Nonribosomal peptide synthetases: engineering, characterization and biotechnological potential

Nonribosomal peptide synthetases or NRPS, are extraordinarily large, modular and complex molecular machines responsible for the production of important bioactive compounds, such as antibiotics, anti-cancer drugs as well as pigments, among many others. Even though it has become increasingly simple to identify and partially classify this kind of enzyme, it still remains an incredibly delicate task to harness their full potential. Since the dawn of the discovery and application of early antibiotics, there has been a thriving interest in the development of tools for the understanding and especially the engineering of NRPS. In nowadays world, where we face a global antibiotic-resistance crisis, the discovery and development of novel antibiotics has never been more crucial to fight this battle. This work does not only present a series of new tools and strategies, to develop and engineer NRPS, but furthermore elucidated fundamental ways to tackle and bypass major bottlenecks in the greater scheme of novel antibiotics development. The combined knowledge and strategies laid out in this thesis, may not only allow for the adaptation of already established antibiotics towards new applications, but could also pave the road towards a new, more robust next generation of antibiotic compounds, able to fulfill the demands of modern medicine.

Dissertation: http://hdl.handle.net/11370/6ea54e57-d551-4c36-864b-b41ae31faede