Discovery and Reconstitution of the Cycloclavine Biosynthetic Pathway—Enzymatic Formation of a Cyclopropyl Group1. (25th February 2015)

• Record Type: Journal Article
• Authors: Jakubczyk, Dorota; Caputi, Lorenzo; Hatsch, Anaëlle; Nielsen, Curt A. F.; Diefenbacher, Melanie; Klein, Jens; Molt, Andrea; Schröder, Hartwig; Cheng, Johnathan Z.; Naesby, Michael; O'Connor, Sarah E.
• Is Part Of: Angewandte Chemie. Volume 127:Number 17(2015)
• Page Start: 5206
• Page End: 5210
• Publication Date: 2015-02-25
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201410002
• Languages: English
• ISSNs: 0044-8249

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>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 &gt;500 mg L⁻¹, thus demonstrating the feasibility of the heterologous expression of these complex alkaloids.</p> </abstract>