Hydrogen and carbon dioxide biochemistry in the bacterial energy-transducing membrane.

Developing renewable energy sources and reducing carbon dioxide emissions will require a basket of different solutions. Biology offers some good options. Microbiology offers some really exciting ones. Microscopic, single-celled bacteria are used to living in extreme environments and often perform (bio)chemical reactions that plants and animals cannot do. Many bacteria retain the ability to grow in the complete absence of oxygen. Under such conditions a special enzyme called formate hydrogenlyase is produced in the cell. This enzyme oxidises formate to carbon dioxide and two electrons, and those two electrons are channeled down a molecular wire in the protein and used directly to generate hydrogen gas (H2). Formate hydrogenlyase are attached to the cell surface when they do H2 production and, somehow, they use this activity to transport other hydrogen ions (protons) across the membrane, which can be used to make ATP for cellular energy. On the face of it, formate hydrogenlyases must use the same mechanism to do this that is also found in the human mitochondrion (making ATP for the human cell). It should be easier and quicker to study this mechanism in bacteria and therefore make new discoveries about the fundamental rules of life.

What about societal impact and benefit? Most enzymes in the world are reversible. The reverse reaction of formate hydrogenase would be to take H2 and carbon dioxide and generate formic acid. Thus, running formate hydrogenlyase in reverse should allow a bacterium to use hydrogen as a substrate to capture carbon dioxide as soluble formic acid. Using renewable H2 would be even better, as this would make this form of biological carbon capture really sustainable and useful to society. Harnessing this enzyme activity - either within cells as a "whole cell biocatalyst" or outside cells as an isolated protein - has the potential to help reduce carbon dioxide emissions from a whole range of sources, and to convert that CO2 waste into more useful products.

'Biohydrogen' is the production of molecular hydrogen (H2) by living organisms. Formate hydrogenlyases are bacterial enzymes that can either produce molecular hydrogen gas or use H2 to convert carbon dioxide to formic acid, thus potentially contributing doubly to a sustainable energy future. The structure of formate hydrogenlyase reveals a membrane-bound redox enzyme that shares a common ancestor with the mitochondrial complex I (NADH dehydrogenase). As so-called 'complex-I-like' enzymes, formate hydrogenlyases comprise a membrane arm (possibly driving proton transfer) and a peripheral arm (driving electron transfer). Generating new knowledge on how the two arms of formate hydrogenlyases work together will unlock secrets of fundamental cellular bioenergetics, and could even shine new light on the molecular basis of human mitochondrial function and dysfunction. In this project, we aim to answer the key questions on the structure and function of these enzymes; to explore the interrelationship between the membrane arm and the energy-transducing membrane; and to apply this unique enzymatic activity to tackle global challenges.