Products Cited in Publications Worldwide Biochemical and genomic evidence for converging metabolic routes of metformin and biguanide breakdown in environmental Pseudomonads

Biochemical and genomic evidence for converging metabolic routes of metformin and biguanide breakdown in environmental Pseudomonads

Wissbroecker, Katie B; Zmuda, Anthony J; Karumanchi, Harsheeth; Niehaus, Thomas D

DOI: PMID:

Abstract

is commonly used to lower blood glucose levels and is one of the most widely used pharmaceuticals worldwide. Typical doses are high (0.5-2.0 g day-1) and the majority travels through the unabsorbed and enters the wastewater system. isn't removed by standard wastewater treatments and eventually enters freshwater systems, where it can form N-chloro-derivatives that are toxic to fish and human cells. Thus, is one of the most prevalent anthropogenic pollutants worldwide and there has been considerable interest in finding ways to remove it. We recently isolated Pseudomonads capable of growing on as the sole nitrogen source. We identified candidate genes involved in breakdown through genomic analyses informed by feeding studies. One candidate, a pair of genes that are located on ~80kb extra-genomic plasmids, was shown to encode a heteromeric Ni-dependent hydrolase that converts to guanylurea and dimethylamine. Metforminase activity of these gene products is now well established as our results confirm three recently published independent studies. Our isolated Pseudomonads also grow on biguanide, suggesting the existence of an additional breakdown enzyme. Another candidate gene located on the ~80kb plasmids was shown to encode an aminohydrolase that converts biguanide to guanylurea. Biguanide may arise through successive N-demethylations of or come from other sources. Our results suggest that the recent evolution of metforminase and biguanide hydrolase enzymes allow Pseudomonads to convert either or biguanide to guanylurea, which can be assimilated by existing pathways.

Keywords

; drug metabolism ; Pseudomonas ; hydrolase ; microbiome ; bacterial metabolism

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Biguanidehydrochloride

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