Researchers from CIIMAR and the University of Helsinki have discovered a new biochemical modification in natural cyanobacterial products, revealing an unprecedented ‘tool’ with promising applications in biotechnology and drug development.
The scientists have identified a previously unknown biochemical capability in cyanobacteria — microorganisms already recognised for producing a wide range of bioactive natural products used across sectors from shipping to pharmaceuticals.
The team has discovered that cyanobacteria can phosphorylate cyanobactins, a well-studied class of peptides with therapeutic potential.
This is the first time phosphorylation has been observed in this peptide family, revealing a new modification pathway that could expand opportunities for drug discovery and peptide engineering.
The potential of this discovery, although highly specific to the chemistry of natural products, is simple: it opens a whole new horizon of possibilities for marine biotechnology, especially for the development of future drugs.
The study, published in Nature Communications, has Raquel Castelo-Branco, a researcher in the CIIMAR Cyanobacterial Natural Products group, as its first author and was coordinated by the group’s principal investigator Pedro Leão, in collaboration with David Fewer of the University of Helsinki.
The new molecular “tool”
During her PhD at the University of Porto’s Faculty of Sciences, Castelo-Branco identified an unexpected feature while analysing cyanobacterial genomes from the LEGE (CIIMAR) and UHCC (University of Helsinki) collections: an enzyme containing an additional domain indicative of the ability to phosphorylate.
Castelo-Branco said: “The most fascinating thing was to see how a small genetic sequence identified in the genome led to the discovery of a new modification in cyanobactin.”
It is a rare enzyme that combines this new possibility of phosphorylation with the already known biosynthetic pathways of cyanobactins.
In short, this combination, never before observed, functions as a new module in the biotechnology toolbox.
It allows cyanobacteria themselves to produce phosphorylated molecules naturally and sustainably, without the need for laboratory chemistry.
“It is a perfect example of how genomics can reveal new biochemical functions hidden in nature,” explains the CIIMAR researcher.
Why is this important?
Phosphorylation is a very common biochemical process in cells, where a phosphate group is added to other molecules.
In proteins, this modification normally acts as a temporary regulatory mechanism, functioning as a ‘switch’ that turns their activity on or off depending on the cell’s needs.
However, the phosphorylation discovered in this study is different.
Instead of being a transient signal, it is a stable chemical modification, installed by a specialised enzyme during the biosynthesis of cyanobactins.
This phosphorylation is part of the final structure of the molecule itself, giving it unique properties and potentially new biological functions.
“Phosphorylation is a common modification in proteins, but extremely rare in the small specialised molecules we normally call ‘natural products’,” explains Castelo-Branco.
The fact that cyanobacteria do this transcends all scientific knowledge documented to date and opens the door to new strategies for the sustainable synthesis of phosphorylated compounds.
In the future, researchers plan to build a diverse library of peptides, which will be phosphorylated by this new enzyme, allowing them to explore its therapeutic potential in different areas, from oncology to regenerative medicine.
“We believe that this work could pave the way for the development of a library of phosphorylated peptides with anti-cancer, anti-bacterial and anti-viral potential."
“Nature continues to be an inexhaustible source of inspiration for creating more sustainable and innovative products,” concludes the CIIMAR researcher.