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Discovery and Reconstitution of the Cycloclavine Biosynthetic Pathway-Enzymatic Formation of a Cyclopropyl Group.

ABSTRACT: 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.

SUBMITTER: Jakubczyk D

PROVIDER: S-EPMC4974921 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Discovery and reconstitution of the cycloclavine biosynthetic pathway--enzymatic formation of a cyclopropyl group.

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