Discovery and Reconstitution of the Cycloclavine Biosynthetic Pathway-Enzymatic Formation of a Cyclopropyl Group.
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 mg L-1, thus demonstrating the feasibility of the heterologous expression of these complex alkaloids.
['Jakubczyk|Dorota|D|', 'Caputi|Lorenzo|L|', 'Hatsch|Anaëlle|A|', 'Nielsen|Curt A F|CA|', 'Diefenbacher|Melanie|M|', 'Klein|Jens|J|', 'Molt|Andrea|A|', 'Schröder|Hartwig|H|', 'Cheng|Johnathan Z|JZ|', 'Naesby|Michael|M|', "O'Connor|Sarah E|SE|"]
Biosynthese Cyclopropane Mutterkornalkaloide Naturstoffe Rekonstitution