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Tracking enzymes in the human intestinal tract

A researcher at the Institut Micalis (1) of the INRA Jouy-en-Josas Research Centre, Olivier Berteau is fascinated by the bacteria found in the digestive tract. His is an emerging field of research that is already marked by fierce international competition. In 2013, he received a grant from the European Research Council for a project at the interface between chemistry and biology, aiming at studying a family of emerging enzymes which catalyze chemically difficult reactions which are essential for living organisms.

Olivier Berteau. © INRA
By Magali Sarazin, translated by Emily Divinagracia
Updated on 01/07/2019
Published on 10/12/2010

“Our goal is to succeed in modifying the enzymes to better understand them.”

Olivier Berteau tracks the enzymes synthesised by these bacteria to modify food compounds or colonise their host. He wants to understand the specific role of these enzymes, which have been little scrutinised to date. Some of them, such as sulfatases, could become unrivalled catalysts in green chemistry and sustainable development.

Shedding light on sulfatases, vital enzymes in the human digestive tract

From the day in 2005 when he joined INRA's Unit for Ecology and Physiology of the Digestive Tract – which became the huge Micalis unit, with 23 INRA research teams, a few months ago – Olivier Berteau was drawn to sulfatases, enzymes that are needed for the elimination of sulfated compounds. The bacteria secreting them could not be cultured, but the scientist and his small team developed innovative solutions to study how their enzymes worked. "The sequencing of the human intestinal metagenome (2), completed in 2010, supported some of our hypotheses on bacterial adaptation to the human intestinal tract. While our gut offers a welcome environment for the implantation of many bacteria, with regulated temperature and food supply, only a few bacterial groups actually live there. The hundreds of bacterial species in the microbiota (3) come essentially from two large bacterial groups, Firmicutes and Bacteroidetes. A large number of genes coding for sulfatases were found in the latter group." The researchers thus demonstrated that the bacteria synthesising sulfatases "were overrepresented in the human intestinal tract, compared with bacteria isolated from other environments such as the soil or even other parts of the human body, like the mouth. We thus suspected them of playing a vital role in adaptation to the intestinal tract."

Discovering their key role in human health

What do these sulfatases do, then, given that humans do not eat sulfated food? To learn more, Berteau took an original, multidisciplinary approach. "We used techniques from genetics, molecular biology, physico-chemistry and biochemistry to purify and characterise the functions of these enzymes. I acquired these methodologies while working on my doctorate at the University of Paris 13 as well as my post-doctoral fellowships at the Swedish University of Agricultural Sciences and the Atomic Energy Commission in Grenoble."

Generally described as being involved in sulfur supplementation (a vital element for bacteria, as are carbon and nitrogen), sulfatases produced by bacteria in fact play an important role in the colonisation of the intestinal tract, as Berteau recently showed in vivo in collaboration with the University of Washington. "The more we learn about sulfatases," he said, "the more complex their functions turn out to be." He discovered that sulfatases can modify not only sulfated micronutrients but also sulfated compounds found in some of the tissues of the intestinal tract. "The commensal bacteria living inside us, some of which synthesise sulfatases, are generally thought to be beneficial to humans because by occupying the space they prevent pathogenic bacteria from settling in, and because they also produce vitamins needed by humans. The situation is quite complex, though, and more work is needed to understand the role of these bacteria and their enzymes in human health and physiology."

Applications in green chemistry and human health

Olivier Berteau and his team. © Import
Olivier Berteau and his team. © Import
At 40, the researcher is also involved in the PolyModE (4) European project involving fifteen partners. The scientists are building a library of new enzymes that, like sulfatases, are capable of modifying polysaccharides. The project should be a source of innovation for the development of new biological catalysts. Their work is eagerly anticipated by the pharmaceutical industry, which constantly seeks new molecules but also wants alternatives to chemical processes for sustainable development. "We are also thinking of integrating our research in the framework of synthetic biology (5). By producing sulfatase variants, we succeeded for instance in catalysing different reactions in unexpected ways, a result that was discussed in a recent article with Cambridge University. Our goal is to succeed in modifying the enzymes to better understand them. Perhaps one day we can create new enzymes ourselves," Berteau explained.

Thanks to two programmes funded by the French National Research Agency, Berteau is also studying other enzymes in the microbiota: a family of metallo-enzymes via the AdoMet project as well as the enzymatic system producing colibactin, a toxin that may be behind some forms of human cancers, as part of the aptly-named Colibactin project.

(1) Food Microbiology for Human Health, a joint research unit (INRA and AgroParisTech) of the INRA Jouy-en-Josas centre (Nutrition, Chemical Food Safety and Consumer Behaviour and Microbiology and the Food Chain divisions).
(2) Metagenomics analyses the genomes of a population without specifying individual genomes.
(3) Bacterial ecosystems colonising different organs: lung, intestinal tract, skin.
(4) PolyModE (Polysaccharide Modifying Enzymes) involves INRA as well as five academic partners, two multinationals from the food (Danisco) and pharmaceutical (Sanofi-Aventis) industries, and seven SMEs.
(5) Construction of complex living systems: the first synthetic bacteria was created at the Craig Venter Institute in May 2010

ERC Consolidator Grants

The ERC Consolidator Grants can amount to €2.75 million and are awarded to scientists with between 7 and 12 years' experience after obtaining their PhD, with a very promising scientific career ahead of them. Based on the sole criterion of excellence, this funding programme is designed to support exploratory, innovative and ambitious research projects that will open the way to new scientific and technological advances.

For more information on the 2013 grant recipients

In brief

  • 40 years old
  • Degree (Diplôme d'étude approfondie) in biological and medical engineering
  • Doctorate in Chemistry, specialising in Biomaterials
  • Winner of INRA's Young Researcher Award in 2010
  • Recipient of a ERC Consolidator Grant in 2013
  • Loves reading and music

On Winning the INRA Young Researcher Award

“There are a thousand ways of being a researcher. The INRA Awards recognise one of them - one that dedicated itself to an emerging topic, gave ideas time to mature, identified points of contention and formulated new hypotheses, all in the context of fierce international competition.”