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The Structure of an Oxalate Oxidoreductase Provides Insight into Microbial 2-Oxoacid Metabolism.

ABSTRACT: Thiamine pyrophosphate (TPP), a derivative of vitamin B1, is a versatile and ubiquitous cofactor. When coupled with [4Fe-4S] clusters in microbial 2-oxoacid:ferredoxin oxidoreductases (OFORs), TPP is involved in catalyzing low-potential redox reactions that are important for the synthesis of key metabolites and the reduction of N2, H(+), and CO2. We have determined the high-resolution (2.27 Å) crystal structure of the TPP-dependent oxalate oxidoreductase (OOR), an enzyme that allows microbes to grow on oxalate, a widely occurring dicarboxylic acid that is found in soil and freshwater and is responsible for kidney stone disease in humans. OOR catalyzes the anaerobic oxidation of oxalate, harvesting the low-potential electrons for use in anaerobic reduction and fixation of CO2. We compare the OOR structure to that of the only other structurally characterized OFOR family member, pyruvate:ferredoxin oxidoreductase. This side-by-side structural analysis highlights the key similarities and differences that are relevant for the chemistry of this entire class of TPP-utilizing enzymes.

SUBMITTER: Gibson MI

PROVIDER: S-EPMC4498597 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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The Structure of an Oxalate Oxidoreductase Provides Insight into Microbial 2-Oxoacid Metabolism.

Gibson Marcus I MI Brignole Edward J EJ Pierce Elizabeth E Can Mehmet M Ragsdale Stephen W SW Drennan Catherine L CL

Biochemistry 20150624 26

Thiamine pyrophosphate (TPP), a derivative of vitamin B1, is a versatile and ubiquitous cofactor. When coupled with [4Fe-4S] clusters in microbial 2-oxoacid:ferredoxin oxidoreductases (OFORs), TPP is involved in catalyzing low-potential redox reactions that are important for the synthesis of key metabolites and the reduction of N2, H(+), and CO2. We have determined the high-resolution (2.27 Å) crystal structure of the TPP-dependent oxalate oxidoreductase (OOR), an enzyme that allows microbes to ...[more]

PMID: 26061898

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Project description:For mammals, oxalate enters the body through the diet or is endogenously produced by the liver; it is removed by microbial oxalate metabolism in the gut and/or excretion in feces or urine. Deficiencies in any one of the these pathways can lead to complications, such as calcium oxalate urinary stones. While considerable research has been conducted on individual oxalate-degrading bacterial isolates, interactions between oxalate and the gut microbiota as a whole are unknown. We examined the reduction in oxalate excretion in a rat model following oral administration of fecal microbes from a mammalian herbivore adapted to a high oxalate diet or to fecal transplants consisting of two different formulations of mixed oxalate-degrading isolates. While all transplants elicited a significant reduction in oxalate excretion initially, the greatest effect was seen with fecal microbial transplants, which persisted even in the absence of dietary oxalate. The reduction in oxalate excretion in animals given fecal transplants corresponded with the establishment of diverse bacteria, including known oxalate-degrading bacteria and a cohesive network of bacteria centered on oxalate-degrading specialists from the Oxalobacteraceae family. Results suggested that the administration of a complete community of bacteria facilitates a cohesive balance in terms of microbial interactions. Our work offers important insights into the development of targeted bacteriotherapies intended to reduce urinary oxalate excretion in patients at risk for recurrent calcium oxalate stones as well as bacteriotherapies targeting other toxins for elimination. IMPORTANCE Oxalate is a central component in 80% of kidney stones. While mammals do not possess the enzymes to degrade oxalate, many gastrointestinal bacteria are efficient oxalate degraders. We examined the role of cohesive microbial networks for oxalate metabolism, using Sprague-Dawley rats as a model host. While the transplantation of oxalate-degrading bacteria alone to the Sprague-Dawley hosts did increase oxalate metabolism, fecal transplants from a wild mammalian herbivore, Neotoma albigula, had a significantly greater effect. Furthermore, the boost for oxalate metabolism persisted only in animals that received fecal transplants. Animals receiving fecal transplants had a more diverse and cohesive network of bacteria associated with the Oxalobacteraceae, a family known to consist of specialist oxalate-degrading bacteria, than did animals that received oxalate-degrading bacteria alone. Our results indicate that fecal transplants are more effective at transferring specific functions than are microbial specialists alone, which has broad implications for the development of bacteriotherapies.

Dataset Information

The Structure of an Oxalate Oxidoreductase Provides Insight into Microbial 2-Oxoacid Metabolism.

Publications

The Structure of an Oxalate Oxidoreductase Provides Insight into Microbial 2-Oxoacid Metabolism.

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