Stanford University | Chemistry Department | Events | Conferences and Lectures

Conferences & Lectures :
24th Annual William S. Johnson Symposium

W.S. Johnson Speaker:
Mohamed Marahiel

Philipps University of Marburg

About Marahiel:
M. A. Marahiel studied chemistry at the Universities of Cairo (Egypt) and Göttingen (Germany). In 1977, he obtained a PhD in biochemistry and microbiology from the University of Göttingen. Subsequently, he received an assistant professor's position at the Technical University of Berlin, where in 1987 he obtained his Habilitation in biochemistry. Three years later he moved to the Philipps-Universität as a professor of biochemistry in the chemistry department. He was a DFG fellow in 1978 and 1986 at the John Innes Institute in Norwich (UK) and at the Biolabs, Harvard University (USA), respectively. Since 2004 he is a member of the "Leopoldina" - Deutsche Akademie der Naturforscher and since 2009 a fellow of The Royal Society of Chemistry. His present research focuses on the structure-function relationship and on the elucidation of reaction mechanisms of modular peptide synthetases involved in the nonribosomal synthesis of peptide antibiotics. His group is also interested in studying ribosomally synthesized peptide antibiotics, siderophores and stress-induced proteins in Bacteria.

Marahiel's lecture at the Johnson Symposium:
"The Molecular Logic of an NRPS Assembly Line"

A widespread class of therapeutically important natural products are of peptide origin. They are produced by large “assembly line” multienzyme complexes, the nonribosomal peptide synthetases (NRPS). Crystal and NMR structures of individual NRPS domains associated with substrate selection and activation (A-domain), substrate shuttling among the active sites (PCP-domain) and building block condensation (C-domain) into the growing peptide chain provided important insights into molecular and dynamic aspects of the catalytic mechanisms. [1,2]. NMR spectroscopic studies revealed alternative conformational states for the substrate carrier domains (PCP) and suggested a critical role for these conformational switches in the specific domain-domain interaction and partner protein recognition during the NRPS assembly line synthesis [3]. However, this structural knowledge on individual catalytic units can not provide information on how individual catalytic domains are oriented and connected in relationship to each other in the three-dimensional structure of an intact NRPS module. This information is a key for our understanding on how the covalently bound substrates are correctly shuttled in time and space between the catalytic centers and how the domain’s movement is coordinated. The recent elucidation of the crystal structure of the entire termination module SrfA-C (C-A-PCP-TE) from the surfactin synthetase [4] is an important contribution towards understanding the molecular logic that govern such multi-modular megaenzymes and also provided few lessens concerning attempts to rationally manipulate NRPS.

[1] Finking, R., and Marahiel, M. A. (2004). Biosynthesis of nonribosomal peptides. Annu. Rev. Microbiol. 58, 453-488
[2] Samel, S. A., Schönafinger, G., Knappe, T. A., Marahiel, M. A., and Essen, L.-O. (2007). Structural and functional
insights into a peptide bond-forming bidomain from a nonribosomal peptide synthetase. Structure 15, 781-792.
[3] Koglin, A., Mofid, M. R., Löhr, F., Schäfer, B., Rogov, V. V., Blum, M.-M., Mittag, T., Marahiel, M.A., Bernhard, F.,
and Dötsch, V. (2006). Conformational switches modulate protein interactions in peptide antibiotic synthetases. Science 312, 273-276.
[4] Tanovic, A., Samel, S. A., Essen, L.-O., and Marahiel, M. A. (2008). Crystal structure of the termination module of a nonribosomal peptide synthetase. Science 32, 659-663.

Questions:
If you have questions or need additional information please contact Patricia Dwyer at 650-723-4770