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Updated: Oct 26, 2026
A Customizable Approach for the Enzymatic Production and Purification of Diterpenoid Natural Products
Published on: October 4, 2019
Targeted Discovery of Unknown Eremophilane Sesquiterpenes Guided by the Characteristic Post-Modification
Qinglin Zhang1, Zian Wang1, Huixue Ma1
1School of Medicine and Pharmacy, Key Laboratory of Marine Drugs Ministry of Education, Sanya Oceanographic Institute, Frontiers Science Center for Deep Ocean Multispheres and Earth System, Ocean University of China, Qingdao266000, P. R. China.
Abstract:
PR-toxin and Sporogen-AO1 have garnered widespread interest, and their structural divergence is attributed to two distinctive sets of tailoring enzymes. Despite recent elucidation of their respective biosynthetic pathways, these two distinctive tailoring cassettes can only operate independently within natural hosts. Based on the Characteristic Post-Modification Colocalization genome mining strategy, this study reports the first discovery of a new class of biosynthetic gene clusters with merged characteristic post-modifications. Furthermore, heterologous expression of pbe gene cluster, led to the production of seven new eremophilane-type sesquiterpenoids (1-7). Notably, compound 1 represents the first occurring eremophilane-type sesquiterpene bearing both 1,2-epoxy and 6,7-epoxy moieties. In bioassays, compounds 3 and 8 exhibited significant cytotoxicity against the K562 cell line, with IC50 values of 10.93 μM and 1.03 μM, respectively. Taken together, this research offers an innovative method for the directed discovery of natural products.
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