A collaborative research between two teams led by Dr. Hsiao-Ching Lin, an assistant research fellow at the Institute of Biological Chemistry, and Dr. Rong-Jie Chein, an associate research fellow at the Institute of Chemistry, has identified the biosynthetic gene cluster and characterized two crucial enzymes in the biosynthesis of asperpentyn. This work opens up opportunities for the generation of 1,3-enynes using enzymatic approaches and was recently published in Angewandte Chemie International Edition.
Enynes are an important functionality in organic chemistry due to their broad applications in organic synthesis, functional materials, and medicinal chemistry. Although many synthetic strategies have been developed to construct 1,3-enynes, little is known about the way nature generates this motif.
The Lin’s group report the identification of the asperpentyn (aty) biosynthetic gene cluster from Aspergillus sp. PSU-RSPG185. They discovered a unique P450 monooxygenase that has a dual function to first catalyze dehydrogenation of the prenyl chain to generate a cis-diene intermediate and then shows acetylenase activity to yield an alkyne moiety, giving the 1,3-enyne. The catalytic mechanism has also been characterized by using a series of substrate analogs and intermediate mimics. They also characterized an unusual UbiA prenyltransferase, that installs a short (C5) prenyl chain to a p-hydroxybenzoic acid acceptor. The studies were performed with the combination of the Saccharomyces cerevisiae heterologous expression system, in vitro enzymatic assays and synthesized substrate analogs. Collectively, these results not only provide critical new insights into the biosynthesis of fungal cyclohexanoid terpenoids, but also offer a potential route for the de novo biosynthesis of terpenoids with a 1,3-enyne functionality.
Article title: “Discovery of a Dual Function Cytochrome P450 that Catalyzes Enyne Formation in Cyclohexanoid Terpenoid Biosynthesis”
Article link: https://doi.org/10.1002/anie.202004435