Researchers at the University of Kent have discovered a new way in which nature makes heme – the component that gives blood its colour and allows red blood cells to carry oxygen around the body.
Until now it was not known that heme, one of the key pigments of life, can be made from a related molecule called siroheme by some very unusual and unexpected chemical processes – a discovery that principal investigator Professor Martin Warren has described as being similar in importance and scale to the transformation of the first electronic calculators into the modern mobile phone.
Heme performs many roles in the biology of a very large number of organisms. It is perhaps more well-known for the role it performs when it is found attached to the large protein globin – together called haemoglobin. Molecules attached to proteins in such a way that allows them to perform a role are known as prosthetic groups. Both the protein and the prosthetic group have to be synthesised from basic building blocks and then stuck together – all via various chemical processes in human cells.
In a Biotechnology and Biological Sciences Research Council (BBSRC) funded collaboration with the University of Oxford and Portugals Instituto de Tecnologia Química e Biológica (ITQB), the team from Kents School of Biosciences studied the process by which heme is synthesised in Archaea (a unique type of single-celled organism). Using state-of-the-art anaerobic facilities on Kents Canterbury campus, they showed at a molecular level that, within Archea, siroheme is hijacked and brought into the chemical process that synthesises heme. In molecular and cellular biochemistry this is a very rare example where one prosthetic group is cannibalised for the synthesis of another.
The project involved studying a number of very unusual biochemical reactions in glove-boxes that are completely devoid of oxygen. It was only under these unique conditions that the researchers were able to observe the reactions taking place.
Professor Warren, who is Head of the School of Biosciences at Kent, said: This is a very important piece of basic science that offers an explanation as to how biochemical pathways evolve and become more complex. Moreover, we have learnt some new concepts about how chemistry can be used to change the shape and the character of larger molecules, which can then be applied for the development of new compounds; for instance, in the pharmaceutical industry or the production of biofuels. In this respect our research contributes to the field of synthetic biology.
Professor Warren also explained that the new nuclear magnetic resonance (NMR) spectroscopy machine within his School was invaluable during the process. The extra sensitivity of this machine allowed the structure of new intermediates on the pathway to be determined, he said.
Molecular hijacking of siroheme for the synthesis of heme and d1 heme (Shilpa Bali, Andrew D. Lawrence, Susana A. Lobo, Lígia M. Saraiva, Bernard T. Golding, David J. Palmer, Mark J. Howard, Stuart J. Ferguson and Martin J. Warren) was published by Proceedings of the National Academy of Sciences of the United States of America (PNAS), the official journal of the United States National Academy of Sciences, on 3 October.