title: Heterologous reconstitution of ikarugamycin biosynthesis in E. coli.
abstract: 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.
authors: Kekulé-Institut für Organische Chemie und Biochemie, Universität Bonn, Gerhard-Domagk-Strasse 1 (Germany); Department Chemie, Technische Universität München, Lichtenbergstrasse 4, 85748 Garching (Germany) http://www.biosystemchemie.ch.tum.de.
authors: Janine
authors: J
authors: Antosch
authors: Françoise
authors: F
authors: Schaefers
authors: Tobias A M
authors: TA
authors: Gulder
mesh_terms: D001688:Biological Products / Q000737:chemistry / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D007769:Lactams / Q000737:chemistry / Q000378:metabolism*; D005810:Multigene Family; D010453:Peptide Synthases / Q000235:genetics; D048630:Polyketide Synthases / Q000235:genetics
chemical_list: D001688:Biological Products; D007769:Lactams; C074292:ikarugamycin; D048630:Polyketide Synthases; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase
keywords: PTMs; biosynthesis; heterologous expression; ikarugamycin; natural products