C-C Bond Formation Using Top Performing Enzymes – Training the Next Generation of Innovators for a Sustainable Bioeconomy (CC-TOP)

Université Clermont Auvergne (UCA), France

Institute of chemistry of Clermont-Ferrand (ICCF-UMR 6296 CNRS)

"C-C Bond Formation Using Top Performing Enzymes  

Training the Next Generation of Innovators for a Sustainable Bioeconomy"

(CC-TOP)

Gross Salary : 3120 euros / month +/- 358 euros of family allowance (if eligible)

Start : Oct 2021

Lenght : 36 months (26 months at UCA/ICCF in France and 3 secondments in Germany (10 months)

Context

Université Clermont Auvergne (UCA) is a multidisciplinary higher education institution located in Clermont-Ferrand, France. The Institute of Chemistry of Clermont-Ferrand (ICCF) is a joint research unit between UCA and the National Center of Scientific Research (CNRS). ICCF aims to centralize the research activities in chemistry of the site including around 300 people. ICCF is structured around six research teams and three technical platforms with high level equipments offering strong specificities recognized at national and international levels in various multidisciplinary domains: Chemistry/Health/Biology/Physics/Materials. ICCF combines academic research and technology transfer which is illustrated by two Joint Research Laboratories with AREVA and MICHELIN, strong links with the regional socio-economic tissue (AURA region, local Startup and SMEs, competitiveness clusters) and by contracts with major national and international patent groups. ICCF has thus become an essential interlocutor of the site of Clermont-Ferrand with a network of collaborations with more than 22 countries and through 40 agreements guaranteeing the attractiveness of our Institute.

Objectives of the ITN CC-TOP

The main goal of the CC-TOP ITN is to train the next generation of multi-disciplinary researchers in order to boost the development and exploitation of carboligation enzymes for Industrial Biotechnology, in particular for production of novel chiral fine chemicals and pharmaceuticals. Therefore, CC-TOP will train 15 top early-career researchers in a mosaic of disciplines and technologies around enzymatic carboligation and its translation into industrial application. The networks aim for efficient translation of breakthrough technology into industrial application is emphasized through the implementation of an industrial skills module and measures for active innovation management involving all ESRs.

PhD Project (WP2 - ESR9)

• Aims : Thiamin Diphosphate (ThDP) dependent transketolases and glyoxylate carboligases for synthesis of chiral polyols. Industrially applicable wild type and variants TDP dependent enzymes from thermophilic bacteria such as transketolases (TK) and unexplored glyoxylate carboligases (GLC) will be evaluated for the conversion of a wide range of substrates into chiral polyols. For the most promising enzyme variants an integration in enzymatic cascade reactions allowing in situ generation of substrates will be conducted.
• Methodology : Directed evolution will be used to expand the TK and GLC substrate scopes. Variant libraries will be screened using high-throughput assays. Best variants will be characterized (steady-state kinetics, thermostability, crystal structure determination) and used in biocatalytic process. -Expected Results: 1) New thermostable TK and glyoxylate carboxyligase from thermophilic bacteria; 2) High-quality enzyme mutant libraries and selection of improved enzyme mutants; 3) full characterisation of enzymes by biophysical, kinetic and chemical analyses; 4) protocols for chiral polyols synthesis.
• Supervisors : Prof. Laurence Hecquet and Dr. Franck Charmantray
• Planned secondments :

(1) : TU Darmstadt (Germany), Prof. W.-D. Fessner, M12-M14 (3 months) : for metagenomic approach ;

(2) : University of Göttingen (Germany) Prof. K. Tittmann, M18-M21 (4 months) : for crystal structures determination;

(3) : BASF (Germany), Dr. M. Breuer, M29-M31 (3 months) : for industrial applications of TKs products (chiral polyols).

Applicants

The applicant will be in charge of the production of enzymes (expression, extraction, purification), characterization of enzymes (kinetic studies), development of high-throughput assays, implementation of enzymatic reactions, characterization of the products. The applicant must have a background in organic chemistry, biochemistry and appreciated skills in molecular biology, cristallography.

IMPORTANT : PhD student must not have resided or worked for more than 12 months in France in the last 3 years before the start of their contract and will have a maximum of 4 years of experience after graduation allowing enrollment in thesis.

Submission of applications

Required documents: curriculum vitae, cover letter, two recommendation letters

Submit your application on the CC-TOP web site : https://cc-top-itn.eu/cc-top-project/