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Activity‐Based Protein Profiling of Bile Salt Hydrolysis in the Human Gut Microbiome with Beta‐Lactam or Acrylamide‐Based Probes
Author(s) -
Brandvold Kristoffer R.,
Miller Carson J.,
Volk Regan F.,
Killinger Bryan J.,
Whidbey Christopher,
Wright Aaron T.
Publication year - 2021
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.202000748
Subject(s) - biochemistry , metabolism , microbiome , taurine , gut microbiome , chemistry , enzyme , hydrolysis , bile acid , salt (chemistry) , biology , gut flora , amino acid , bioinformatics
Microbial bile salt hydrolases (BSHs) found in the intestine catalyze the deconjugation of taurine‐ and glycine‐linked bile salts produced in the liver. The resulting bile salts are biological detergents and are critical in aiding lipophilic nutrient digestion. Therefore, the activity of BSHs in the gut microbiome is directly linked to human metabolism and overall health. Bile salt metabolism has also been associated with disease phenotypes such as liver and colorectal cancer. In order to reshape the gut microbiome to optimize bile salt metabolism, tools to characterize and quantify these processes must exist to enable a much‐improved understanding of how metabolism goes awry in the face of disease, and how it can be improved through an altered lifestyle and environment. Furthermore, it is necessary to attribute metabolic activity to specific members and BSHs within the microbiome. To this end, we have developed activity‐based probes with two different reactive groups to target bile salt hydrolases. These probes bind similarly to the authentic bile salt substrates, and we demonstrate enzyme labeling of active bile salt hydrolases by using purified protein, cell lysates, and in human stool.