Unlocking the secrets to enzymes, the catalysts of life
Life would not be possible without enzymes. The chemical reactions that generate the substances our cells and bodies need are all carried out by enzymes. Affecting every function, from breathing to digestion, this class of proteins is capable of enormously accelerating the rates of chemical reactions that would otherwise be impossible to bring about. However, to date, scientists have not quite understood how enzymes coordinate their activities within the cell – something that modern science now has the tools to address. For the MetaQ project, the focus is on a molecule called coenzyme Q, and how to biosynthesise it. While mainly known as an ingredient in beauty products, coenzyme Q is actually found everywhere in nature and is essential for life. It is a key chemical mediator of respiration, it functions as an antioxidant and alterations in its levels are linked to many diseases. “Due to its complexity, essential role in life and biomedical significance, the production of coenzyme Q serves as an ideal system to study how cells coordinate enzymatic activity in time and space,” explains project lead Andrea Mattevi from the University of Pavia in Italy. Coenzyme Q provides an ideal model through which to address the questions driving MetaQ research: How do enzymes ensure that they exchange molecules efficiently with one another? How do they prevent the wasteful loss or degradation of reaction products before these are processed by the next enzyme in the pathway? How is a specific enzyme recruited to one metabolic pathway over another? The hope is that the biosynthesis of coenzyme Q will provide the answers.
Not a soup, but an assembly
Since its launch in October 2023, MetaQ has uncovered several previously unknown chemical steps in the biosynthesis of coenzyme Q in human cells. “This represents a fundamental breakthrough, enabling a more comprehensive understanding of this essential metabolic pathway,” comments Mattevi. The team also discovered that the enzymes involved in this process come together to form a loose assembly that functions like a chemical factory. “In this arrangement, the series of reactions is carried out sequentially, minimising the loss of intermediate compounds that could be toxic to the cell,” the researcher notes. According to Mattevi, this is one of the first examples demonstrating that cells are not simply a “soup of enzymes,” with each enzyme performing its chemical reaction in isolation. “Instead, there are higher levels of organisation in which enzymes interact and co-localise to coordinate their activities, enhance their efficiency, and reduce the production of wasteful, or worse, harmful by-products.” Next on the project’s agenda is to develop and apply experimental tools to understand how this enzymatic machinery functions – how the enzymes come together, how they interact and how they coordinate their functions through physical proximity. MetaQ (When enzymes join forces: unmasking a mitochondrial biosynthetic engine) then plans to expand its research into other metabolic processes where enzyme orchestration enables complex chemical and metabolic functions with important biomedical implications. If you are interested in having your project featured as a ‘Project of the Month’ in an upcoming issue, please send us an email to editorial@cordis.europa.eu and tell us why!