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Home > Departments > Microbiology > Jean-Luc PERNODET : Molecular Microbiology of Actinomycetes

Synthetic Biology of specialised metabolites

We are developing tools and approaches for synthetic biology, approaches centered around diketopiperazines and pyrrolamides.

Synthetic biology can be defined as the engineering of an organism to give it functions that it does not naturally possess. In the field of specialized metabolites, there are several objectives for synthetic biology: the refactoring of cryptic biosynthetic gene clusters (not expressed under laboratory culture conditions) to allow their expression and the production of metabolites; the development of genetic tools allowing the control of genes expression (promoters and synthetic RBS) or strains optimized for the production of specialized metabolites; or the engineering of a biosynthetic pathway for the production of new metabolites.

Construction of tools for synthetic biology in Actinobacteria

We have constructed vectors designed to assemble DNA fragments in Escherichia coli and that can be integrated at various locations in the Streptomyces chromosome with site-specific integration systems (see "Tools" tab).

 

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Modular vectors constructed for the cloning of gene clusters and their expression in Streptomyces

 

We are also constructing vectors for Amycolatopsis species.

 

Combinatorial biosynthesis of pyrrolamides

Pyrrolamides are assembled by enzymes from the non-ribosomal peptide synthetase (NRPS) family. NRPSs constitute a large family of enzymes involved in specialised metabolism. Some NRPSs are involved in the biosynthesis of metabolites used in medicine, including as antibiotics. Synthesizing new molecules by molecular engineering (combinatorial biosynthesis) could therefore constitute a new source of antibiotics. Numerous studies have shown that it is possible to synthesize new compounds by genetically engineering NRPSs. The yields with which these products are obtained are however in general (much) lower than the production yields of natural metabolites, illustrating the limits of our current knowledge of these enzymes.

We use the NRPSs involved in the biosynthesis of pyrrolamides as models to try to understand the factors limiting the combinatorial biosynthesis approaches based on NRPSs, using a synthetic biology approach.

 

 

by ACTINO - published on , updated on