Next Article in Journal
Dynamic Equilibrium of Protein Phosphorylation by Kinases and Phosphatases Visualized by Phos-Tag SDS-PAGE
Previous Article in Journal
Insights into the Regulation of the Mitochondrial Inheritance and Trafficking Adaptor Protein Mmr1 in Saccharomyces cerevisiae
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

Protein Phosphorylation Nexus of Cyanobacterial Adaptation and Metabolism

Department of Biology/Microbiology, South Dakota State University, Brookings, SD 57007, USA
*
Authors to whom correspondence should be addressed.
Kinases Phosphatases 2024, 2(2), 209-223; https://doi.org/10.3390/kinasesphosphatases2020013
Submission received: 14 May 2024 / Revised: 12 June 2024 / Accepted: 18 June 2024 / Published: 20 June 2024

Abstract

:
Protein phosphorylation serves as a fundamental regulatory mechanism to modulate cellular responses to environmental stimuli and plays a crucial role in orchestrating adaptation and metabolic homeostasis in various diverse organisms. In cyanobacteria, an ancient phylum of significant ecological and biotechnological relevance, protein phosphorylation emerges as a central regulatory axis mediating adaptive responses that are essential for survival and growth. This exhaustive review thoroughly explores the complex terrain of protein phosphorylation in cyanobacterial adaptation and metabolism, illustrating its diverse forms and functional implications. Commencing with an overview of cyanobacterial physiology and the historical trajectory of protein phosphorylation research in prokaryotes, this review navigates through the complex mechanisms of two-component sensory systems and their interplay with protein phosphorylation. Furthermore, it investigates the different feeding modes of cyanobacteria and highlights the complex interplay between photoautotrophy, environmental variables, and susceptibility to photo-inhibition. The significant elucidation of the regulatory role of protein phosphorylation in coordinating light harvesting with the acquisition of inorganic nutrients underscores its fundamental importance in the cyanobacterial physiology. This review highlights its novelty by synthesizing existing knowledge and proposing future research trajectories, thereby contributing to the deeper elucidation of cyanobacterial adaptation and metabolic regulation through protein phosphorylation.

1. Introduction

Cyanobacteria, recognized as ubiquitous microorganisms proficient in oxygenic photosynthesis, thrive across varied ecological habitats, encompassing freshwater ecosystems to extreme environments [1]. Their remarkable capacity to acclimate to dynamic environmental fluctuations underscores the necessity of sophisticated regulatory mechanisms that modulate cellular responses [2]. In this context of regulatory processes, protein phosphorylation assumes paramount importance as a fundamental post-translational modification that is crucial for signal transduction and metabolic regulation [3]. While protein phosphorylation has been extensively examined in eukaryotic systems, the investigation of this process in prokaryotes, particularly cyanobacteria, has provided new insights into their adaptive mechanisms and metabolic interactions [4]. As photoautotrophic microorganisms, cyanobacteria rely predominantly on light as their principal energy source, presenting them with intricate challenges in balancing energy procurement and metabolic needs [5]. This dependence on photoautotrophy demands adaptive responses to environmental variables such as the light intensity, spectral composition, and accessibility of inorganic nutrients [6]. Of particular note, the phototrophic lifestyle makes cyanobacteria susceptible to photoinhibition, highlighting the essential importance of inorganic nutrients in alleviating oxidative stress and maintaining cellular viability [7].
Traditionally, inquiries into protein phosphorylation in prokaryotes have primarily emphasized the formation of phosphate monoesters with amino acid residues containing hydroxyl groups, with protein acyl phosphates and amido phosphates relegated to roles as intermediates in enzymatic catalysis [8]. Nevertheless, pioneering studies have shed light on the crucial involvement of these phosphorylation variants in sensory transduction processes mediated by two-component sensor systems [9]. These systems include conserved protein families such as histidine protein kinases and response regulators [10]. This paradigmatic shift accentuates the imperative to reassess the dynamics of protein phosphorylation in cyanobacteria to precisely delineate their adaptive responses and metabolic coordination [11]. In this thorough investigation, we explore the complex interrelationships between protein phosphorylation, cyanobacterial adaptation, and metabolism. Our aim is to comprehensively elucidate the various forms of protein phosphorylation in cyanobacteria and their crucial role in orchestrating adaptive responses to environmental stimuli by synthesizing fundamental studies and recent advances [12]. Through the careful synthesis of the existing literature and innovative perspectives, this review seeks to improve our understanding of the regulatory modalities that control cyanobacteria’s adaptation and metabolism [13]. By clarifying unexplored research directions and potential biotechnological implications, this undertaking aims to expand the breadth of scientific research and practical applications in this area [14].

2. Indications of Protein Phosphorylation: Forms and Functions

Protein phosphorylation, a crucial post-translational modification, plays a critical role in regulating cellular signaling cascades and adaptive responses [15]. Within cyanobacteria, the prevalence and importance of protein phosphorylation have been revealed through various experimental approaches, revealing the diverse forms and functions associated with this phenomenon [16]. Experimental strategies, including in vivo labeling techniques with [32P]-orthophosphate, have revealed a diverse range of phosphoproteins in various cyanobacterial taxa [17]. However, it is important to recognize the intrinsic limitations of the method as it only finds common phosphoproteins that have undergone monoester phosphorylation (Figure 1). Furthermore, the possibility of simultaneously identifying alternative protein modifications such as adenylation and ADP-ribosylation highlights the complex regulatory framework that controls the protein dynamics in these extraordinary photosynthetic organisms. This intricate interplay of post-translational modifications demonstrates how sophisticated and complex the cellular signaling mechanisms of cyanobacteria have become, enabling their remarkable ecological success and adaptability [18,19].
Supplementary studies using in vitro methods with [γ-32P] ATP have extended our understanding of the protein phosphorylation dynamics [20]. These assays, employing cell-free extracts of various cyanobacterial strains, have elucidated a plethora of phosphorylated polypeptides, underscoring their broad phosphorylation capacity that goes beyond the scope of in vivo observations [21]. However, the judicious interpretation of these results is imperative, as the indiscriminate phosphorylation of specific polypeptides can lead to spurious artifacts without authentic physiological relevance. In addition, detailed studies have elucidated the phosphorylation of specific proteins in cyanobacterial cells [22]. For example, studies have found the phosphorylation of thylakoid proteins at serine or threonine residues, highlighting the critical role of phosphorylation in modulating photosynthetic mechanisms [23]. Additionally, light-dependent phosphorylation phenomena have been recorded for diverse polypeptides associated with cyanobacterial membranes and phycobilisome fractions, accentuating the nuanced connection between the protein phosphorylation dynamics and environmental stimuli [24].
Overall, the manifestations of protein phosphorylation in cyanobacteria highlight its diverse forms and functions, encompassing regulatory mechanisms in photosynthesis and broader cellular adaptation processes [25]. Continued investigation into these phenomena has the potential to improve our understanding of the cyanobacterial physiology and its relevance in various biological contexts.

