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Published Online June 26, 2008
Science DOI: 10.1126/science.1159850

Research Articles

Submitted on April 30, 2008
Accepted on June 16, 2008

Crystal Structure of the Termination Module of a Nonribosomal Peptide Synthetase

Alan Tanovic 1, Stefan A. Samel 1, Lars-Oliver Essen 1*, Mohamed A. Marahiel 1*

1 Biochemistry, Department of Chemistry, Philipps University Marburg, Hans-Meerwein-Strasse, D35032 Marburg, Germany.

* To whom correspondence should be addressed.
Lars-Oliver Essen , E-mail: essen{at}chemie.uni-marburg.de
Mohamed A. Marahiel , E-mail: marahiel{at}chemie.uni-marburg.de

Nonribosomal peptide synthetases (NRPS) are modularly organized megaenzymes that act as an assembly line to catalyze the biosynthesis of complex natural products. The crystal structure of the 144 kD termination module SrfA-C that comprises four essential domains was solved at 2.6 Å resolution. Its architecture shows that the adenylation and condensation domains associate closely to form a catalytic platform with their active sites on the same side of the platform. The peptidyl-carrier domain is flexibly tethered to this platform and thus able to move with its substrate-loaded 4-phosphopantetheine arm between the active site of the adenylation domain and the donor side of the condensation domain. Furthermore, the SrfA-C crystal structure inspires further investigations on rational redesign of NRPS for production of novel bioactive peptides.


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Science. ISSN 0036-8075 (print), 1095-9203 (online)