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Home > Departments > Microbiology > Sylvie LAUTRU : Molecular Microbiology of Actinomycetes

Biosynthesis of specialised metabolites

We are particularly interested in the global specialized metabolism of a strain, Streptomyces ambofaciens. We are also interested in the biosynthesis of some specific families of specialized metabolites, the pyrrolamides and the diketopiperazines

In the past decades, our knowledge of specialized bacterial metabolism has improved considerably. The advances are in particular due to the development of OMICS methods (genomics, transcriptomics, metabolomics, etc.)
The sequencing of numerous Streptomyces genomes has shown that these bacteria have several dozen groups of genes directing the biosynthesis of specialized metabolites. These genes are preferably located in the extremitiesof the linear chromosome, regions that are very variable between Streptomyces species and that can evolve rapidly.

 

Repertoire of Streptomyces ambofaciens specialised metabolism

Streptomyces ambofaciens ATCC23877 was isolated from the soil of Péronne (France). It has been known for around sixty years for producing spiramycins (I, II and III), used as antibiotics in human medicine, and congocidine (netropsin), isolated in the 1950s. Sequencing and analysis of its genome has shown that S. ambofaciens possess 25 specialized metabolism gene clusters, many of which are now known. We are now seeking to explore the secondary metabolism of S. ambofaciens as comprehensively as possible using a variety of approaches, including in particular OMICS and genome mining approaches.

 

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Schematic representation of the chromosome of S. ambofaciens and of the identified specialized metabolism gene clusters. The names of some metabolites biosynthesized by the strain are given. TIR: Terminal Inverted Repeats.

 

Biosynthesis of pyrrolamides

Pyrrolamides (e.g. congocidine, distamycin, kikumycins, pyrronamycins, noformycin), constitute a family of natural products produced by Streptomyces or related actinobacteria that exhibit a variety of biological activities (antiviral, antibacterial, antitumor or anthelmintic activities for example).
Isolated about sixty years ago, the two best characterised members of the pyrrolamide family, congocidine (also called netropsin) and distamycin, have been extensively studied due to their ability to bind to the minor groove of the DNA double helix in a sequence-specific manner.

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Congocidine bound into DNA minor groove

 

We have characterized several groups of pyrrolamide biosynthesis genes, starting with that directing the biosynthesis of congocidine in Streptomyces ambofaciens. We have since characterized the biosynthetic gene groups of distamycin and anthelvencin.

 

 

by ACTINO - published on , updated on