3. Historical Perspective: Early Studies on Protein Phosphorylation in Prokaryotes

Early investigations into protein phosphorylation in prokaryotes laid the foundation for our understanding of this crucial post-translational modification [26]. Initially, research focused primarily on the formation of phosphate monoesters involving hydroxyl-containing amino acid residues. The prevailing notion was that protein acyl-phosphates and amido phosphates were mere intermediate products of enzymatic catalysis [27]. However, pioneering studies gradually unveiled the significance of these forms of protein phosphorylation beyond enzymatic processes. Recent findings have elucidated the essential role of protein phosphorylation in prokaryotic organisms, particularly in facilitating sensory transduction mechanisms [28]. This involvement is prominently manifested through the coordinated effect of two-component sensory systems. These systems involve evolutionarily conserved histidine protein kinase and response regulator families, facilitating adaptive responses to environmental stimuli [29]. The clarification of these intricate signaling pathways initiated a paradigmatic transition in the understanding of the prokaryotic physiology and highlighted the complexity and refinement of their regulatory machinery [30]. Furthermore, the study of protein phosphorylation in prokaryotes has disrupted traditional paradigms in microbial metabolism [31]. It has illuminated the intricate interplay between cellular signaling cascades and metabolic pathways, thereby emphasizing the integration of multifaceted cellular processes. These revelations have not only expanded our understanding of prokaryotic biology but also provided a framework for the investigation of analogous regulatory mechanisms in higher organisms [32]. As shown in Figure 2, after some consideration, the first studies of protein phosphorylation in prokaryotes established a foundational framework elucidating the intricacies of cellular regulation and adaptation [33]. These studies epitomize the iterative progress inherent in scientific research, with preliminary observations serving as catalysts for in-depth exploration, subsequently refining our comprehension of fundamental biological phenomena.

4. Two-Component Sensory Systems and Protein Phosphorylation

Two-component sensory systems, comprising histidine protein kinases (HKs) and response regulators (RRs), play an indispensable role in the acclimation of bacteria to a wide range of environmental stimuli [34]. These systems have been thoroughly studied in various bacterial taxa, and their crucial contributions to cellular responses to various environmental challenges have been elucidated [35]. In particular, cyanobacteria exhibit genetic elements encoding proteins analogous to HKs and RRs, underscoring their involvement in perceiving and reacting to environmental stimuli [36]. Investigations have revealed the presence of genes in cyanobacteria such as Synechococcus sp. PCC 7002 and Synechocystis sp. PCC 6803 bearing notable sequence resemblances to established histidine protein kinases (HKs) and response regulators (RRs) [37]. For instance, in Synechococcus sp. PCC 7002, an open reading frame (ORF) located downstream of the petH gene exhibits similarity to diverse response regulators [38]. Furthermore, a mutant strain of Synechocystis sp. PCC 6803, displaying resistance to diuron herbicide, demonstrates sequence homology to the histidine protein kinase PhoR identified in Bacillus subtilis. Further genomic exploration of cyanobacteria has unveiled genes such as sasA, ssrA, and SUB in Synechococcus sp. PCC 7942, encoding proteins that bear a resemblance to histidine kinases (HKs) and response regulators (RRs) [39]. An intriguing observation among these findings pertains to SasA, a protein exhibiting structural homology with histidine kinases identified in Escherichia coli [40]. Remarkably, SasA exhibits autophosphorylation activity, suggesting a conserved mechanistic role, similar to its counterparts in E. coli [41]. Additionally, it is observed that the response regulators in cyanobacteria often harbor supplementary domains, exemplified by the extra N-terminal domain identified in SsrA. This structural complexity contributes to the intricacy of the regulatory mechanisms governing cellular responses [42]. The identification of a histidine protein kinase and response regulator pair encoded on the endogenous plasmid in Synechococcus sp. PCC 7942 serves to underscore the fundamental significance of these systems in the cyanobacterial physiology [43]. Moreover, an open reading frame (ORF) located upstream of the PSI gene psaE in cyanobacteria exhibits sequence similarity with the response regulator PhoP of B. subtilis, albeit transcribed from the antisense strand [44]. Protein phosphorylation, a unbiquitous post-translational modification, intricately regulates the functioning of two-component sensory systems in cyanobacteria [45]. The autophosphorylation of histidine residues within sensor kinases, followed by subsequent phosphotransfer to response regulators, constitutes a pivotal step in signal transduction cascades. Phosphorylation-induced conformational alterations in response regulators modulate their interactions with target molecules, thereby fine-tuning gene expression profiles [46].
In summary, the examination of two-component sensory systems alongside protein phosphorylation in cyanobacteria elucidates the intricate mechanisms governing environmental sensing and adaptive responses [47]. Further scientific investigations offer the potential to enhance our understanding of the bacterial physiology and uncover novel targets with implications for both biotechnological and therapeutic applications.

5. Central Nutritional Mode of Cyanobacteria: Photoautotrophy

Cyanobacteria epitomize a diverse assemblage of microorganisms capable of harnessing solar energy through photoautotrophy, a fundamental nutritional strategy that positions them as primary producers in various ecosystems and pivotal agents in global carbon and nitrogen fluxes [48]. Although the principle of photoautotrophy is firmly established, recent research advances have led to new insights that elucidate the intricate molecular underpinnings governing this metabolic pathway in cyanobacteria [49]. Recent discoveries in the realm of molecular biology have illuminated the intricate network of proteins governing the process of photoautotrophy in cyanobacteria [25]. This metabolic pathway involves a series of precisely coordinated enzymatic reactions aimed at assimilating carbon dioxide (CO2) and procuring essential nutrients that are vital for cellular growth and metabolic processes [50]. Key enzymes such as ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) play a pivotal role in catalyzing the conversion of CO2 into organic molecules via the Calvin–Benson cycle [51]. Furthermore, the efficient utilization of inorganic nutrients, encompassing nitrogen, phosphorus, and sulfur, is meticulously regulated to ensure optimal metabolic functioning and sustained cellular proliferation [52]. The photoautotrophy of cyanobacteria is characterized by its remarkable ability to acclimate to dynamic environmental fluctuations [53]. These microorganisms demonstrate exceptional plasticity in their metabolic pathways, facilitating their proliferation across a spectrum of habitats spanning from aqueous ecosystems to extremely thermal and arid locales [54]. Investigations have elucidated the intricate molecular mechanisms governing this adaptability, emphasizing the indispensable involvement of protein phosphorylation in orchestrating cellular responses to environmental stimuli [55]. Additionally, the scrutiny of cyanobacterial genomes has revealed a plethora of newly discovered genes encoding proteins involved in photoautotrophic metabolism. Comparative genomics, coupled with functional analyses, has provided unprecedented insights into the evolutionary mechanisms governing the diverse photoautotrophic strategies of cyanobacteria [56]. These findings underscore the imperative to integrate genomic, biochemical, and physiological methodologies to unravel the intricate complexities of cyanobacterial photoautotrophy [57].
In conclusion, the pivotal nutritional strategy of cyanobacteria, namely photoautotrophy, epitomizes a compelling paradigm of metabolic plasticity and adaptability to environmental fluctuations. Through elucidating the intricate molecular mechanisms underpinning photoautotrophic metabolism, we stand to glean invaluable insights into the ecological prominence and biotechnological prospects of these primordial microorganisms. Future research efforts aimed at unraveling the complexities of cyanobacterial photoautotrophy hold promise in unveiling novel therapeutic avenues, harnessing biotechnological innovations, and devising strategies to ameliorate environmental perturbations.

