Mots-Clés

réseaux métaboliques retrosynthesis biologie synthétique

Description

Subject

Prediction of natural and synthetic metabolic pathways in microbial consortia.

Context

Metabolic engineering aims to control the metabolism of living organisms, and in particular to optimize their assimilation and production capacities. It is a promising field, particularly for the biosourced production of molecules of interest to replace the non-renewable and polluting syntheses of organic chemistry. The production of molecules of interest by microbial consortia is nowadays a research field in full expansion, especially since traditional industrial systems generally belong to this category, especially in the food industry.

Retrosynthesis is a method developed for more than 50 years in chemistry which consists in finding chemical reactions participating in the synthesis pathways of a molecule of interest from a set of available products. The search for the pathways is carried out starting from the desired molecule and the reactions are reversed, hence the term “retrosynthesis”. The same concept has been applied in metabolic engineering under the term “bio-retrosynthesis” to emphasize the specific constraints of biology. Indeed, reactions must be catalyzed by enzymes whose genes must be known, and the synthesis pathways must be functional in living organisms. However, bioretrosynthesis has never been adapted to meet the specificities of a synthesis carried out simultaneously by several organisms, in consortia.

There is today a need related to the prediction of synthesis pathways in microbial consortia, and the exploitation of retrosynthesis algorithms could be a source of innovation.
In this context, the successful candidate will be asked to answer the following questions:

• Identification of natural pathways: does bioretrosynthesis is able to complete the metabolic networks of microbial strains (and consortia) used in biotechnology in order to identify its missing steps (gap-filling)?
• Prediction of new (synthetic) pathways: for a given target molecule, what are the most efficient microbial strains to perform its synthesis? Can we find a microbial consortium that allows production at a lower cost and better yield than a single strain?

In addition, the candidate will maintain the team’s bioretrosynthesis software and will be responsible for the competitive and technological watch related to his/her thesis topic.

The results of the thesis will be used to strengthen the design workflow of microbial consortia developed at iMEAN and will be the subject of peer-reviewed scientific publications by the academic team.

Profile

Master’s degree or engineering degree with a specialization in bioinformatics or chemoinformatics. A strong interest in synthetic biology, green chemistry, and/or metabolic engineering. Good organizational skills and ability to manage priorities, rigor, autonomy, ability to work in a team and independently. Knowledge in microbial physiology, especially metabolic physiology would be a plus.

Writing skills in English are essential, as well as a good knowledge of the Python programming environment and its best practices. Knowing French is not mandatory but would be considered an advantage.

Work environment

The academic team (Université Paris-Saclay, Micalis/INRAE, jfaulon.com, France) and the start-up (iMEAN, France) where the candidate will be recruited already have a good experience in the development of bioretrosynthesis tools and the design of genome-scale models. The successful candidate will benefit from a software package and the support of several researchers and bioinformatics engineers, biochemists and molecular biologists specialized in metabolic engineering and synthetic biology.

The workplace will be shared between:

• on the one hand, the academic laboratory at the Micalis Institute, an INRAE unit of the University of Paris Saclay (Vilvert Center, 78352 Jouy-en-Josas, France), where the work to improve the bioretrosynthesis algorithm will be carried out.
• on the other hand, the start-up iMEAN located in the buildings of Toulouse White Biotechnology (campus of INSA Toulouse, 31000 Toulouse, France) for work on modeling microbial consortia and coupling with bioretrosynthesis.

We expect the candidate to physically come to both workplaces during the course of the PhD. The distribution of working time should be equivalent between the two entities and can be adapted to the needs of the thesis.

Contract

In accordance with French legislation, the thesis will last three years. We wish to start September 2022 subject to approval of our CIFRE project by the ANRT. We expect the latter to take about 6 months. Meanwhile, we may provide the candidate with an university internship.

Salary

25 800 € annual gross salary