Discovery and reconstitution of the cycloclavine biosynthetic pathwa—enzymatic 
formation of a cyclopropyl group

Jakubczyk, Dorota; Caputi, Lorenzo; Hatsch, Anaelle; Nielsen, Curt A. F.; Diefenbacher, Melanie; Klein, Jens; Molt, Andrea; Schroeder, Hartwig; Cheng, Johnathan Z.; Naesby, Michael; O'Connor, Sarah E.

doi:10.1002/anie.201410002

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Discovery and reconstitution of the cycloclavine biosynthetic pathwa—enzymatic formation of a cyclopropyl group

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4471609/
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Jakubczyk, D., Caputi, L., Hatsch, A., Nielsen, C. A. F., Diefenbacher, M., Klein, J., et al. (2015). Discovery and reconstitution of the cycloclavine biosynthetic pathwa—enzymatic formation of a cyclopropyl group. Angewandte Chemie International Edition, 54(17), 5117-5121. doi:10.1002/anie.201410002.

Cite as: https://hdl.handle.net/21.11116/0000-0002-B6F9-8

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 mgL(-1), thus demonstrating the feasibility of the heterologous expression of these complex alkaloids.