Abundance, Functional, and Evolutionary Analysis of Oxalyl-Coenzyme A Decarboxylase in Human Microbiota

Abstract

Oxalic acid and its oxalate salts have been linked to kidney stones and other health problems and about 80% kidney stones are made up of calcium oxalate. Oxalyl coenzyme A decarboxylase (OXC) is a key enzyme in the catabolism of oxalate. In this study, we performed bioinformatic and biochemical analysis of OXC. First, we mined the OXC sequences from a public protein database and collected 1396 putative OXC sequences. These sequences were widely spread and mainly distributed in Actinobacteria, Alphaproteobacteria, Gammaproteobacteria, and Betaproteobacteria and classified into seven clusters. The phylogenetic relationship and evolutionary rate of the 7 clusters showed that OXC are highly conserved. Second, the abundance of the different clusters of OXC was explored in 380 human microbiome datasets, which showed that OXCs in Cluster 1 were relatively high in the gut while OXCs in Clusters 2-4 were relatively enriched in the vagina. Third, we measured the activity of one OXC from Mycobacterium mageritense (OXCmm) in Cluster 3, in which there was no experimentally characterized enzymes. Mutation analysis showed that OXCmm shared the same active sites with the OXC from Oxalobacter formigenes. Taken together, this analysis provides a better insight into the distribution and catalysis of OXC and further potential alternative application of OXC active bacteria as probiotics in the management of kidney stone disease.

Probiotic Oxalate-Degrading Bacteria: New Insight of Environmental Variables and Expression of the oxc and frc Genes on Oxalate Degradation Activity

“…In the metagenomes of 660 subjects, oxc can be detected in 554 (84%) and frc in 581 (88%). According to Jiang et al [ 26 ], oxc can be found in a multitude of bacterial genomes and metagenomes, providing information about its presence, classification, and phylogenesis. Furthermore, they analyzed the enzyme’s abundance throughout the human microbiome, which is not limited to the gut.…”

“…It should be noted that the breakdown of oxalate in Lactobacilli and Bifidobacteria is specific to the genus and species of certain bacteria. In 2022, Jiang et al [ 26 ] studied the decomposition of oxalate in a wide range of human microbiota especially Bifidobacterium spp. They found that oxalate oxidase, decarboxylase, frc, and oxc are the key oxalate-degrading enzymes.…”

“…M77128) presented the highest nucleotide homology (56%) and amino acid similarity (identities, 47%; positives, 64%). Furthermore, most of the decarboxylase enzymes described to date, including the oxalyl-CoA decarboxylase of O. formigenes , present a conserved thiamine pyrophosphate (TPP)-binding region [ 26 ].…”

Probiotic Oxalate-Degrading Bacteria: New Insight of Environmental Variables and Expression of The Oxc and Frc Genes on Oxalate Degradation Activity

“…M77128) presented the highest nucleotide homology (56%) and amino acid similarity (identities, 47%; positives, 64%). Furthermore, most of the decarboxylase enzymes described to date, including the oxalyl-CoA decarboxylase of O. formigenes, present a conserved thiamine pyrophosphate (TPP)binding region [19].…”

A conserved oxalyl-coenzyme A decarboxylase in oxalate catabolism

“… 21 Coupling with formyl-coenzyme A transferase (FCR), OXC plays a critical role in oxalate degradation in bacteria. 22 Within the human gut microbiota OXCs have been found to be highly conserved and can be separated into seven clusters. 23 …”