, Harald
AU - Møller, Birger Lindberg
AU - Stærk, Dan
AU - Hamberger, Björn Robert
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
U2 - 10.1073/pnas.1607504113
DO - 10.1073/pnas.1607504113
M3 - Journal article
C2 - 27506796
VL - 113
SP - E5082-E5089
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 34
ER -
ID: 167358273