6. Protein Phosphorylation-Mediated Chromatic Adaptation in Cyanobacteria

Chromatic adaptation represents a fundamental mechanism utilized by cyanobacteria to finely tune their photosynthetic apparatus in response to fluctuations in light parameters, thereby maximizing their photosynthetic output [58]. Key to this adaptive process are phycobiliproteins, comprising phycocyanin, phycoerythrin, and allophycocyanin, which act as the main light-harvesting antenna pigments associated with photosystem II (PSII) [59]. Extensive investigations have unveiled the intricate molecular framework governing chromatic adaptation, with a particular emphasis on its modulation in accordance with alterations in the spectral characteristics of incident light [60]. Emerging research has revealed the involvement of a phosphorylation cascade, under the influence of photo-perception, in the regulation of complementary chromatic adaptation. This cascade encompasses histidine protein kinases, exemplified by NR, and potentially myosin light-chain kinases, which oversee the phosphorylation dynamics of pivotal proteins implicated in chromatic adaptation [61,62]. Despite the ongoing debate regarding the precise functional contributions of these kinases, their participation in the modulation of chromatic adaptation underscores the intricate regulatory intricacies inherent in this physiological process [63]. Furthermore, the phenomenon of inverse chromatic adaptation, delineated by the discernible augmentation in the abundance of photosystem I (PSI) components upon exposure to PSII light, has been extensively demonstrated in cyanobacterial studies [64]. It is also necessary to acknowledge the critical role of the KaiABC circadian system, a phosphorylation-dependent process fundamental to cyanobacteria metabolism. Although some seminal papers can be cited, this essential mechanism is overlooked. Careful in vivo labeling experiments have elucidated the enhanced phosphorylation of specific polypeptides, particularly a 19 kDa protein within the phycobilisome fraction, under photosystem II (PSII) illumination conditions. However, the complex dynamics of the kaiABC system, which governs the circadian rhythms that determine cyanobacteria’s physiology and metabolism, remain unaccounted for. This oversight represents a significant gap in the comprehensive understanding of the complex regulatory networks underlying cyanobacterial metabolism [65]. This phosphorylation event, particularly targeting tyrosine residues within P-phycocyanin, has been conjectured to exert a pivotal influence in a photoreceptor mechanism and orchestrate protracted alterations in the composition of photosynthetic complexes [66]. Significantly, through the sequence analysis of DNA fragments from cyanobacteria encoding phycobiliprotein rod components, potential candidates for phosphatases implicated in dephosphorylation processes have been identified [67]. These phosphatases, demonstrating homology to cytosolic acid phosphatases, may serve as critical regulators in modulating the phosphorylation states of essential proteins involved in chromatic adaptation. The comprehensive understanding of the protein phosphorylation-mediated mechanisms involved in chromatic adaptation provides valuable insights into the intricate strategies employed by cyanobacteria to finely tune their photosynthetic efficiency in accordance with dynamic environmental stimuli [65]. The further exploration and elucidation of these intricate regulatory networks promises new insights into the underlying molecular mechanisms that control the adaptation and metabolic processes of cyanobacteria.

7. Protein Phosphorylation in Cyanobacterial Salt Stress Adaptation

Within the spectrum of cyanobacterial stress responses, salt stress emerges as a prominent context wherein protein phosphorylation assumes a pivotal role [68]. Recent studies have demonstrated rapid and significant changes in in vivo protein phosphorylation patterns within cultures of Synechocystis sp. PCC 6803 subjected to both hyper- and hypo-osmotic salt perturbations [69]. Noteworthy is the specificity of these effects to NaCl, as analogous alterations could not be induced by equimolar concentrations of glycerol. Furthermore, in vitro assays using extracts from salt-stressed cells or the addition of salt to extracts from unstressed cells have corroborated the observed modifications in the phosphorylation patterns [70,71]. However, comprehensive insights into the localization or identity of the phosphorylated species remain elusive. The response of Synechocystis sp. PCC 6803 to salt stress involves the modulation of energy transfer from phycobilisomes to PSI, reminiscent of a state transition phenomenon [2]. Furthermore, this adaptive process is associated with the augmentation of electron transport rates, implicating the involvement of both PSI and cytochrome oxidase activity. Despite the observed correlations, the detailed mechanistic role of protein phosphorylation in governing these physiological adjustments remains incompletely understood [72]. Although there exists compelling evidence implicating protein phosphorylation in the cyanobacterial response to salt stress, further investigations are necessary to elucidate the precise molecular mechanisms underlying these phenomena [73]. Such elucidation holds the potential to advance our comprehension of the stress adaptation mechanisms in cyanobacteria and may present promising avenues for biotechnological applications in the realm of stress-tolerant crop production or environmental remediation strategies [74].

8. Risk of Photo-Inhibition and Role of Inorganic Nutrients

Photo-inhibition poses a significant challenge to the viability of cyanobacteria, especially given their reliance on photoautotrophy, in which light serves as the primary energy source (Figure 3) [75]. This phenomenon occurs when the rate of absorption of light energy exceeds the cellular capacity to convert it into metabolic energy, leading to adverse consequences. A fundamental factor in alleviating photo-inhibition is the presence of essential inorganic nutrients, which act as cofactors in critical metabolic pathways [76].
CO2 is quantitatively the paramount inorganic nutrient for cyanobacteria, frequently becoming the limiting factor in environments harboring substantial cyanobacterial populations. In scenarios characterized by low CO2 concentrations, numerous cyanobacterial species initiate a bicarbonate-concentrating mechanism to bolster the efficiency of carbon fixation [77]. The term “carbon concentration mechanism” (CCM) is more accurate and comprehensive than “bicarbonate concentration mechanism” when referring to this process in cyanobacteria because it involves not only the concentration of bicarbonate but also the encapsulation of CO2 in carboxysomes. Carboxysomes are bacterial microcompartments that concentrate CO2 around the CO2-fixing enzyme Rubisco, enhancing carbon fixation while suppressing photorespiration. The carboxysome shell regulates the influx of bicarbonate and RuBP, while carbonic anhydrases within it convert bicarbonate to CO2, providing a high-CO2 microenvironment for Rubisco. Additionally, the intricate interaction between the CO2 availability and the phosphorylation of specific polypeptides implies a regulatory framework aimed at fine-tuning carbon assimilation in response to dynamic environmental cues [78].
Nitrogen, ranking as the second most pivotal inorganic nutrient for cyanobacteria, intricately orchestrates the cellular responses to environmental stimuli. The modulation of proteins engaged in nitrogen assimilation, exemplified by the GlnB protein, seems subject to phosphorylation-mediated regulation contingent upon variations in light quality and nitrogen availability [65]. This observation underscores the intricate interplay between photosynthetic electron transport and nitrogen metabolism, delineating a nuanced framework for cyanobacterial adaptation to environmental dynamics [79].
Phosphate, while quantitatively subordinate to nitrogen, frequently becomes a constraining factor in freshwater ecosystems [80]. Cyanobacteria manifest a nuanced reaction to phosphate scarcity akin to the extensively studied Pho regulon observed in enterobacteria [81]. This adaptive response involves the phosphorylation of response regulator proteins and facilitates the coordinated activation of phosphate uptake mechanisms, intending to increase the efficiency of cellular phosphate assimilation. While phosphorylation events are expected to play a role in the regulation of phosphate uptake and assimilation in cyanobacteria, the specific mechanisms are not accurately described in the search results provided. The results focus primarily on phosphate sensing, signaling, and adaptation mechanisms in plants, with some discussion of the role of protein phosphorylation in plant immunity and an E. coli study mentioning the phosphorylation of response regulators [82].
The convergence of the inorganic nutrient availability with cellular signaling cascades underscores the intricate regulatory mechanisms dictating cyanobacterial adaptation to dynamic environmental fluctuations [83]. A comprehensive exploration of the involvement of protein phosphorylation in orchestrating these adaptive responses offers potential avenues to unravel the molecular underpinnings of cyanobacterial adaptation and metabolic integration [84].

