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A Cryptic Plant Terpene Cyclase Producing Unconventional 18- and 14-Membered Macrocyclic C 25 and C 20 Terpenoids with Immunosuppressive Activity.
- Source :
-
Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2021 Nov 22; Vol. 60 (48), pp. 25468-25476. Date of Electronic Publication: 2021 Oct 28. - Publication Year :
- 2021
-
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.<br /> (© 2021 Wiley-VCH GmbH.)
- Subjects :
- Humans
Immunosuppressive Agents chemistry
Immunosuppressive Agents metabolism
Interferon-gamma biosynthesis
Interleukin-2 biosynthesis
Lamiaceae chemistry
Lamiaceae metabolism
Macrocyclic Compounds chemistry
Macrocyclic Compounds metabolism
Molecular Structure
T-Lymphocytes drug effects
T-Lymphocytes metabolism
Terpenes chemistry
Terpenes metabolism
Alkyl and Aryl Transferases metabolism
Immunosuppressive Agents pharmacology
Interferon-gamma antagonists & inhibitors
Interleukin-2 antagonists & inhibitors
Macrocyclic Compounds pharmacology
Terpenes pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1521-3773
- Volume :
- 60
- Issue :
- 48
- Database :
- MEDLINE
- Journal :
- Angewandte Chemie (International ed. in English)
- Publication Type :
- Academic Journal
- Accession number :
- 34580976
- Full Text :
- https://doi.org/10.1002/anie.202110842