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Thesis: Structure and Dynamics of Non Ribosomal Peptide Synthetases

Hooghwinkel, M.E. (2017) Thesis: Structure and Dynamics of Non Ribosomal Peptide Synthetases. Bachelor's Thesis, Biology.

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Secondary metabolites make up a large class of socially relevant compounds. Many of these, like antibiotic Vancomycin and anticancer agent Bleomycin, are produced by Non-Ribosomal Peptide Synthetases (NRPSs). Named Non-Ribosomal Peptides (NRPs), these compounds often contain non-proteinogenic amino acids and often have other interesting features, like e.g. a cyclic architecture. NRPSs are large, modular enzyme complexes, arranged in a beads-on-a-string-like manner, and work much like an assembly belt as each module activates a single substrate and adds it to the growing peptide product chain. Engineering these complexes to add non-native substrates to their product peptides opens up exciting possibilities, as this may be an easy way to produce new, custom peptides. Engineering NRPSs is difficult, however, due to their great size and the many interactions that take place in-protein; attempts to change substrate specificity often result in a drastically lowered turnover. Detailed structural data may help to solve issues contributed to the breaking of protein-protein interactions. Unfortunately, no complete structure of any NRPS is currently available. This is attributed again to the size of the proteins, but also the flexibility and the many conformational changes the enzyme undergoes in its catalytic cycle. Structures of dissected catalytic domains, didomains and modules are abundant, however, and may be combined to get a model of the full structure of a NRPS. Recently, this was done by Marahiel (2015), providing exciting new insights into the structure and dynamics of NRPSs, and bringing the possibility of functional engineered NRPSs closer than ever.

Item Type: Thesis (Bachelor's Thesis)
Degree programme: Biology
Thesis type: Bachelor's Thesis
Language: English
Date Deposited: 15 Feb 2018 08:28
Last Modified: 15 Feb 2018 08:28

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