Table of Contents:
Nonribosomal peptide synthetases (NRPSs) utilize complex regiospecific and stereospecific reactions to assemble structurally and functionally diverse peptides. Despite the large number of their components and the great diversity of products, the NRPS systems hold a close structural relationship. The NRPS systems shows a modular organisation with defined domains which catalyzing the single reactions. In addition to the catalytic domains the role of dynamic peptidyl carrier protein (PCP) is crucial for understanding of the NRPS mode of action. In this work the disruption of the PCP dynamic via serine to alanin variation or attached pantotheine derivatives and whose effect on the global structure was investigated. Freezing the PCP domain in the AH state allowed the structure determination of a complete termination module of the surfactin synthetase. This structure model shows various unique properties, describing the domain interactions between the condensation domain and PCP, the first DC L domain structure model, an artificial COM helix � COM hand motif as well as a novel orientation of the adenylation subdomain relating to the adenylation coredomain. Furthermore, the formation of a close interaction between the condensation and the two subdomains of the adenylation domain (Acore and Asub), which is called the workbench be noted. Subsequent studies using small-angle scattering (SAXS) showed that this close interaction persists even in the solvated state. This studies confirm the important role of the workbench as a model system for the general understanding of NRPS systems. By combining the structural data of the bidomain structure of TycC5-6 with the surfactin termination module SrfAC a multimodulare NRPS model can be created. This model shows a counter clockwise screw axis where each module along the assembly line ist rotated by 120� as well the complete structural model of the different linker regions. The knowledge about the NRPS organization increase the possibility of constructing active chimeric enzymes, where intact modules or even single domains are exchanged to allow the biosynthesis of novel nonribosomal peptides and facilitate the access to new biologically active peptide compounds.