Dr. Martin St. Maurice
Marquette University, Department of Biological Sciences
Tuesday, November 21, 2023 - 11:00am
Earth Sciences 3087
Guanide and biguanide compounds are commonly found in fertilizers, fuel propellants and pharmaceuticals, with the most notable example being the biguanide drug metformin. Metformin is the fourth most prescribed drug on the planet and is entering wastewater treatment plants at an alarming rate, with no clear sense of how it is being degraded by microorganisms. The recent discovery of bacterial operons controlled by guanidinium-binding riboswitches suggests that bacteria might contribute to the environmental degradation of guanide and biguanide compounds. The genes encoding the enzymes urea carboxylase and allophanate hydrolase are present in operons controlled by the guanidine-I riboswitch. These enzymes are known to function in tandem to facilitate the ATP-dependent hydrolysis of urea to ammonia and carbon dioxide, but we and others have shown that urea carboxylase prefers guanidine over urea. We have demonstrated that the combined activities of urea carboxylase and allophanate hydrolase are insufficient to catalyze guanidine degradation and that an additional heterodimeric enzyme, previously annotated as a “urea carboxylase-associated protein”, is required in this pathway. This enzyme acts as a carboxyguanidine deiminase (CgdAB) to hydrolyze carboxyguanidine to allophanate for subsequent degradation by allophanate hydrolase. CgdAB belongs to a large, functionally uncharacterized family of metalloenzymes, suggesting that it utilizes a unique iminohydrolase mechanism. Interestingly, guanidine is a very poor substrate for the fungal urea carboxylases and, notably, fungi also do not encode the genes for CgdAB. This suggests that the guanidine degradation pathway has evolved uniquely among the prokaryotes to allow them to degrade guanidine for use as a nitrogen source. This work contributes new insights into how biguanide compounds are funneled into biodegradative pathways, and provides a gateway to better understanding how nitrogen-rich medicines, insecticides, fertilizers, and explosives are environmentally degraded.
Dept of Cell and Systems Biology