Conventional syntheses in organic chemistry often use hazardous substances, consume large amounts of energy and generate toxic waste. An alternative is the use of biocatalytic ways performed in one pot by using simultaneously two or more enzymes in cascade avoiding the isolation of intermediates, thus saving time, energy, and limiting waste. The enzymatic approach is particularly useful for obtaining a-hydroxyketones moieties found in highly diverse classes of natural products that are of great importance due to their bioactivity, and their function as chiral building blocks for the synthesis of pharmaceuticals and agrochemicals. The chemical synthesis of stereoisomerically pure a-hydroxyketones is difficult and typically requires uneconomical steps for protective group manipulations. Carboligases such as thiamine dependent enzymes are particularly suitable and efficient to obtain a-hydroxyketones. Among them, the thermostable Transketolase (TK) from Geobacillus stearothermophilus, shows great advantages for obtaining a wide range of a-hydroxyketones according an irreversible reaction from an a-ketoacid and an aldehyde rendering the reaction irreversible by the release of carbon dioxide. The presentation will focus on the development of different strategies involving TK only (wild type or variants) or coupled with other enzymes (aldolase, transaminase or aminoacid oxidase) in reaction cascades (sequential or simultaneous) for the in situ generation of the TK substrates.
HECQUET Laurence, Institute of Chemistry of Clermont-Ferrand (ICCF)– UMR6296 CNRS- University Clermont Auvergne (UCA)
EDUCATION
2000 Habilitation to supervise research (HDR)
1992 PhD in Bioorganic Chemistry
1989 Master in biochemistry and molecular biology
PROFESSIONAL EXPERIENCES
1989-92 Industrial PhD thesis at Sanofi company, Grasse, France
1992 Assistant professor in organic chemistry at University
Clermont Auvergne, France
1997-99 CNRS fellowship: Karolinska Institute
(Pr. Günter Schneider), Stockholm, Sweden
2000- Full Professor in organic chemistry at University Clermont
Auvergne, France
2017-26 Deputy director of Institute of Chemistry of Clermont-Ferrand, France
PROFILE
Topics of research: carboligation reaction, enzyme engineering, immobilization, development of high throughput screening assays, enzymatic synthesis of chiral compounds, cascade reaction. Awards: distinguished member of French Chemical Society (SCF, 2015)
Project and network management:
- European Networks: Vice-Chair of COST action CM0701 “Cascat” (2008-2012), member of the management committee of COST action CM1303 “SysBiocat” (2013-2017), member of the steering committee of International Symposium (Biotrans), Chair of International Symposium Biotrans (25-29 June 2023, La Rochelle, France)
- European programs: supervisor Bilateral ANR program France/Germany deoTK (2009- 2013), supervisor bilateral ANR program France/Germany ThermoTK (2014- 2017), EraCoBiotech-Tralaminol PI WP1 (2018-2022), ITN CC-TOP PI WP3 (2022-2025)
- National Networks: Chair of Club Biocatalysis in Organic Synthesis (CBSO), French network of 17 laboratories private/academic (2006-present), Chair of Chemistry and Biotechnology group of French Chemical Society (SCF)
- Regional programs: Biocat (2004-2007), SynBIO (2009-2012), Bio3 (2012-2015), Pack Ambition Research (2018-2021)
- Industrial contracts: Fournier Pharma (Dijon-France), Greentech (Saint Beauzire-France), Glycotrade (Hamburg-Allemagne)
