Cofactors are to enzymes what tools are to workers. Benoît Desguin has discovered a new ‘tool’, a cofactor containing nickel, and intends to identify the family of enzymes that use it to accomplish their tasks.
Covering a lot of ground on bike or in the lab doesn’t scare Dr Desguin. He often rides his recumbent bike the 25 kilometres from Nivelles to his laboratory at the Louvain Institute of Biomolecular Science and Technology (LIBST) in Louvain-la-Neuve, where he has also come a long way since his 2008 master’s dissertation. ‘I chose bioengineering studies because I’m very interested in the mechanisms that govern nature and the world in general’, he says. ‘These studies are in my view a good compromise between a fundamental and applied approach. In my dissertation, I worked on the genetic modification of a bacterium used by a company to improve the productivity of lactic acid.’ Lactic acid bacteria have been used by humans for thousands of years to ferment certain foods such as dairy products, but they’re also sometimes found in products such as cosmetics and biodegradable plastics.
Sparks fly from an ‘old’ thesis topic
Excited by his dissertation research, Dr Desguin envisioned pursuing it further. His supervisor, Pascal Hols, suggested a PhD thesis topic. ‘It was an old, difficult thesis subject that had been unfinished for several years’, he explains. And yet the ‘new’ researcher ignited the ‘old’ subject. ‘During my thesis research I discovered the enzyme lactate racemase, which converts lactic acid from its D form to its L form and vice versa, two mirror forms of the molecule.’ It was a valuable discovery given that the preferred form depends on what the acid will be used for. ‘The enzyme needs nickel to function, as well as several proteins, a regulator and a carrier.’ He had made encouraging progress…and yet: ‘My feeling after my thesis was that a central element was still missing in our understanding of the system.’ He soldiered on. In 2013, he joined the Department of Biochemistry and Molecular Biology at Michigan State University (USA) for a two-year postdoctoral fellowship.
The missing link: a cofactor
At MSU, Dr Desguin says, ‘Professor Robert Hausinger allowed me to continue my research in his laboratory. It's rare to have this kind of opportunity.’ The professor's confidence in the young researcher and his research topic quickly paid off. ‘That's where I discovered that the lactate racemase enzyme works through a cofactor that contains nickel. Enzymes can be compared to workers who each need specific tools. The cofactor is the enzyme’s tool. In the case of lactate racemase, the tool consists of a new type of cofactor which has a kind of clamp in which the nickel is housed.’ These results were published in Science in 2015. When Dr Desguin returned to UCL, he received an FNRS postdoctoral researcher grant to continue studying the cofactor under the supervision of Patrice Soumillion and Pascal Hols. ‘I analysed how it’s made and I managed to reproduce it in the lab.’ Now selected for a position as an FNRS research associate, Dr Desguin has the opportunity to plan his long-term research. ‘I’d like to identify all the other enzymes that use this cofactor and thus bring to light a new family of enzymes that we never thought existed.’