期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 54, 期 17, 页码 5117-5121出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201410002
关键词
biosynthesis; cyclopropyl group; ergot alkaloids; natural products; pathway reconstitution
资金
- BBSRC [BB/J018171/1]
- BBSRC [BB/J018171/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/J018171/1] Funding Source: researchfish
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.
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