Soumillion P.

DIRECTED EVOLUTION OF ENZYMES

GROUP LEADER

PATRICE SOUMILLION	Profile
	Prof. Patrice Soumillion is one of the group leaders of the research on enzyme engineering and accelerated evolution in the group of "biochemistry and molecular genetics of bacteria (BGMB)". Master's Degree in chemistry and Ph.D. in biochemistry at UCL (1994). Postdoctoral training at PennState University (USA, Prof. S.J. Benkovic), Research associate at FNRS (1998-2006), and Associate Professor at UCL since 2006. Fields of expertise:  Enzymology and protein biochemistry (beta-lactamases, DD-peptidases, penicillin acylase, inteins) Phage display and directed evolution technologies
Biochemistry and Molecular  Genetics of Bacteria (BGMB)    Bt. Carnoy (c.457) 4-5 Place Croix du Sud (bioc) B-1348 Louvain-la-Neuve-Belgium	Email : Tel. +32 10 47 30 75 Fax. +32 10 47 28 25

RESEARCH OVERVIEW

Research activities are focused on the directed evolution of enzymes using the phage display technology. Our group is currently developing innovative in vitro selection strategies for evolving enzymatic functions such as catalysis, substrate specificity and activity regulation.

The main scientific objectives are:

• Evolution between phylogenetically related activities
• Creation of artificial allosteric regulation sites
• Engineering protein reactivity 

The phage display technology for selection of catalysts

In order to understand how new activities are appearing during evolution, we are searching for an artificial route of evolution between a DD-peptidase and a beta-lactamase activity. These two phylogenetically related enzymes form covalent adducts with penicillins. This acyl-enzyme is stable in the case of DD-peptidases but rapidly hydrolysed in the case of beta-lactamases. We are developing innovative phage display methods for selecting mutants featuring improved deacylation rate from libraries of DD-peptidases.

Engineering enzyme regulation is of great interest for developing new biosensors and for understanding the structure-function relationships underlying an important natural characteristic of many enzymes. By introducing degenerated peptides in surface loops of the phage displayed TEM-1 beta-lactamase, we are creating large libraries of insertants from which we are selecting clones that have acquired affinity for specific ligands (proteins, ions, small molecules). The activity of most of these hybrid enzymes are up- or down-regulated upon ligand binding.

Enzymes are capable of bond-breaking and/or bond-making. Beside their catalytic properties, an important feature of enzymes is chemical reactivity. Since engineering catalysts remains very challenging, we are also applying directed evolution strategies,  for searching new reactive proteins. Current projects are focused on engineering protein splicing, auto-phosphorylation or nucleophile activation.

More on research projects >

STAFF 2012

DIRECTED EVOLUTION OF ENZYMES TEAM 2012 (BGMB)