HMN 2026: How Cyanobacteria can utilize toxic guanidine as a nitrogen source

Guanidine is an organic compound primarily used as a denaturing reagent to disrupt the structures of proteins and nucleic acids. Together with partner institutions, scientists at the Helmholtz Centre for Environmental Research (UFZ) have demonstrated that cyanobacteria, which play a central role in global biogeochemical cycles, use guanidine as a nitrogen source.

The results were recently published in the Proceedings of the National Academy of Sciences. The researchers shed light on the underlying mechanisms and the potential for a new tool for sustainable biotechnological applications.

Cyanobacteria’s ecological and biotechnological significance

Cyanobacteria are key ecological players of global carbon and nitrogen cycles. They are also becoming increasingly important for carbon-neutral biotechnology. They could serve as green cell factories for light-driven and sustainable production of chemicals and fuels—a central pillar of the sustainable bioeconomy.

However, compared with other bacteria such as Escherichia coli, little is known about how cyanobacteria respond to environmental and internal signals, how their metabolism is coordinated, and how these regulatory mechanisms function.

Discovery of guanidine metabolism in cyanobacteria

The study, published by the UFZ in collaboration with Heinrich Heine University Düsseldorf and Martin Luther University Halle-Wittenberg, shows that cyanobacteria can actively absorb and break down guanidine (CH₅N₃) and even use it as their sole nitrogen source. This suggests that free guanidine is available in natural habitats and that the ability to use it is an advantage for colonization—even though guanidine has previously been regarded primarily as a toxic substance.

It was already known that guanidine is broken down in the cyanobacterial cell by guanidine hydrolase into ammonium and urea, which enter the metabolism through further reactions. The newly researched aspects include the uptake of guanidine as a nutrient via a newly discovered ATP-binding cassette (ABC) transport system, which recognizes guanidine with high affinity and ensures import into the cell even at low environmental guanidine concentrations.

At the same time, a special transport system (efflux system) that can also transport guanidine out of the cells protects them from excessive and therefore harmful concentrations. The enzymes and transport systems responsible for guanidine metabolism are widespread in cyanobacteria.

Implications for nitrogen cycles and biotechnology

“The study shows that guanidine is an integral part of nitrogen metabolism and must therefore also play a role in global biogeochemical cycles in nature,” says Dr. Stephan Klähn, molecular microbiologist at the UFZ and coordinator of the study.

To achieve this, the researchers combined genome analyses, molecular microbiology methods and biochemical binding studies with simulation-based process analyses and additionally investigated the regulation of guanidine metabolism. Genes for guanidine transporters and hydrolases are regulated at several levels, including via a riboswitch that reacts directly to guanidine binding.

Researchers are harnessing this mechanism for biotechnology: The riboswitch serves as a precisely controllable element that can be used to finely adjust gene expression in cyanobacteria by adding guanidine. This yields a molecular tool for the cost-effective control of biotechnological production processes suitable for a wide range of applications in synthetic biology.

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