9. Integration of Light Harvesting and Nutrient Acquisition

Cyanobacteria, similar to higher plants, undergo oxygenic photosynthesis, a process characterized by the presence of two discrete photosystems embedded in the thylakoid membranes. These photosystems house intricate protein complexes, distinctively separate from the cytoplasmic membrane [85]. While chlorophyll a constitutes a critical element in the reaction centers of both photosystems, cyanobacteria deviate from higher plants by lacking the light-harvesting complex II (LHCII). Instead, they utilize phycobiliproteins, organized into macromolecular complexes known as phycobilisomes, as their primary light-harvesting apparatus [86]. The capacity of cyanobacteria to adjust to diverse light conditions involves reactions to fluctuations not solely in intensity but also in spectral characteristics. Protein phosphorylation has emerged as a pivotal factor in orchestrating these adaptive reactions, notably in response to alterations in spectral qualities [58]. Within the spectrum-driven adjustments exhibited by cyanobacteria, two principal phenomena stand out: state transitions and chromatic adaptation [87]. State transitions involve the dynamic redistribution of excitation energy between photosystem I (PSI) and photosystem II (PSII), thereby facilitating the optimization of the photosynthetic efficiency in response to specific lighting conditions [88]. Conversely, chromatic adaptation encompasses alterations in the composition of light-harvesting phycobiliproteins, which allow cyanobacteria to finely adjust their photosynthetic machinery according to the prevailing spectral qualities of light [89]. The clarification of these regulatory mechanisms highlights the complex interaction between protein phosphorylation and cyanobacterial photosynthetic adaptation strategies. Through the modulation of pivotal regulatory proteins implicated in state transitions and chromatic adaptation, protein phosphorylation substantially enhances the optimization of the photosynthetic efficacy in reaction to environmental stimuli [90]. Conclusively, the fusion of light harvesting and nutrient acquisition processes in cyanobacteria involves intricate molecular orchestrations governed by protein phosphorylation. Further investigation into these regulatory pathways would not only advance our comprehension of the cyanobacterial physiology but also present opportunities to harness their metabolic potential in biotechnological endeavors.

10. Protein Phosphorylation: A Key Player in Metabolic Integration

Protein phosphorylation serves as a critical regulatory mechanism orchestrating metabolic pathways within cyanobacteria. Recent findings underscore its essential role as a mediator in integrating various metabolic processes, significantly impacting cellular adaptation and survival strategies [91]. Playing a prominent role in metabolic regulation, protein phosphorylation dynamically adjusts enzyme activities, substrate flux, and cellular responses to environmental stimuli [92]. Cyanobacteria, being photoautotrophic, face the complex task of effectively utilizing light energy while maintaining a balance in nutrient acquisition for sustained growth [93]. This necessitates precise coordination between metabolic pathways and sensory perception mechanisms, where protein phosphorylation emerges as a pivotal component [94].
Recent investigations have broadened our understanding of protein phosphorylation in cyanobacterial metabolism, revealing its involvement in signal transduction cascades and regulatory networks governing nutrient sensing and utilization [47]. The integration of metabolic processes such as carbon fixation, nitrogen assimilation, and stress responses appears intricately linked to the phosphorylation statuses of key regulatory proteins [95]. Moreover, the identification of novel phosphorylation sites and regulatory motifs underscores the complexity and specificity of protein phosphorylation-mediated metabolic control [96]. State-of-the-art proteomic and phosphoproteomic analyses elucidate the dynamic interplay between phosphorylation events and metabolic fluxes, unveiling previously unexplored regulatory nodes and metabolic checkpoints [97]. The revelation of conserved phosphorylation-dependent signaling pathways highlights the evolutionary importance of protein phosphorylation as a conserved mechanism facilitating metabolic adaptation across diverse microbial taxa [98]. Furthermore, the elucidation of cyanobacteria-specific phosphorylation networks exposes unique adaptations tailored to their ecological niches, presenting promising targets for biotechnological applications and environmental engineering [99].
In synthesis, protein phosphorylation emerges as a central regulatory node in the intricate network of metabolic integration within cyanobacteria, orchestrating adaptive responses to varying environmental conditions and maintaining cellular homeostasis. Future endeavors aimed at deciphering the molecular mechanisms underlying protein phosphorylation-mediated metabolic regulation hold the potential to uncover new therapeutic avenues and deepen our comprehension of the microbial physiology in dynamic ecosystems.

11. Regulatory Role of Protein Kinases and Phosphatases in Cyanobacteria

Although the physiological roles of histidine protein kinases, particularly in phosphate acquisition, have received some attention, our understanding of the kinase and phosphatase machinery responsible for modulating the protein phosphorylation states in cyanobacteria remains somewhat limited [100]. Nevertheless, recent investigations have initiated a deeper exploration of the intricate regulatory mechanisms governing protein phosphorylation in these organisms, unveiling their pivotal significance in various cellular processes [92]. Studies conducted across diverse cyanobacterial species, including Synecbococczls sp. PCC 6301, Calothrix sp. PCC 7601, Anabaena sp. PCC 7120, and Synecbocystis sp. PCC 6803, have identified proteins prone to phosphorylation through monoester formation with hydroxyl-containing amino acids like serine, threonine, and tyrosine [65]. Noteworthy among these findings is the characterization of genes encoding proteins resembling eukaryotic serine/threonine protein kinases, as exemplified by the discovery of pknA in Anabaena sp. PCC 7120. This underscores the existence of a cyanobacterial kinase family intricately involved in signal transduction and regulatory processes [101,102].
Furthermore, the characterization of the ihpP gene in Nostoc commune UTEX 584, which encodes a polypeptide exhibiting both tyrosine and serine phosphatase activity, elucidates the intricate nature of protein phosphatases within cyanobacterial metabolism [103]. The detection of tyrosine-phosphorylated proteins in N. commune underscores the dynamic modulation of phosphorylation events in response to environmental stimuli [104].
Additionally, the activity of protein kinases and phosphatases in cyanobacteria is subject to modulation by metabolites and redox conditions, intricately linking cellular metabolism with phosphorylation-mediated signaling [105]. Evidently, the phosphorylation status of thylakoid proteins in Synechococcus sp. PCC 6301 is modulated by the redox state of plastoquinone, while protein phosphorylation in Anabaena sp. PCC 7120 is regulated by metabolites such as glucose 6-phosphate and ribulose 5-phosphate [106].
In brief, the intricate system involving protein kinases, phosphatases, and cellular metabolites orchestrates sophisticated signaling cascades in cyanobacteria, indispensable for their adept adaptation to dynamic environmental fluctuations and the maintenance of the metabolic equilibrium [107]. The enhanced comprehension of these regulatory mechanisms not only presents potential avenues for the discovery of innovative therapeutic targets but also facilitates advancements in our comprehension of the microbial physiology [108].

