Co-occurrence, toxicity, and biotransformation pathways of metformin and its intermediate product guanylurea: Current state and future prospects for enhanced biodegradation strategy

Abstract

Accumulation of metformin and its biotransformation product "guanylurea" are posing an increasing concern due to their low biodegradability under natural attenuated conditions. Therefore, in this study, we reviewed the unavoidable function of metformin in human body and the route of its release in different water ecosystems. In addition, metformin and its biotransformation product guanylurea in aquatic environments caused certain toxic effects on aquatic organisms which include neurotoxicity, endocrine disruption, production of ROS, and acetylcholinesterase disturbance in aquatic organisms. Moreover, microorganisms are the first to expose and deal with the release of these contaminants, therefore, the mechanisms of biodegradation pathways of metformin and guanylurea under aerobic and anaerobic environments were studied. It has been reported that certain microbes, such as Aminobacter sp. and Pseudomonas putida can carry potential enzymatic pathways to degrade the dead-end product "guanylurea", and hence guanylurea is no longer the dead-end product of metformin. However, these microbes can easily be affected by certain geochemical cycles, therefore, we proposed certain strategies that can be helpful in the enhanced biodegradation of metformin and its biotransformation product guanylurea. A better understanding of the biodegradation potential is imperative to improve the use of these approaches for the sustainable and cost-effective remediation of the emerging contaminants of concern, metformin and guanylurea in the near future.

Keywords: Biodegradation; Degradation pathway; Guanylurea; Metformin; Toxicity.