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

Publisher: John Wiley & Sons Inc

E-ISSN: 1521-3757|127|17|5206-5210

ISSN: 0044-8249

Source: ANGEWANDTE CHEMIE, Vol.127, Iss.17, 2015-04, pp. : 5206-5210

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Abstract

AbstractThe 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.