Guanidine-producing enzymes and pathways in bacteria

• Applicant: Professor Dr. Jörg Steffen Hartig
• Subject Area: Biological and Biomimetic Chemistry
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 553554737

Guanidine has been discovered more than 160 years ago and was occasionally reported as metabolite in diverse organisms. Despite such early reports concerning its occurrence in nature and many uses in current technological applications, guanidine remains a blank spot on the metabolic map, since information about the occurrence and formation of this enigmatic compound in nature is scarce. My lab has recently contributed several discoveries of systems that sense, detoxify and assimilate guanidine in bacteria. The existence of widespread guanidine sensors and metabolizing pathways further illustrates that guanidine plays an as yet underappreciated role in nature. With this project, we set out to discover bacterial sources of guanidine in nature. We have recently discovered and characterized a novel pathway in Pseudomonads that degrades the plant antimetabolite canavanine to hydroxyguanidine. We have evidence that the metabolism of the wide-spread compound canavanine is intertwined with sensing and metabolizing free guanidine in bacteria. This project will investigate a novel canavanine degradation pathway resulting in the production of free guanidine in anaerobic bacteria that has been proposed to exist 65 years ago. For this purpose, the described Enterococcus species will be investigated regarding its ability to degrade and assimilate canavanine. In addition, an untargeted screen enriching microorganisms that produce free guanidine from canavanine will be carried out. Moreover, we will aim at the identification of novel degradation pathways of more common guanidine compounds such as arginine, agmatine, creatine and creatinine that result in the production of guanidine instead of the known dihydrolase pathways that yield the hydrolysis products urea or ammonia. The resulting enzymes and pathways from all three approaches will be studied in detail, broadening our general understanding of the metabolism of guanidine and its precursors.

• DFG Programme: Research Grants