Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 53, Issue 11, Pages 3011-3014Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201310641
Keywords
biosynthesis; heterologous expression; ikarugamycin; natural products; PTMs
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Funding
- Fonds der Chemischen Industrie (FCI)
- North Rhine-Westphalian Academy of Scienes, Humanities and the Arts (Junges Kolleg)
- DFG [GU1233/2-1]
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Polycyclic tetramate macrolactams (PTMs) are a family of biomedically promising natural products with challenging molecular frameworks. Despite these interesting properties, so far only relatively little is known about the biosynthetic origin of PTMs, in particular concerning the mechanism by which their ring systems are formed. Herein we present the first insights into these processes by using the biosynthesis of ikarugamycin as an example. This has been facilitated by the first heterologous expression of a PTM biosynthetic gene cluster in Escherichia coli. With this approach it will not only become possible to mechanistically investigate already known PTM biosynthetic pathways in more detail in the future, but also to interrogate cryptic PTM biosynthetic pathways chemically and biochemically.
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