Variants of glycosyl hydrolase family 2 beta-glucuronidases

Conference Dates

September 15-19, 2019


Mammals remove toxic metabolites and xenobiotics by attaching glucuronic acid to compounds targeted for excretion. The glucuronide increases the solubility of the compound, enabling secretion in urine or bile. Metabolites of opiates and opioids can be quantified from urine by hydrolyzing conjugates with β-glucuronidase (β-GUS) and separating free drug molecules by liquid chromatography and mass spectrometry (LC-MS). Importantly, the hydrolysis step increases both detection and quantitation because free drug molecules ionize better than conjugates in MS (Sitasuwan et al., 2019). However, not all glucuronidases have the same activity across a range of potential substrates. Therefore, we generated β-GUS variants with improved activity on a broader range of drug metabolites by using efficient domain swapping and site-saturation mutagenesis techniques.

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