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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-EPMC4471609 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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

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

Angewandte Chemie (International ed. in English) 20150225 17

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 chanocl ...[more]

PMID: 25712404

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