Cyanobacteria can fix and convert CO2 into valuable industrial products such as biodegradable plastics (polyhydroxybutyrate) or other feedstock chemicals. In their study published in the journal PNAS, CMFI PI Khaled Selim and team clarify molecular principles that allow manipulation of CO2 flux in cyanobacteria and the molecular mechanisms involved. An important role here is played by the circadian clock, which controls molecular mechanisms in cyanobacteria.
Cyanobacteria are ancient organisms that started oxygenic photosynthesis approximately 3 billion years ago and thereby enriched Earth’s atmosphere with oxygen. Moreover, they fix atmospheric CO2 to form organic molecules such as carbohydrates and glucose. To guarantee sufficient intracellular carbon supply, cyanobacteria evolved highly efficient carbon uptake systems, termed carbon concentrating mechanisms (CCM). When the carbon supply is in excess, they make use of it by producing reserve biopolymers such as glycogen and polyhydroxybutyrate. The latter can be used as biodegradable plastic. Cyanobacteria count for approximately 15 % of the global photosynthetic production and represent an ideal source for biotechnological applications.
As CO2 fixation is closely linked to the photosynthetic activity, it is influenced by the natural alternation of day-night cycles. Therefore, cyanobacteria such as the unicellular model organism Synechocystis sp. require a tight regulation of the CO2 fixation in response to diurnal rhythms. It is already known that cyanobacteria adjust their metabolism during the transition from day to night using an oscillating circadian clock. During the day, they use light energy to perform photosynthesis and store fixed carbon in the form of glycogen. During the night, glycogen is broken down to generate energy, allowing cyanobacteria to survive night periods of darkness. Recently, we discovered a new protein that regulates the intake of CO2 into the cell by controlling one of the carbon uptake systems, namely, SbtA. This protein is known as SbtB.
The researchers provide through thier study insights into how SbtB regulates the activity of SbtA not only based on the intracellular carbon supply but also in response to the natural diurnal rhythms. SbtB senses the energy state of the cell by binding the energy carrier molecules ATP, ADP, and AMP - a kind of battery for the cell. SbtB in the AMP bound state is able to interact with SbtA and thereby regulate its transport activity. However, the transition of SbtB from the ATP- through the ADP- to the AMP-bound state was poorly understood. We found that SbtB exhibits atypical diphosphohydrolase (apyrase) activity to hydrolyze ATP and ADP into AMP successively, generating a condition that favors tight interaction between SbtA and SbtB. We proved that the SbtB apyrase activity is regulated in response to the alternation of day-night cycles via a redox sensing C-terminal extension, termed R-loop (i.e. Redox regulated loop). During the night, the R-loop of SbtB is oxidized, which induces the apyrase activity and thereby to the AMP-bound state blocking the carbon uptake activity due to the absence of photosynthesis in the night. By contrast, in the day phase the R-loop becomes reduced, which inhibits the apyrase activity of SbtB keeping the carbon uptake in the active state. Furthermore, we revealed that the redox-state of SbtB is regulated by the thioredoxin TrxA, which is able to reduce the R-loop of SbtB during the day phase.
In light of their ability to fix CO2 and transform it into valuable products such as biodegradable plastics (polyhydroxybutyrate) or other feedstock chemicals, cyanobacteria are therefore excellent model organisms for various biotechnological applications. By elucidating the molecular bases behind the activity of the central carbon regulator SbtB, our work provides a framework to manipulate carbon flux in cyanobacteria for more efficient carbon fixation on an industrial scale. Moreover, not only our findings improve our understanding of carbon metabolism in cyanobacteria but also of the molecular machineries underlying processes that are regulated via the circadian clock. This could have implications for other organisms - including humans. For an even broader perspective, knowing more about the evolutionary mechanisms of cyanobacteria as one of the oldest organisms on Earth offers clues to very early life on the planet.
(Authors: Michael Haffner & Khaled Selim)
Selim KA, Haffner M, Mantovani O, Hartmann MD. Carbon signaling protein SbtB possesses atypical redox-regulated apyrase activity to facilitate regulation of bicarbonate transporter SbtA. Proc. Natl. Acad. Sci. 120(8): e2205882120. (2023) doi: 10.1073/pnas.2205882120.
Dr. Khaled Selim
Interfaculty Institute of Microbiology and Infection Medicine
Auf der Morgenstelle 28
Tel.: +49 7071 29-74627
Nature - Behind the paper