12. Future Directions and Implications

While the pivotal role of protein phosphorylation in various facets of cyanobacterial physiology, notably within two-component sensory systems, is firmly established, emerging evidence indicates its broader involvement in metabolic integration [58]. Cyanobacteria confront diverse challenges, not only navigating fluctuations in light intensity and quality but also managing dynamic shifts in metabolic demands and transitions between respiratory and photosynthetic pathways [109]. In response to fluctuating environmental conditions, cyanobacteria employ short-term adaptive strategies mediated by protein phosphorylation, which may precede longer-term transcriptional adaptations [110]. Significantly, changes in the relative proportions of photosystem I and II components within thylakoids, prompted by prolonged variations in light quality, serve as prime illustrations of these swift reactions. Thylakoids, conventionally recognized for their involvement in state transitions, are proposed to function as pivotal sites for metabolic integration facilitated by protein phosphorylation [111,112]. This conjecture implies that thylakoid-associated protein kinases possess the capacity to respond to an array of metabolic cues, encompassing the redox potential, energy status, and concentrations of critical metabolites [112]. Corroborative evidence is derived from investigations showcasing the redox-mediated modulation of protein phosphorylation in cyanobacterial cellular extracts and thylakoid systems that have been partially purified [113]. Additionally, the orchestration of protein phosphorylation by pivotal metabolites involved in both photosynthetic and respiratory pathways accentuates the intricate nature of metabolic integration [114]. In vivo examinations conducted on Synechocystis sp. PCC 6803 have unveiled shifts in protein phosphorylation patterns in response to diminished carbon availability, elicited by diverse environmental stimuli, with the predominant fraction of these proteins exhibiting membrane association [115].
The dynamic phosphorylation status of proteins, exemplified by GlnB’s responsiveness within nitrogen metabolism to variations in light’s spectral quality, highlights the intricate nature of metabolic integration in cyanobacteria [116]. Moving forward, it is imperative to delineate the cyanobacterial thylakoid-associated proteins and elucidate the regulatory roles of the kinases and phosphatases governing their phosphorylation dynamics [117]. This paradigm would not only enhance our understanding of the underlying regulatory mechanisms orchestrating cyanobacterial adaptation but also have considerable implications for biotechnological endeavors [118]. By harnessing the unique phosphorylation networks in cyanobacteria, there is potential to engineer strains with augmented stress resilience and develop targeted therapeutic interventions [119]. Consequently, further exploration into the involvement of protein phosphorylation in cyanobacterial metabolic integration represents a promising frontier for both fundamental research and practical applications in various scientific domains [93].

Author Contributions

S.F. and R.Z.: conceptualization, data curation, writing—original draft; T.N.: formal analysis, investigation, methodology, resources; R.Z.: supervision, validation, visualization, writing—review and editing; S.F.: writing—review and editing. All authors have read and agreed to the published version of the manuscript.

Funding

The authors would like to extend their sincere appreciation to the USDA Hatch Project SD00H691-20 titled Engineering Solar-Powered N2-Fixing Cyanobacteria for Agricultural and Industrial Applications (to R.Z.).

