Substrate promiscuity of enzymes from the sesquiterpene biosynthetic pathways from Artemisia annua and Tanacetum parthenium allows for novel combinatorial sesquiterpene production.

The therapeutic properties of complex terpenes often depend on the stereochemistry of their functional groups. However, stereospecific chemical synthesis of terpenes is challenging. To overcome this challenge, metabolic engineering can be employed using enzymes with suitable stereospecific catalytic activity. Here we used a combinatorial metabolic engineering approach to explore the stereospecific modification activity of the Artemisia annua artemisinic aldehyde ∆11(13) double bond reductase2 (AaDBR2) on products of the feverfew sesquiterpene biosynthesis pathway (GAS, GAO, COS and PTS). This allowed us to produce dihydrocostunolide and dihydroparthenolide. For dihydroparthenolide we demonstrate that the preferred order of biosynthesis of dihydroparthenolide is by reduction of the exocyclic methylene of parthenolide, rather than through C4-C5 epoxidation of dihydrocostunolide. Moreover, we demonstrate a promiscuous activity of feverfew CYP71CB1 on dihydrocostunolide and dihydroparthenolide for the production of 3ß-hydroxy-dihydrocostunolide and 3ß-hydroxy-dihydroparthenolide, respectively. Combined, these results offer new opportunities for engineering novel sesquiterpene lactones with potentially improved medicinal value.

Studies on bioactive constituents in bark of Tsoongiodendron odorum / 中草药

Object To study the chemical constituent and the bioactivity in the bark of Tsoongiodendron odorum Chun Methods By bioactive following method, the extracts of both EtOAc and n BuOH in the bark of T odorum were screened for in vitro anti tumor activity Results Five constituents were obtained Among them, three from EtOAc fraction belonged to germacranolides They were costunolide (Ⅰ), parthenolide (Ⅱ) and dihydroparthenolide (Ⅲ) The other two were from the fraction of n BuOH, one was an oxoaporphinoid alkaloid, liriodenine (Ⅳ), and the last was a furanone, 2, 3 dihydroxyl 2 methyl butylrolactone (Ⅴ) Conclusion All the above five compounds are found for the first time from this plant Compounds Ⅰ, Ⅱ, Ⅳ, and Ⅴ show the cytotoxic activities against a variety of tumor cell strains, respectively