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Bioinformatic Analysis of Oxalate-Degrading Enzymes in Probiotics: A Systematic Genome-Scale and Structural Survey
Shengda Du1, Ke Sun2, Bo Xiao3
1College of Life Sciences, Northwest A&F University, Yangling 712100, China.
Abstract:
This bioinformatic study provides a comprehensive theoretical assessment of oxalate-degrading enzymes in probiotics. Kidney stone disease is a common urological disorder with rising global incidence, largely driven by the precipitation of insoluble calcium oxalate salts. Current treatments-including thiazides, lithotripsy, or ultrasound fragmentation-often show variable outcomes and high recurrence rates. Here, we systematically assessed the oxalate-degrading potential of 38 probiotic species listed in the List of Cultures Available in Food (China National Health Commission) along with selected next-generation probiotics. Using BLASTp homology searches, we identified seven strains carrying both oxalyl-CoA decarboxylase (OXC) and formyl-CoA transferase (FRC) genes, one encoding oxalate decarboxylase (OXDC), and three harboring subunits of oxalate oxidoreductase (OOR). Additionally, seven species from international probiotic lists (EFSA QPS and AEProbio) were analyzed, among which two carry both OXC and FRC genes. We prioritized strains with the coupled OXC-FRC pathway or OOR enzymes, examined catalytic site conservation by multiple sequence alignment, and performed AlphaFold-based structural prediction with Template Modeling (TM)-align scoring. Species with TM-scores >0.8 exhibited highly conserved folds, suggesting functional oxalate degradation capacity. These findings provide theoretical guidance for identifying probiotic candidates with oxalate-degrading activity and establish a framework for developing next-generation functional probiotics to alleviate kidney stone disease.
Insights
This study identifies probiotic strains with oxalate-degrading enzymes to combat kidney stones. These findings guide the development of new probiotics for treating calcium oxalate urolithiasis.
Area of Science:
- Bioinformatics
- Microbiology
- Urology
Background:
- Kidney stone disease, primarily calcium oxalate precipitation, has increasing global incidence.
- Current treatments for kidney stones have variable efficacy and high recurrence rates.
Purpose of the Study:
- To theoretically assess the oxalate-degrading potential of probiotic species.
- To identify probiotic candidates for developing functional probiotics to manage kidney stones.
Main Methods:
- Bioinformatic analysis using BLASTp homology searches on 38 probiotic species.
- Identification of key oxalate-degrading genes (OXC, FRC, OXDC, OOR).
- Structural prediction using AlphaFold and TM-align scoring for conserved enzyme folds.
Main Results:
- Seven strains identified with the coupled oxalyl-CoA decarboxylase (OXC) and formyl-CoA transferase (FRC) pathway.
- One strain identified with oxalate decarboxylase (OXDC), and three with oxalate oxidoreductase (OOR).
- High TM-scores (>0.8) indicated conserved enzyme structures, suggesting functional oxalate degradation.
Conclusions:
- This study provides a theoretical basis for selecting probiotics with oxalate-degrading capabilities.
- Identified strains serve as candidates for next-generation functional probiotics to alleviate kidney stone disease.