Institutional Review Board Statement

Not applicable. This manuscript is a review article that does not report on or involve any animals, humans, human data, human tissue, or plants.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Nawaz, T.; Gu, L.; Fahad, S.; Saud, S.; Harrison, M.T.; Zhou, R. Sustainable protein production through genetic engineering of cyanobacteria and use of atmospheric N2 gas. Food Energy Secur. 2024, 13, e536. [Google Scholar] [CrossRef]
  2. Ditty, J.; Williams, S.; Golden, S. A cyanobacterial circadian timing mechanism. Annu. Rev. Genet. 2003, 37, 513–543. [Google Scholar] [CrossRef]
  3. Johnson, L.N. The regulation of protein phosphorylation. Biochem. Soc. Trans. 2009, 37, 627–641. [Google Scholar] [CrossRef]
  4. Babele, P.K.; Kumar, J.; Chaturvedi, V. Proteomic de-regulation in cyanobacteria in response to abiotic stresses. Front. Microbiol. 2019, 10, 429649. [Google Scholar] [CrossRef]
  5. Steuer, R.; Knoop, H.; Machné, R. Modelling cyanobacteria: From metabolism to integrative models of phototrophic growth. J. Exp. Bot. 2012, 63, 2259–2274. [Google Scholar] [CrossRef]
  6. Maberly, S.C. The fitness of the environments of air and water for photosynthesis, growth, reproduction and dispersal of photoautotrophs: An evolutionary and biogeochemical perspective. Aquat. Bot. 2014, 118, 4–13. [Google Scholar] [CrossRef]
  7. Samiotis, G. Wastewater Treatment and Valorization Coupled with Cyanobacterium Synechococcus Elongatus PCC 7942 Cultivation. Ph.D. Thesis, University of Western Macedonia, Kozani, Greece, 2022. [Google Scholar]
  8. Wu, X.; Xu, M.; Geng, M.; Chen, S.; Little, P.J.; Xu, S.; Weng, J. Targeting protein modifications in metabolic diseases: Molecular mechanisms and targeted therapies. Signal Transduct. Target. Ther. 2023, 8, 220. [Google Scholar] [CrossRef]
  9. Capra, E.J.; Laub, M.T. Evolution of two-component signal transduction systems. Annu. Rev. Microbiol. 2012, 66, 325–347. [Google Scholar] [CrossRef]
  10. Wolanin, P.M.; Thomason, P.A.; Stock, J.B. Histidine protein kinases: Key signal transducers outside the animal kingdom. Genome Biol. 2002, 3, 1–8. [Google Scholar] [CrossRef]
  11. Jurdzinski, K.T.; Mehrshad, M.; Delgado, L.F.; Deng, Z.; Bertilsson, S.; Andersson, A.F. Large-scale phylogenomics of aquatic bacteria reveal molecular mechanisms for adaptation to salinity. Sci. Adv. 2023, 9, eadg2059. [Google Scholar] [CrossRef]
  12. Ardito, F.; Giuliani, M.; Perrone, D.; Troiano, G.; Lo Muzio, L. The crucial role of protein phosphorylation in cell signaling and its use as targeted therapy. Int. J. Mol. Med. 2017, 40, 271–280. [Google Scholar] [CrossRef]
  13. Çelekli, A.; Zariç, Ö.E. Plasma-Enhanced Microalgal Cultivation: A Sustainable Approach for Biofuel and Biomass Production. In Emerging Applications of Plasma Science in Allied Technologies; IGI Global: Hershey, PA, USA, 2024; pp. 243–263. [Google Scholar]
  14. Nawaz, T.; Gu, L.; Fahad, S.; Saud, S.; Bleakley, B.; Zhou, R. Exploring Sustainable Agriculture with Nitrogen-Fixing Cyanobacteria and Nanotechnology. Molecules 2024, 29, 2534. [Google Scholar] [CrossRef]
  15. Liu, J.; Qian, C.; Cao, X. Post-translational modification control of innate immunity. Immunity 2016, 45, 15–30. [Google Scholar] [CrossRef]
  16. Cohen, S.E.; Golden, S.S. Circadian rhythms in cyanobacteria. Microbiol. Mol. Biol. Rev. 2015, 79, 373–385. [Google Scholar] [CrossRef]
  17. Cembella, A.D.; Antia, N.J.; Harrison, P.J. The utilization of inorganic and organic phosphorous compounds as nutrients by eukaryotic microalgae: A multidisciplinary perspective: Part I. CRC Crit. Rev. Microbiol. 1982, 10, 317–391. [Google Scholar] [CrossRef] [PubMed]
  18. Kolodiazhnyi, O.I. Phosphorus compounds of natural origin: Prebiotic, stereochemistry, application. Symmetry 2021, 13, 889. [Google Scholar] [CrossRef]
  19. Iyer, L.M.; Anantharaman, V.; Krishnan, A.; Burroughs, A.M.; Aravind, L. Jumbo phages: A comparative genomic overview of core functions and adaptions for biological conflicts. Viruses 2021, 13, 63. [Google Scholar] [CrossRef] [PubMed]
  20. Stierum, R.H.; Dianov, G.L.; Bohr, V.A. Single-nucleotide patch base excision repair of uracil in DNA by mitochondrial protein extracts. Nucleic Acids Res. 1999, 27, 3712–3719. [Google Scholar] [CrossRef] [PubMed]
  21. Borkovich, K.A.; Alex, L.A.; Yarden, O.; Freitag, M.; Turner, G.E.; Read, N.D.; Seiler, S.; Bell-Pedersen, D.; Paietta, J.; Plesofsky, N.; et al. Lessons from the genome sequence of Neurospora crassa: Tracing the path from genomic blueprint to multicellular organism. Microbiol. Mol. Biol. Rev. 2004, 68, 1–108. [Google Scholar] [CrossRef] [PubMed]
  22. Yang, M.-K.; Qiao, Z.-X.; Zhang, W.-Y.; Xiong, Q.; Zhang, J.; Li, T.; Ge, F.; Zhao, J.-D. Global phosphoproteomic analysis reveals diverse functions of serine/threonine/tyrosine phosphorylation in the model cyanobacterium Synechococcus sp. strain PCC 7002. J. Proteome Res. 2013, 12, 1909–1923. [Google Scholar] [CrossRef]
  23. Dumas, L.; Zito, F.; Blangy, S.; Auroy, P.; Johnson, X.; Peltier, G.; Alric, J. A stromal region of cytochrome b 6 f subunit IV is involved in the activation of the Stt7 kinase in Chlamydomonas. Proc. Natl. Acad. Sci. USA 2017, 114, 12063–12068. [Google Scholar] [CrossRef]
  24. Carlberg, I.; Hansson, M.; Kieselbach, T.; Schröder, W.P.; Andersson, B.; Vener, A.V. A novel plant protein undergoing light-induced phosphorylation and release from the photosynthetic thylakoid membranes. Proc. Natl. Acad. Sci. USA 2003, 100, 757–762. [Google Scholar] [CrossRef] [PubMed]
  25. Srivastava, R.; Singh, N.; Kanda, T.; Yadav, S.; Yadav, S.; Atri, N. Cyanobacterial Proteomics: Diversity and Dynamics. J. Proteome Res. 2024. [Google Scholar] [CrossRef] [PubMed]
  26. Mukherjee, S.; Hao, Y.-H.; Orth, K. A newly discovered post-translational modification–the acetylation of serine and threonine residues. Trends Biochem. Sci. 2007, 32, 210–216. [Google Scholar] [CrossRef] [PubMed]
  27. Seok, S.-H. Structural insights into protein regulation by phosphorylation and substrate recognition of protein kinases/phosphatases. Life 2021, 11, 957. [Google Scholar] [CrossRef] [PubMed]
  28. Li, H.; Yang, Y.; Hong, W.; Huang, M.; Wu, M.; Zhao, X. Applications of genome editing technology in the targeted therapy of human diseases: Mechanisms, advances and prospects. Signal Transduct. Target. Ther. 2020, 5, 1. [Google Scholar] [CrossRef] [PubMed]
  29. Appleby, J.L. The Activation Mechanism of Response Regulator Chey; The University of North Carolina at Chapel Hill: Chapel Hill, NC, USA, 1997. [Google Scholar]
