Despite years of effort, including sequencing the gut microbes of thousands of volunteers, the functions of the vast majority of the proteins found in this microbial community - as many as 85 percent - still remain a mystery. Many of these proteins are likely enzymes, the biological catalysts that allow living organisms to perform chemical reactions. Uncharacterized enyzmes in the human gut microbiome could be carrying out chemical processes that are critical for our health, but are currently unrecognized.
Hope may be on the way.
A new tool, developed by researchers more accurately identify enzymes present in microbiomes and quantify their relative abundances. The study is described in a paper published in Science.
"This is an interesting thing to be able to do, because with our method...in addition to identifying known microbial enzymes, we can get information about the distribution and abundance of enzymes with unknown activities," senior author said. "A major challenge associated with microbiomes has been how to interrogate the uncharacterized genetic potential of these communities - how do you go from genes in the human microbiome to new microbial metabolic activities...and we believe this could be a tool to do that."
It's already proven useful - armed with the new technique, researchers were able to, for the first time, appreciate just how common an uncharacterized glycyl radical enzyme was in the healthy human gut microbiome. They were also able to elucidate what this new enzyme actually does.
"This uncharacterized enzyme was the second most abundant glycyl radical enzyme in every person sequenced as part of the Human Microbiome Project, and its universal distribution strongly suggested it was doing something important" author said. "It turns out to have a fascinating function. It's allowing microbes to metabolize an amino acid called 4-hydroxyproline, which is a major component of collagen, the most abundant protein in the human body. We've discovered how microbes use this amino acid to grow in the anaerobic environment of the human gut."
"We were interested in the challenge of distinguishing members of the same enzyme family that have different activities from one another," author said. "Members of a human family can be closely related but have very different occupations, and this is also the case for enzyme families. A family of enzymes can be similar in terms of their amino acid sequences, but the individual members of the family have often evolved to perform very different chemical transformations."
"In the future we can start to think about things like comparative analyses," senior author said. "In this paper we only looked at data from healthy humans, but we'd really like to compare the abundance of enzymes in microbiomes from healthy individuals and patients suffering from various diseases. This could give us a glimpse into how metabolic activities in the gut microbiome might be changing with disease. If there are certain enzymes that are particularly abundant in patients with a given disease, they could be potential therapeutic targets."