Fresh insights into how blue-green algae store CO₂

A closeup view of a CO₂ modified lysine residue (Lys-CO2) within the active site of a protein.

Cyanobacteria are “excellent little factories for developing CO₂-capture technologies” to help reduce greenhouse gas emissions, says Simon Fraser biochemist Dustin King. The problem, however, is that the cellular mechanisms it and other organisms use to sense and respond to CO₂ are a bit of a mystery.

King and his colleagues recently came up with a strategy to shed light on how these water-borne blue-green algae fix CO₂. They hope their research will lead to a better understanding of how cyanobacteria regulate their carbon capture system so others can

genetically engineer them to store even more CO₂. Genetically modified cyanobacteria are already being used at power stations and factories in some parts of the world to soak up CO₂ and King hopes his team’s work will help to boost their efficiency.

Cyanobacteria pull CO₂ from the atmosphere so they can use the carbon to create essential nutrients they need to live. They respond to low environmental CO₂ levels by actively concentrating it within specialized cellular compartments where it is directly added onto cellular metabolites. However, the mechanism through which cells ‘sense’ low CO₂ levels is unknown.

King proposes that CO₂ binds to particular proteins and changes their chemical properties. He reasons that this binding serves as a sort of CO₂ responsive chemical signal that the cell uses to regulate its CO₂-concentrating system. Artificially triggering that signal could lead to increased CO₂ storage.

But this process has been hard to study because CO₂ binds to proteins and then immediately falls off before scientists can detect it. This means they have no idea what part of the protein is involved in triggering the signal.

King and his colleagues, however, have come up with “a chemical trick” to see these elusive CO₂ binding sites on cyanobacteria proteins. In a paper published in July in Nature Chemical Biology, they show how they did it.

The first step was to use a molecule called isocyanic acid that mimics CO₂’s behaviour as it binds to a protein. “Isocyanic acid is able to modify the same parts on these proteins that CO₂ does, except, as opposed to CO₂, it forms a nice, stable adduct,” says King. “Where it gets a bit complicated is how do you now detect CO₂ binding using this analogue?”

The answer is to expose the protein-isocyanic acid adduct to CO₂. The CO₂ then competes with the isocyanic acid to modify the protein, which lessens the amount of isocyanic acid in the adduct.

In the process of competing, the CO₂ now forms a stable bond and the resulting adduct can be examined with a mass spectrometer to discover the binding site on the protein. King and his colleagues went a step further by using the synchrotron at the University of Saskatchewan’s Canadian Light Source to study the adduct in three dimensions.

University of Virginia chemist Ku-Lung Hsu calls it “an elegant and powerful method to study the lysine carboxylome.” As he writes in an accompanying commentary, “the ability to quantify Lys-CO₂ PTMs on proteins with amino acid resolution enables the assignment of CO₂-sensing function not only at the protein level but also to specific protein domains that mediate the response.”

King hopes his team’s discovery will provide a springboard for other, yet-to-be-discovered advances in human and environmental health. “Now we’re beginning to explore what effect changing the function of this protein has, not just in cyanobacteria but in other life forms,” he says.