Investigation on the Detoxification of Indoxyl Sulfate (IS) and Indole-3-Acetic Acid (IAA) Protein-Bound Uremic Toxins (PBUTs) Using Trametes versicolor Biocompatible Laccase: In Situ Synchrotron Imaging, Experimental and Computational Studies

Sana Daneshamouz ¹, Shaghayegh Saadati ², Sishi Zhu ¹

⁰Department of Chemical and Biological Engineering, University of Saskatchewan, 57 Campus Drive, Saskatoon, SK, S7 N 5 A9, Canada.

Applied Biochemistry and Biotechnology +

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May 19, 2025

View abstract on PubMed

Summary

Laccase enzyme decomposed indole-3-acetic acid (IAA) into less toxic byproducts, but did not affect indoxyl sulfate (IS) removal in hemodialysis (HD). Further research is needed for effective protein-bound uremic toxins (PBUTs) removal.

Area Of Science

Biochemistry
Biotechnology
Nephrology

Background

Protein-bound uremic toxins (PBUTs), including indoxyl sulfate (IS) and indole-3-acetic acid (IAA), are difficult to remove in hemodialysis (HD) due to strong albumin binding.
Effective removal of PBUTs is crucial for improving outcomes in HD patients.

Purpose Of The Study

To investigate the potential of laccase enzyme from Trametes versicolor for decomposing and removing IS and IAA during HD.
To assess the toxicity of laccase-generated byproducts and their impact on toxin-protein binding.

Main Methods

Molecular docking to study laccase-toxin interactions.
Liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) for toxin and byproduct analysis.
Synchrotron radiation micro-computed tomography (SR-µCT) to analyze toxin-albumin binding on HD membranes.

Main Results

Laccase effectively decomposed IAA into five less toxic byproducts, but IS remained unaffected.
Laccase treatment reduced albumin-IAA adsorption on HD membranes, but not albumin-IS adsorption.
The liver's conversion of indole to IS suggests laccase may not be ideal for IAA detoxification in HD.

Conclusions

Laccase shows limited efficacy for simultaneous removal of IS and IAA in HD.
Enzyme-based strategies require careful consideration of toxin metabolism and enzyme specificity.
Further research is needed to develop novel methods for PBUTs removal in hemodialysis.

Keywords:

Detoxification GC–MS Indole-3-acetic acid Indoxyl sulfate Laccase Molecular docking