  30. Marijuán, P.C.; Navarro, J. From molecular recognition to the “vehicles” of evolutionary complexity: An informational approach. Int. J. Mol. Sci. 2021, 22, 11965. [Google Scholar] [CrossRef] [PubMed]
  31. Getz, L.J.; Runte, C.S.; Rainey, J.K.; Thomas, N.A. Tyrosine phosphorylation as a widespread regulatory mechanism in prokaryotes. J. Bacteriol. 2019, 201, 10–1128. [Google Scholar] [CrossRef] [PubMed]
  32. Boehi, F.; Manetsch, P.; Hottiger, M.O. Interplay between ADP-ribosyltransferases and essential cell signaling pathways controls cellular responses. Cell Discov. 2021, 7, 104. [Google Scholar] [CrossRef]
  33. Falke, J.J.; Bass, R.B.; Butler, S.L.; Chervitz, S.A.; Danielson, M.A. The two-component signaling pathway of bacterial chemotaxis: A molecular view of signal transduction by receptors, kinases, and adaptation enzymes. Annu. Rev. Cell Dev. Biol. 1997, 13, 457–512. [Google Scholar] [CrossRef]
  34. Buschiazzo, A.; Trajtenberg, F. Two-component sensing and regulation: How do histidine kinases talk with response regulators at the molecular level? Annu. Rev. Microbiol. 2019, 73, 507–528. [Google Scholar] [CrossRef] [PubMed]
  35. Bissett, A.; Brown, M.V.; Siciliano, S.D.; Thrall, P.H. Microbial community responses to anthropogenically induced environmental change: Towards a systems approach. Ecol. Lett. 2013, 16, 128–139. [Google Scholar] [CrossRef] [PubMed]
  36. Mascher, T.; Helmann, J.D.; Unden, G. Stimulus perception in bacterial signal-transducing histidine kinases. Microbiol. Mol. Biol. Rev. 2006, 70, 910–938. [Google Scholar] [CrossRef] [PubMed]
  37. Tang, K.; Beyer, H.M.; Zurbriggen, M.D.; Gärtner, W. The red edge: Bilin-binding photoreceptors as optogenetic tools and fluorescence reporters. Chem. Rev. 2021, 121, 14906–14956. [Google Scholar] [CrossRef] [PubMed]
  38. Schluchter, W.M. The Characterization of Photosystem I and Ferredoxin-NADP (+) Oxidoreductase in the Cyanobacterium Synechococcus sp. PCC 7002; The Pennsylvania State University: University Park, PA, USA, 1994. [Google Scholar]
  39. Koskinen, S.; Kurkela, J.; Linhartová, M.; Tyystjärvi, T. The genome sequence of Synechocystis sp. PCC 6803 substrain GT-T and its implications for the evolution of PCC 6803 substrains. FEBS Open Bio 2023, 13, 701–712. [Google Scholar] [CrossRef] [PubMed]
  40. Vakonakis, I.; Klewer, D.A.; Williams, S.B.; Golden, S.S.; LiWang, A.C. Structure of the N-terminal domain of the circadian clock-associated histidine kinase SasA. J. Mol. Biol. 2004, 342, 9–17. [Google Scholar] [CrossRef] [PubMed]
  41. Horstmann, N.; Tran, C.N.; Brumlow, C.; DebRoy, S.; Yao, H.; Gonzalez, G.N.; Makthal, N.; Kumaraswami, M.; Shelburne, S.A. Phosphatase activity of the control of virulence sensor kinase CovS is critical for the pathogenesis of group A streptococcus. PLoS Pathog. 2018, 14, e1007354. [Google Scholar] [CrossRef] [PubMed]
  42. Deussing, J.M. Targeted mutagenesis tools for modelling psychiatric disorders. Cell Tissue Res. 2013, 354, 9–25. [Google Scholar] [CrossRef]
  43. May, J.P. Characterisation of the slr1212 Genomic Region of the Freshwater Cyanobacterium Synechocystis sp. PCC 6803; University of Warwick: Coventry, UK, 2001. [Google Scholar]
  44. Lezhneva, L. Identification of Novel Nuclear Factors Required for Chloroplast Gene Expression and Photosystem I Assembly. Ph.D. Thesis, LMU, Munich, Germany, 2005. [Google Scholar]
  45. Samuels, D.S.; Lybecker, M.C.; Yang, X.F.; Ouyang, Z.; Bourret, T.J.; Boyle, W.K.; Stevenson, B.; Drecktrah, D.; Caimano, M.J. Gene regulation and transcriptomics. Curr. Issues Mol. Biol. 2021, 42, 223–266. [Google Scholar]
  46. Laub, M.T. The Role of Two-Component Signal Transduction Systems in Bacterial Stress Responses. In Bacterial Stress Responses; John Wiley & Sons: Hoboken, NJ, USA, 2010; pp. 45–58. [Google Scholar]
  47. Rachedi, R.; Foglino, M.; Latifi, A. Stress signaling in cyanobacteria: A mechanistic overview. Life 2020, 10, 312. [Google Scholar] [CrossRef]
  48. Nawaz, T.; Saud, S.; Gu, L.; Khan, I.; Fahad, S.; Zhou, R. Cyanobacteria: Harnessing the Power of Microorganisms for Plant Growth Promotion, Stress Alleviation, and Phytoremediation in the Era of Sustainable Agriculture. Plant Stress 2024, 11, 100399. [Google Scholar] [CrossRef]
  49. Ringsmuth, A.K.; Landsberg, M.J.; Hankamer, B. Can photosynthesis enable a global transition from fossil fuels to solar fuels, to mitigate climate change and fuel-supply limitations? Renew. Sustain. Energy Rev. 2016, 62, 134–163. [Google Scholar] [CrossRef]
  50. Stitt, M.; Sulpice, R.; Keurentjes, J. Metabolic networks: How to identify key components in the regulation of metabolism and growth. Plant Physiol. 2010, 152, 428–444. [Google Scholar] [CrossRef] [PubMed]
  51. Meloni, M.; Gurrieri, L.; Fermani, S.; Velie, L.; Sparla, F.; Crozet, P.; Henri, J.; Zaffagnini, M. Ribulose-1, 5-bisphosphate regeneration in the Calvin-Benson-Bassham cycle: Focus on the last three enzymatic steps that allow the formation of Rubisco substrate. Front. Plant Sci. 2023, 14, 1130430. [Google Scholar] [CrossRef] [PubMed]
  52. Khan, F.; Siddique, A.B.; Shabala, S.; Zhou, M.; Zhao, C. Phosphorus plays key roles in regulating plants’ physiological responses to abiotic stresses. Plants 2023, 12, 2861. [Google Scholar] [CrossRef] [PubMed]
  53. Burnap, R.L. Systems and photosystems: Cellular limits of autotrophic productivity in cyanobacteria. Front. Bioeng. Biotechnol. 2015, 3, 1. [Google Scholar] [CrossRef] [PubMed]
  54. Cray, J.A.; Bell, A.N.; Bhaganna, P.; Mswaka, A.Y.; Timson, D.J.; Hallsworth, J.E. The biology of habitat dominance; can microbes behave as weeds? Microb. Biotechnol. 2013, 6, 453–492. [Google Scholar] [CrossRef] [PubMed]
  55. Rakesh, R.; PriyaDharshini, L.C.; Sakthivel, K.M.; Rasmi, R.R. Role and regulation of autophagy in cancer. Biochim. Et Biophys. Acta (BBA)-Mol. Basis Dis. 2022, 1868, 166400. [Google Scholar] [CrossRef] [PubMed]
  56. Chen, M.-Y.; Teng, W.-K.; Zhao, L.; Hu, C.-X.; Zhou, Y.-K.; Han, B.-P.; Song, L.-R.; Shu, W.-S. Comparative genomics reveals insights into cyanobacterial evolution and habitat adaptation. ISME J. 2021, 15, 211–227. [Google Scholar] [CrossRef]
  57. Hawkins, R.D.; Hon, G.C.; Ren, B. Next-generation genomics: An integrative approach. Nat. Rev. Genet. 2010, 11, 476–486. [Google Scholar] [CrossRef]
  58. Wiltbank, L.B.; Kehoe, D.M. Diverse light responses of cyanobacteria mediated by phytochrome superfamily photoreceptors. Nat. Rev. Microbiol. 2019, 17, 37–50. [Google Scholar] [CrossRef] [PubMed]
