A Cryptic Plant Terpene Cyclase Producing Unconventional 18‐ and 14‐Membered Macrocyclic C 25 and C 20 Terpenoids with Immunosuppressive Activity

Autor: Yue-Gui Chen, Kai Guo, Man Li, Juan Hua, Zhi-Li Zuo, Sheng-Hong Li, Jonathan Gershenzon, Shi-Hong Luo, De-Sen Li, Ding-Yuan Chen, Li-She Gan, Fan Xu, Yi Ling, Yan-Chun Liu, Yan Liu
Rok vydání: 2021
Předmět:
Zdroj: Angewandte Chemie International Edition. 60:25468-25476
ISSN: 1521-3773
1433-7851
DOI: 10.1002/anie.202110842
Popis: A versatile terpene synthase (LcTPS2) producing unconventional macrocyclic terpenoids was characterized from Leucosceptrum canum. Engineered E. coli and Nicotiana benthamiana expressing LcTPS2 produced six 18-/14-membered sesterterpenoids including five new ones and two 14-membered diterpenoids, representing the first macrocyclic sesterterpenoids from plants and the largest sesterterpenoid ring system identified to date. Surprisingly, none of these macrocyclic terpenoids were detected in L. canum. Two variants F516A and F516G producing approximately 3.3- and 2.5- folds respectively more sesterterpenoids than the wild type enzyme was engineered. Both 18- and 14-membered ring sesterterpenoids displayed significant inhibitory activity on the IL-2 and IFN-I³ production of T cells via inhibition of MAPK pathway. The findings will contribute to the development of efficient biocatalysts to create bioactive macrocyclic sesterterpenoids, and also herald a new potential in the well-trodden territory of plant terpenoid biosynthesis.
Databáze: OpenAIRE
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