An Acyl Activating Enzyme (AAE) 3 homolog encodes an oxalyl -CoA synthetase in Bradysia coprophila

Authors: CELA, ALDONA - Baylor College Of Medicine; WANG, FAYNA - Baylor College Of Medicine; GUEHRIA, HANNAH - Baylor College Of Medicine; Nakata, Paul

Submitted to: Protein Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/13/2026
Publication Date: 5/13/2026
Citation: Cela, A., Wang, F.S., Guehria, H., Nakata, P.A. 2026. An Acyl Activating Enzyme (AAE) 3 homolog encodes an oxalyl -CoA synthetase in Bradysia coprophila. Protein Science. 35(5). Article e70549. https://doi.org/10.1002/pro.70549.
DOI: https://doi.org/10.1002/pro.70549

Interpretive Summary: Oxalic acid is commonly produced by organisms to provide some sort of selective advantage that benefits their survival. Unregulated exposure or prolonged production of this acid; however, can lead to multiple physiological problems. Most organisms have a way of breaking down oxalate to prevent the development of any physiological problems. Yet, no mechanism of oxalate breakdown has been identified in animals. In this study we identify the first enzyme, from any animal, capable of catalyzing the first step in oxalate breakdown. We searched the animal database of gene sequences, using bioinformatics, for a gene that matched a known oxalate degradative gene that we previously identified in plants. We identified a gene in the fungal gnat (insect) that contained a sequence similar to the plant oxalate degradative gene. We used molecular biology to synthesize and express this insect gene in bacteria. We purified the enzyme and tested it for oxalate breakdown activity using biochemical methods. We found that the enzyme did indeed possess the same oxalate breakdown activity as the one we previously identified in plants. Three-dimensional modeling predicted that this newly identified fungal gnat enzyme folded into a 3D structure that resembled the plant enzyme. It is our hope that such information will be useful in developing strategies to combat physiological oxalate-related problems such as kidney stone formation in animals.

Technical Abstract: Although oxalate is common in nature our understanding of its metabolism remains incomplete. To our knowledge no oxalate catabolic activity has been identified in any animal. In this study we identify the first oxalate degradative activity in animals. We show that the Bradysia coprophila genome contains an acyl-activating enzyme 3 (BcAAE3) that is capable of catalyzing the conversion of oxalate to oxalyl-CoA. Based on our results, we propose that the oxalyl-CoA synthetase activity encoded by BcAAE3 catalyzes the first step in a CoA-dependent pathway of oxalate degradation. In addition, our findings extend the importance of the CoA-dependent pathway of oxalate degradation to a wide range of organisms from simple microbes to complex animals.