Results
Title

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

Authors

Chen, Yue‐Gui; Li, De‐Sen; Ling, Yi; Liu, Yan‐Chun; Zuo, Zhi‐Li; Gan, Li‐She; Luo, Shi‐Hong; Hua, Juan; Chen, Ding‐Yuan; Xu, Fan; Li, Man; Guo, Kai; Liu, Yan; Gershenzon, Jonathan; Li, Sheng‐Hong

Abstract

A versatile terpene synthase (LcTPS2) producing unconventional macrocyclic terpenoids was characterized from Leucosceptrum canum. Engineered Escherichia coli and Nicotiana benthamiana expressing LcTPS2 produced six 18‐/14‐membered sesterterpenoids including five new ones and two 14‐membered diterpenoids. These products represent the first macrocyclic sesterterpenoids from plants and the largest sesterterpenoid ring system identified to date. Two variants F516A and F516G producing approximately 3.3‐ and 2.5‐fold, respectively, more sesterterpenoids than the wild‐type enzyme were engineered. Both 18‐ and 14‐membered ring sesterterpenoids displayed significant inhibitory activity on the IL‐2 and IFN‐γ production of T cells probably via inhibition of the 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.

Subjects

TERPENES; DITERPENES; T cells; NICOTIANA benthamiana; ENZYMES; ESCHERICHIA coli

Publication

Angewandte Chemie, 2021, Vol 133, Issue 48, p25672

ISSN

0044-8249

Publication type

Academic Journal

DOI

10.1002/ange.202110842