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Biography

Jean M François got his PhD in Biological Science and Agronomy from the University of Louvain (Belgium) in 1988. He is Professor of Industrial Microbiology and
BioNanotechnology at the Federal University of Toulouse, School of Engineer. His research activity concerns integrated physiology and functional genomics in
microbial systems, with a specifi c focus on carbon and energy metabolism in yeast and fi lamentous fungi . He is author of more than 180 papers and 15 patents
and Editor in Chief of BMC Biotechnology for Biofuels.

Abstract

The development of carbon effi cient pathways for added value (bio)chemicals production is the essence of White Biotechnology.
Th e limit of carbon conservation in all (bio)chemical syntheses is determined by the electron balance in substrate(s) and
product(s). Frequently, natural metabolic networks do not have the stoichiometric capacity to produce a value-added compound
at yields that correspond to the thermodynamic maximum. A good example of natural metabolic networks lacking stoichiometric
effi ciency is the bioproduction of glycolic acid (GA), a two carbon compound of considerable industrial interest notably in cosmetics
and biodegradable polymers. We addressed this objective to approach this maximal conversion yield by employing the following
strategies. Firstly, we reconsider a completely diff erent route of C5 assimilation that by-passes the decarboxylation reaction in the
pentose phosphate pathway and that rely on the carbon-conserving aldolytic cleavage of X1P or R1P to yield the C2 compound
glycolaldehyde and the C3 DHAP compound. Th is metabolic scheme required the expression of human hexo(fructo)kinase(Khk-C)
and human aldolase (Aldo-B). Th en glycoaldehyde can be either reduced by endogenous aldehyde reductase to produce ethylene
(EG) glycol or oxidized into glycolic acid. With this approach, we obtained yield of EG and GA close to maximal theoretical yield of 1
mol/ mol sugar. Interestingly, we found that the engineered strain expressing this synthetic pathway exhibited a remarkable rewiring
of the metabolic networks that culminate with a dramatic reduced metabolites and metabolic energy levels. We then combined this
synthetic pathway with the natural glyoxylate shunt that can be engineered to produce GA from DHAP. Th is combination led to
an optimized production strain that produced ~30 % more GA from a xylose/glucose mixture (66%/33%) than when the natural
pathway is working alone.