Find out more about our ambitious upgrade project, delivering more brightness, more coherence, and greater speed of analysis to UK science. More about Diamond-II
Find out more about Diamond's response to virus research.
Scientists have identified the mechanism through which our gut bacteria digest a complex chain of sugars, or glycan, known as Rhamnogalacturonan-II (RG-II), found abundantly in apple juice and red wine.
The team, based at Newcastle University, write in the journal Nature that they have identified a species of the human gut microbiota, known as HGM, capable of using RG-II as a nutrient. The HGM is responsible for synthesising vital nutrients, and provide around 10% of our calorific intake by metabolising glycans into short-chain fatty acids, which are important for gut health in addition to providing energy to our bodies. In short, our bacterial flora covers every part of the human body. These bacteria, which outnumber our own cells by ten-to-one, play a huge role in human health.
“Understanding how bacteria in the gut work, and how they metabolise different nutrients, is vital in our understanding of how we might best work with our gut bacteria to encourage the growth of microbial populations which are beneficial to health, whilst identifying which species could be harmful,” says Professor Harry Gilbert, the leader of the project, based at Newcastle University’s Institute for Cell and Molecular Biosciences. “We know that they play a huge role in human wellbeing, but not enough is yet known about the complexities of their metabolism.”
RG-II has been a feature of the human diet for hundreds of thousands of years, and so is likely to have driven the evolution of HGM bacteria. A robust glycan, it does not degrade through processing associated with the preparation of food or drink, hence its accumulation in wine, where other sugars are broken down during the fermentation process. Together the RG-II team used over 150 litres of red wine to extract the polysaccharide – a long chain of sugar molecules – through a process of concentration by separating substances based on their electrical charge.
“Fortunately we were able to use cheap wine, as RG-II is just as abundant,” explained Professor Gilbert. “Mapping these structures will help us identify similar enzymes in soil environments, which will explain why RG-II does not accumulate in the soil despite being in every plant cell.”
RG-II was, for many years, thought too complex to be digested by single microbial species, and as such no-one had ever attempted to break down the glycan. By successfully doing so the team revealed a complex picture adding to our understanding of the molecule itself, and revealing seven previously undiscovered enzyme families, as well as uncovering new enzymatic activities.
Professor Harry Gilbert has been working on the project since 2010, after evidence that the molecule was being metabolised in the gut was found.
“After a couple of disappointing years of research when we made little progress, we decided to give a final push at the project for six months before moving on,” Professor Gilbert continues. “Solving this problem has been our Holy Grail since 2010, and this paper is the culmination of years of dedication and hard work.”
“Revealing seven new families of enzymes involved in this process is a huge achievement,” adds Professor Gilbert. “The hard work of my two postdocs, Didier Ndeh, and Artur Rogowski, was particularly crucial to this complex process - without their dedication we would have not been able to achieve this breakthrough.”
These structures reveal the unexpected configurations of the sugar in the active site of several enzymes, and will be vital in understanding glycan metabolism.
The team utilised three macromolecular crystallography (MX) beamlines, I02, I04-1 and I24, at Diamond Light Source, the UK’s national synchrotron facility. The crystal structures of six of the seven new enzyme families have now been determined, showing how these biocatalysts bind to their substrates revealing the mechanism of catalysis.
Diamond Light Source is the UK's national synchrotron science facility, located at the Harwell Science and Innovation Campus in Oxfordshire.
Copyright © 2022 Diamond Light Source
Diamond Light Source Ltd
Diamond House
Harwell Science & Innovation Campus
Didcot
Oxfordshire
OX11 0DE
Diamond Light Source® and the Diamond logo are registered trademarks of Diamond Light Source Ltd
Registered in England and Wales at Diamond House, Harwell Science and Innovation Campus, Didcot, Oxfordshire, OX11 0DE, United Kingdom. Company number: 4375679. VAT number: 287 461 957. Economic Operators Registration and Identification (EORI) number: GB287461957003.