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Wednesday, January 14, 2026

Not only toxic but also a nutrient: guanidine as a nitrogen source

Cyanobacteria convert light energy into chemical energy through photosynthesis and are becoming increasingly important for carbon-neutral biotechnology.
Photo Credit: André Künzelmann / UFZ

Scientific Frontline: "At a Glance" Summary

  • Main Discovery: Cyanobacteria possess the capability to actively absorb and catabolize guanidine (CH5N3) as their sole nitrogen source, refuting the prior scientific consensus that the compound acts exclusively as a toxic denaturant in these organisms.
  • Methodology: The study utilized an interdisciplinary approach combining genome analysis, molecular microbiology, biochemical binding assays, and simulation-based process analytics to map the complete metabolic pathway and regulatory networks.
  • Specific Mechanism: Uptake is facilitated by a newly identified, high-affinity ATP-binding cassette (ABC) transport system effective at low concentrations, while intracellular guanidine hydrolase converts the substrate into ammonium and urea for metabolic integration.
  • Key Regulation Detail: Gene expression for the transporter and hydrolase is controlled by a specific riboswitch that directly binds guanidine, functioning as a precise sensor to regulate uptake and trigger efflux systems if intracellular levels become toxic.
  • Ecological Context: These findings suggest that free guanidine is naturally available and constitutes an overlooked but integral component of global biogeochemical nitrogen cycles, providing a colonization advantage for cyanobacteria.
  • Future Application: The identified riboswitch mechanism offers a novel, cost-effective molecular tool for synthetic biology, enabling researchers to finely tune gene expression in cyanobacterial "green cell factories" by modulating guanidine levels.

A riboswitch as an important tool in sustainable biotechnology 

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 plays 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 (PNAS). The researchers shed light on the underlying mechanisms and the potential for a new tool for sustainable biotechnological applications. 

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 a 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. 

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 enters 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. 

"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. 

Published in journal: Proceedings of the National Academy of Sciences

TitleDeciphering guanidine assimilation and riboswitch-based gene regulation in cyanobacteria for synthetic biology applications

Authors: M. Amadeus Itzenhäuser, Andreas M. Enkerlin, Jan A. Dewald, Bihter Avşar, Ron Stauder, Hannes Halpick, Rosalie Schaale, Lisa M. Baumann, Noelia Fernandez Merayo, Thomas Maskow, Khaled A. Selim, Christina E. Weinberg, and Stephan Klähn

Source/CreditHelmholtz Centre for Environmental Research

Reference Number: btech011426_01

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