Bacterial beta-glucuronidase (GUS) (GUS)

Bacterial beta-glucuronidase (GUS) is an enzyme produced by various members of the human gut microbiota, including Escherichia coli and Bacteroides species (Pollet et al., 2017, CMLS). Its primary biological function is to catalyze the hydrolysis of beta-D-glucuronides into glucuronic acid and an aglycone, a process central to the enterohepatic circulation that allows bacteria to utilize glucuronide sugars as a carbon source. While physiologically normal, this enzyme plays a detrimental role in pharmacology by reactivating toxic drug metabolites in the intestines. For instance, the chemotherapeutic drug irinotecan is detoxified in the liver to SN-38G, but bacterial GUS cleaves this conjugate back into the toxic SN-38 in the colon, leading to severe dose-limiting diarrhea (Wallace et al., 2010, Science). Selective inhibition of bacterial GUS, without affecting human beta-glucuronidase, is a promising strategy to alleviate these side effects and improve the safety of medications like NSAIDs and chemotherapy (Roberts et al., 2013, ACS Chem Biol). Additionally, the enzyme is implicated in colorectal cancer development through the reactivation of dietary carcinogens (Dashnyam et al., 2018, Oncotarget).

Other names

Beta-D-glucuronoside glucuronosohydrolaseGUSBGBacterial β-glucuronidaseuidA

Selective inhibition of the bacterial enzyme's catalytic site to prevent the deconjugation of drug-glucuronides, thereby reducing the local concentration of toxic aglycones in the gut (Wallace et al., 2010, Science).