# From lab reagent to metabolite: the riboswitch ligand guanidine as a relevant compound in bacterial physiology

## TL;DR

This review explores how riboswitch research revealed guanidine as a biologically significant compound in bacteria, highlighting its roles as a nutrient and stressor.

## Contribution

The paper synthesizes recent findings on guanidine's physiological roles and identifies gaps in understanding its natural sources and broader biological relevance.

## Key findings

- Certain bacteria assimilate guanidine as a nitrogen source using specific enzymes and transporters.
- Guanidine riboswitches are often linked to efflux transporters, suggesting guanidine may act as a stressor.
- Few bacterial guanidine-producing enzymes are known, despite hints that E. coli may produce it.

## Abstract

Efforts of the last 20 years in validating novel riboswitches led to the identification of numerous new motifs recognizing compounds with well-established biological functions. However, the recent characterization of widespread classes of riboswitches binding the nitrogen-rich compound guanidine raised questions regarding its physiological significance that has so far remained elusive. Recent findings established that certain bacterial species assimilate guanidine as a nitrogen source via guanidine-specific enzymes and transporters and that complete ammonium oxidizers can use it as a sole source of energy, reductant, and nitrogen. The frequent association of guanidine riboswitches with genes encoding guanidine efflux transporters also hints that bacteria may experience the burden of guanidine as a stressor during their lifestyle. A major gap in understanding the biology of guanidine resides in its natural source. While metabolic pathways responsible for guanidine synthesis were defined in plants, only a few guanidine-producing enzymes have been identified in bacteria, despite indications that the model organism E. coli may produce guanidine. This review summarizes how riboswitch research unveiled guanidine as an important compound in living organisms and the recent findings advancing our knowledge of guanidine biology. We also highlight open questions that will orient future research aiming at gaining further insights into the biological relevance of guanidine.