ausblenden:
Schlagwörter:
OLD YELLOW ENZYME; ERGOT ALKALOID BIOSYNTHESIS; ASPERGILLUS-FUMIGATUS; LYSERGIC-ACID; BRANCH POINT; (+/-)-CYCLOCLAVINE; JAPONICUS; EXPRESSION;
FAMILYChemistry; biosynthesis; cyclopropyl group; ergot alkaloids; natural products;
pathway reconstitution;
Zusammenfassung:
The ergot alkaloids, a class of fungal-derived natural products with important biological activities, are derived from a common intermediate, chanoclavine-I, which is elaborated into a set of diverse structures. Herein we report the discovery of the biosynthetic pathway of cycloclavine, a complex ergot alkaloid containing a cyclopropyl moiety. We used a yeast-based expression platform along with in vitro biochemical experiments to identify the enzyme that catalyzes a rearrangement of the chanoclavine-I intermediate to form a cyclopropyl moiety. The resulting compound, cycloclavine, was produced in yeast at titers of >500 mgL(-1), thus demonstrating the feasibility of the heterologous expression of these complex alkaloids.
