Exploring modular reengineering strategies to redesign the teicoplanin non-ribosomal peptide synthetase |
| |
| Authors: | Milda Kaniusaite Robert J. A. Goode Julien Tailhades Ralf B. Schittenhelm Max J. Cryle |
| |
| Affiliation: | The Monash Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Monash University, Clayton Victoria 3800 Australia.; EMBL Australia, Monash University, Clayton Victoria 3800 Australia ; The Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, Monash University, Clayton Victoria 3800 Australia ; Monash Proteomics and Metabolomics Facility, Monash University, Clayton Victoria 3800 Australia |
| |
| Abstract: | Non-ribosomal peptide synthesis is an important biosynthesis pathway in secondary metabolism. In this study we have investigated modularisation and redesign strategies for the glycopeptide antibiotic teicoplanin. Using the relocation or exchange of domains within the NRPS modules, we have identified how to initiate peptide biosynthesis and explored the requirements for the functional reengineering of both the condensation/adenylation domain and epimerisation/condensation domain interfaces. We have also demonstrated strategies that ensure communication between isolated NRPS modules, leading to new peptide assembly pathways. This provides important insights into NRPS reengineering of glycopeptide antibiotic biosynthesis and has broad implications for the redesign of other NRPS systems.Redesign of the non-ribosomal peptide synthetase (NRPS) from teicoplanin biosynthesis has been extensively investigated via domain exchange, interface reengineering and through engineering communication between isolated NRPS modules. |
| |
| Keywords: | |
|
|
