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.
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Introduction to Sheng-Hong Li
Sheng-Hong Li received his PhD Degree in Phytochemistry from Kunming Institute of Botany, Chinese Academy of Sciences in 2001. After that he worked as an Assistant Professor and then Associate Professor at the same institute. In 2004, he moved to the Max Planck Institute for Chemical Ecology in Germany for his postdoctoral research with Prof. Jonathan Gershenzon and Dr Bernd Schneider. From 2007 to 2020, he was employed as a Full Professor and group leader by Kunming Institute of Botany, Chinese Academy of Sciences. Currently he is Vice President of Chengdu University of Traditional Chinese Medicine. He received the Alexander von Humboldt Research Fellowship in 2005 and National Science Fund for Distinguished Young Scholars in 2015 and was selected as a member of the National Ten Thousand Talent Program (2018), and the Hundred Talent Program of Chinese Academy of Sciences (2010). He has published over 120 research papers. His major research interests focus on the chemistry, biological functions and biosynthesis of plant natural products especially various types of terpenoids.