Roles of second messengers in the regulation of cyanobacterial physiology: the carbon-concentrating mechanism and beyond

Abstract

Second messengers are a fundamental category of small molecules and ions that are involved in the regulation of many processes in all domains of life. Here we focus on cyanobacteria, prokaryotes playing important roles as primary producers in the geochemical cycles due to their capability of oxygenic photosynthesis and carbon and nitrogen fixation. Of particular interest is the inorganic carbon-concentrating mechanism (CCM), which allows cyanobacteria to concentrate CO2 near RubisCO. This mechanism needs to acclimate toward fluctuating conditions, such as inorganic carbon availability, intracellular energy levels, diurnal light cycle, light intensity, nitrogen availability, and redox state of the cell. During acclimation to such changing conditions, second messengers play a crucial role, particularly important is their interaction with the carbon control protein SbtB, a member of the PII regulator protein superfamily. SbtB is capable of binding several second messengers, uniquely adenyl nucleotides, to interact with different partners in a variety of responses. The main identified interaction partner is the bicarbonate transporter SbtA, which is regulated via SbtB depending on the energy state of the cell, the light conditions, and different CO2 availability including cAMP signaling. The interaction with the glycogen branching enzyme, GlgB, showed a role for SbtB in the c-di-AMP-dependent regulation of glycogen synthesis during the diurnal life cycle of cyanobacteria. SbtB has also been shown to impact gene expression and metabolism during acclimation to changing CO2 conditions. This review summarizes the current knowledge about the complex second messenger regulatory network in cyanobacteria, with emphasis on carbon metabolism.

Diurnal rhythm causes metabolic crises in the cyanobacterial mutants of c-di-AMP signalling cascade

“…Nevertheless, our data revealed a broad range of cellular processes that are subjected to c-di-AMP regulation, likely through binding to yet unidentified transcription factor(s) or small RNAs to propagate the c-di-AMP-mediated responses. In sum all these processes might lead to the observed lethality of the c-di-AMP deficient ΔdacA mutant under diurnal growth, while the diurnal lethality of ΔsbtB seems to be restricted to carbon metabolism (Selim et al 2021, Mantovani et al 2022& 2023a.…”

“…Therefore, night phases require a metabolic switch to heterotrophic-like carbon catabolism, which includes glycogen catabolism mainly via the oxidative pentose-phosphate (OPP) pathway (Gründel et SbtB, a small regulatory protein belonging to the PII signaling superfamily (Forchhammer et al 2022), is encoded in an operon together with the low Ci-induced sodium-dependent bicarbonate transporter SbtA (Selim et al 2018, Forchhammer andSelim 2020). Similar to canonical PII proteins (Lapina et al 2018, Selim et al 2019& 2020a, SbtB binds the adenine nucleotides ATP and ADP, but in contrast to these, it also binds AMP, cAMP and c-di-AMP (Selim et al 2018(Selim et al & 2021, thus combining the cell's energy status with second messenger signaling, which directly influences the SbtA-B complex formation (Selim et al 2023) and many other processes related to Ci acclimation (Mantovani et al 2022(Mantovani et al , 2023a(Mantovani et al & 2023b. Under low Ci conditions, intracellular AMP levels rise, thus leading to a strong SbtA-B complex in which SbtB serves as plug-like structure to prevent HCO3 -leakage (Haffner et al 2023.…”

“…Furthermore, cyanobacteria evolved an intricate circadian clock to sense and anticipate to consecutive day-night cycles (Welkie et al 2019). In addition, the second messenger nucleotides guanosine penta- and tetraphosphate [(p)ppGpp] as well as cyclic di-adenosine monophosphate (3′,5′-c-di–adenosine 5′-monophosphate; hereafter c-di-AMP) have recently been shown to be involved in regulating cyanobacterial diurnal lifestyle (Hood et al 2016, Puszynska and O’Shea 2017, Rubin et al 2018, Mantovani et al 2023a). The latter by regulation glycogen synthesis via the PII-like protein SbtB (Selim et al 2021).…”

“…Recently, c-di-AMP, one of the newly discovered second messengers, turned out to play important roles in cyanobacterial acclimation mechanisms (Mantovani et al 2023a). In Firmicutes, c-di-AMP is known to control cell wall integrity and osmotic homeostasis by regulating osmolyte and K + and Mg 2+ ion transporters (Stülke and Krüger 2020, Yin et al 2020).…”

The second messenger c-di-AMP controls natural competence via ComFB signaling protein

“…Second messengers are small molecules involved in regulating many processes in all kinds of organisms (Yoon & Waters 2021). Cyclic di-AMP is one of the recently discovered di-nucleotide-type second messengers only present in prokaryotes (Stülke & Krüger 2020; He et al 2020; Yin et al 2020; Mantovani et al 2023a). Its functions have been mainly studied in firmicutes, where it plays an important role in osmo-adaptation by controlling potassium homeostasis and influencing transcription of genes related to osmosis and cell wall metabolism (Stülke & Krüger 2020; He et al 2020; Yin et al 2020; Herzberg et al 2023; Nelson et al 2013; Ren & Patel 2014).…”