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Discovery and Reconstitution of the Cycloclavine Biosynthetic Pathway—Enzymatic Formation of a Cyclopropyl Group
Author(s) -
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.
Publication year - 2015
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201410002
Subject(s) - moiety , enzyme , stereochemistry , heterologous expression , heterologous , yeast , biosynthesis , biochemistry , chemistry , in vitro , biology , recombinant dna , gene
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.