Newly identified sensor protein influences metabolism in cyanobacteria and day-night rhythm

Cyanobacteria also have a day-night rhythm: the metabolism of these oldest forms of life on Earth adapts to the alternation of day and night, by a so-called circadian rhythm. Scientists at the University of Tübingen and the Max Planck Institute for Developmental Biology, as well as at the Universities of Göttingen, Rostock and Hannover, have now deciphered a novel signaling molecule and its receptor, which regulate this adaptation. Understanding the molecular basis of such processes, which oscillate with the so-called “circadian clock,” can help to understand the "internal clock" of other organisms, including humans. This regulates not only the day-night rhythm, but also numerous physiological processes, including our metabolism.

It was 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.

Dr. Khaled Selim and Professor Karl Forchhammer of the Interfaculty Institute for Microbiology and Infection Medicine (IMIT) and Max Planck Institute for Developmental Biology, and Principal Investigators at the University's Cluster of Excellence “Controlling Microbes to Fight Infections” (CMFI), together with colleagues, have now identified two responsible parties for this process: The protein SbtB, which is involved in regulating CO2 uptake - a process important for photosynthesis - and the chemical messenger c-di-AMP. The messenger molecule c-di-AMP is synthesized by almost all living bacteria and acts to inform the bacteria on their internal and/or external current cellular status. c-di-AMP is derived from the known nucleotide adenosine triphosphate (ATP), which is the basic building block of RNA. The research team around Dr. Selim and Prof. Forchhammer showed that the chemical messenger c-di-AMP is involved in the response of cyanobacterial cells to osmotic stress and also to the day-night rhythm via regulating glycogen metabolism.

It was already known that SbtB can regulate CO2 uptake. Dr. Selim and colleagues have now shown that it also regulates glycogen metabolism, suggesting a broader role in regulating central carbon metabolism.  When bound to the nucleotide c-di-AMP, SbtB interacts with an important enzyme for glycogen synthesis. Interestingly, the concentration of both c-di-AMP and SbtB peaks during the day and reaches its minimum during the night. Without the two substances, the cells would not be able to survive the night because they cannot build up sufficient glycogen stores during the day, according to the researchers. This suggests that c-di-AMP and SbtB regulate glycogen metabolism in the context of the natural day-night rhythm.

The researchers hypothesize that understanding the molecular mechanisms behind the central regulator SbtB can be used to manipulate carbon flux in cyanobacteria. This could make the production of useful products, such as the biodegradable plastic PHB or other feedstock chemicals more efficient and applicable on an industrial scale.

In the larger context, the findings improve our understanding not only of carbon metabolism in cyanobacteria, but also overall of the molecular basis of processes that interact with the circadian clock. This, in turn, could help understanding the day-night rhythms of other organisms - including humans. "One day, this may help us better understand why, for example, eating during the day and fasting at night protects us from diseases such as obesity and diabetes," says Khaled Selim.