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Enzyme Displays Astonishing Property

Marielle Lemaire and her team at SEESIB,1 who study enzymes that form sugar analogues, have made an accidental and unexpected discovery: an enzyme that can produce both glucose and fructose depending on the substrate it uses.
Her team and that of Pere Clapès2 in Spain are looking for therapeutic solutions to treat diseases affecting the lysosome, an organelle of the cells whose function is intra-cellular digestion, carried out by over 50 enzymes. In these rare genetic afflictions, a deficient gene leads to the production of ill-built enzymes, which cannot play their natural role of biocatalyst. Their deficiency generates a toxic accumulation of metabolites (the natural substrates or molecules upon which an enzyme acts) within the cells.
For a few years now, a therapeutic strategy called “chaperon molecular therapy” aims to create small chaperon molecules, which, combined with the ill-built enzyme, will restore its functional form and reinstate its biocatalytic properties. The researchers' goal is to produce chaperon molecules that look like the natural substrate of the targeted enzyme so that chaperon and enzyme will easily interact with one another.
In this field, Lemaire was particularly interested in some glycosidases, enzymes that digest sugars in the lysosome. Her team wanted to create specifically-designed chaperons that resembled sugars and would be tested as chaperons for glycosidases. To do so, one can use enzymes that catalyse the formation of sugar analogues. A few months ago, her team began studying one of these “resource” enzymes: D-Fructose-6-phosphate Aldolase, which usually produces sugars from the fructose family. What they stumbled on was an unusual peculiarity: this specific aldolase also creates sugars of the glucose family, an ability never described before within the scope of this enzyme group. “What makes this enzyme exceptional is its ability to catalyse reactions with varied substrates. Usually, enzymes, like locks, only work with one key and only generate a reaction with specific molecules,” explains Lemaire.
This “exotic” property, “absolutely stunning for scientists working in our field,” has been described in an article labelled VIP—Very Important Paper.3 The perspectives opened by this discovery remain to be explored: from diabetes treatment to artificial sweeteners, it will all depend on where industry takes it.

Marie-Hélène Towhill

Notes :

1. Laboratoire Synthèse et études de systèmes à intérêt biologiques, Aubière (CNRS / Université Blaise Pascal).
2. Instituto de Quimica Avanzada de Cataluña-CSIC, Barcelona.
3. X. Garrabou et al., “Asymmetric Self- and Cross-Aldol Reactions of Glycolaldehyde Catalyzed by D-Fructose-6-phosphate Aldolase,” Angew Chem Int Ed Engl., 2009. 48: 5521-5.

Contacts :

Marielle Lemaire,
SEESIB, Clermont-Ferrand.


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