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Heterologous Reconstitution of Ikarugamycin Biosynthesis in E. coli
Author(s) -
Antosch Janine,
Schaefers Françoise,
Gulder Tobias A. M.
Publication year - 2014
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.201310641
Subject(s) - biosynthesis , heterologous expression , gene cluster , heterologous , escherichia coli , computational biology , mechanism (biology) , gene , biology , biochemistry , chemistry , recombinant dna , philosophy , epistemology
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.