  59. Larkum, A.W. Light-harvesting in cyanobacteria and eukaryotic algae: An overview. In Photosynthesis in Algae: Biochemical and Physiological Mechanisms; Springer: Cham, Switzerland, 2020; pp. 207–260. [Google Scholar]
  60. Kehoe, D.M.; Grossman, A.R. Complementary chromatic adaptation: Photoperception to gene regulation. In Seminars in Cell Biology; Elsevier: Amsterdam, The Netherlands, 1994. [Google Scholar]
  61. de Marsac, N.T. Differentiation of hormogonia and relationships with other biological processes. In The Molecular Biology of Cyanobacteria; Springer: Berlin/Heidelberg, Germany, 1994; pp. 825–842. [Google Scholar]
  62. Cohen, P. The origins of protein phosphorylation. Nat. Cell Biol. 2002, 4, E127–E130. [Google Scholar] [CrossRef] [PubMed]
  63. Buljan, M.; Ciuffa, R.; van Drogen, A.; Vichalkovski, A.; Mehnert, M.; Rosenberger, G.; Lee, S.; Varjosalo, M.; Pernas, L.E.; Spegg, V.; et al. Kinase interaction network expands functional and disease roles of human kinases. Mol. Cell 2020, 79, 504–520.e9. [Google Scholar] [CrossRef] [PubMed]
  64. Valente-Paterno, M. Spatial and Temporal Patterns of Localized Thylakoid Biogenesis in the Chloroplast of Chlamydomonas reinhardtii; Concordia University: Montreal, QC, Canada, 2018. [Google Scholar]
  65. Mann, N.H. Protein phosphorylation in cyanobacteria. Microbiology 1994, 140, 3207–3215. [Google Scholar] [CrossRef] [PubMed]
  66. Salomon, A.R.; Ficarro, S.B.; Brill, L.M.; Brinker, A.; Phung, Q.T.; Ericson, C.; Sauer, K.; Brock, A.; Horn, D.M.; Schultz, P.G.; et al. Profiling of tyrosine phosphorylation pathways in human cells using mass spectrometry. Proc. Natl. Acad. Sci. USA 2003, 100, 443–448. [Google Scholar] [CrossRef] [PubMed]
  67. Chen, Z.; Zhan, J.; Chen, Y.; Yang, M.; He, C.; Ge, F.; Wang, Q. Effects of phosphorylation of β subunits of phycocyanins on state transition in the model cyanobacterium Synechocystis sp. PCC 6803. Plant Cell Physiol. 2015, 56, 1997–2013. [Google Scholar] [CrossRef]
  68. Teoh, F.K.Y. Membrane Proteins and Protein-Protein Interactions in Marine Cyanobacteria; Macquarie University: Sydney, Australia, 2022. [Google Scholar]
  69. Li, S.; Dean, S.; Li, Z.; Horecka, J.; Deschenes, R.J.; Fassler, J.S. The eukaryotic two-component histidine kinase Sln1p regulates OCH1 via the transcription factor, Skn7p. Mol. Biol. Cell 2002, 13, 412–424. [Google Scholar] [CrossRef] [PubMed]
  70. Baxter, R.; Gibbons, N. The glycerol dehydrogenases of Pseudomonas salinaria, Vibrio costicolus, and Escherichia coli in relation to bacterial halophilism. Can. J. Biochem. Physiol. 1954, 32, 206–217. [Google Scholar] [CrossRef]
  71. Batelli, G.; Verslues, P.E.; Agius, F.; Qiu, Q.; Fujii, H.; Pan, S.; Schumaker, K.S.; Grillo, S.; Zhu, J.-K. SOS2 promotes salt tolerance in part by interacting with the vacuolar H+-ATPase and upregulating its transport activity. Mol. Cell. Biol. 2007, 27, 7781–7790. [Google Scholar] [CrossRef]
  72. Eberhard, S.; Finazzi, G.; Wollman, F.-A. The dynamics of photosynthesis. Annu. Rev. Genet. 2008, 42, 463–515. [Google Scholar] [CrossRef]
  73. Muhseen, Z.T.; Xiong, Q.; Chen, Z.; Ge, F. Proteomics studies on stress responses in diatoms. Proteomics 2015, 15, 3943–3953. [Google Scholar] [CrossRef] [PubMed]
  74. Atakkatan, A.; Innesent, S.; Prajapat, S.P.; Pandit, S.; Khanna, N. Potential of Extremophilic Algae for the Synthesis of Value-Added Products, in Extremophiles; CRC Press: Boca Raton, FL, USA, 2023; pp. 80–114. [Google Scholar]
  75. Zarekarizi, A.; Hoffmann, L.; Burritt, D.J. The potential of manipulating light for the commercial production of carotenoids from algae. Algal Res. 2023, 71, 103047. [Google Scholar] [CrossRef]
  76. Perez-Garcia, O.; Escalante, F.M.E.; De-Bashan, L.E.; Bashan, Y. Heterotrophic cultures of microalgae: Metabolism and potential products. Water Res. 2011, 45, 11–36. [Google Scholar] [CrossRef] [PubMed]
  77. Price, G.D.; Badger, M.R.; Woodger, F.J.; Long, B.M. Advances in understanding the cyanobacterial CO2-concentrating-mechanism (CCM): Functional components, Ci transporters, diversity, genetic regulation and prospects for engineering into plants. J. Exp. Bot. 2008, 59, 1441–1461. [Google Scholar] [CrossRef] [PubMed]
  78. Balparda, M.; Bouzid, M.; Martinez, M.d.P.; Zheng, K.; Schwarzländer, M.; Maurino, V.G. Regulation of plant carbon assimilation metabolism by post-translational modifications. Plant J. 2023, 114, 1059–1079. [Google Scholar] [CrossRef] [PubMed]
  79. Freeman, C.J.; Easson, C.G.; Fiore, C.L.; Thacker, R.W. Sponge–microbe interactions on coral reefs: Multiple evolutionary solutions to a complex environment. Front. Mar. Sci. 2021, 8, 705053. [Google Scholar] [CrossRef]
  80. Lindsay, E.A.; Colloff, M.J.; Gibb, N.L.; Wakelin, S.A. The abundance of microbial functional genes in grassy woodlands is influenced more by soil nutrient enrichment than by recent weed invasion or livestock exclusion. Appl. Environ. Microbiol. 2010, 76, 5547–5555. [Google Scholar] [CrossRef] [PubMed]
  81. Carini, P.J. Genome-Enabled Investigation of the Minimal Growth Requirements Andphosphate Metabolism for Pelagibacter Marine bacteria. Ph.D. Thesis, Oregon State University, Corvallis, OR, USA, 2013. [Google Scholar]
  82. Zhang, Z.; Liao, H.; Lucas, W.J. Molecular mechanisms underlying phosphate sensing, signaling, and adaptation in plants. J. Integr. Plant Biol. 2014, 56, 192–220. [Google Scholar] [CrossRef] [PubMed]
  83. Flores-Cotera, L.B.; Chávez-Cabrera, C.; Martínez-Cárdenas, A.; Sánchez, S.; García-Flores, O.U. Deciphering the mechanism by which the yeast Phaffia rhodozyma responds adaptively to environmental, nutritional, and genetic cues. J. Ind. Microbiol. Biotechnol. 2021, 48, kuab048. [Google Scholar] [CrossRef]
  84. Trevisan, R.; Mello, D.F. Redox control of antioxidants, metabolism, immunity, and development at the core of stress adaptation of the oyster Crassostrea gigas to the dynamic intertidal environment. In Free Radical Biology and Medicine; Elsevier: Amsterdam, The Netherlands, 2023. [Google Scholar]
  85. Battchikova, N.; Angeleri, M.; Aro, E.-M. Proteomic approaches in research of cyanobacterial photosynthesis. Photosynth. Res. 2015, 126, 47–70. [Google Scholar] [CrossRef]
  86. Kirilovsky, D.; Kaňa, R.; Prášil, O. Mechanisms modulating energy arriving at reaction centers in cyanobacteria. In Non-Photochemical Quenching and Energy Dissipation in Plants, Algae and Cyanobacteria; Springer: Berlin/Heidelberg, Germany, 2014; pp. 471–501. [Google Scholar]
  87. Calderon, R.H. More than just a pair of blue genes: How cyanobacteria adapt to changes in their light environment. Physiol. Plant. 2020, 170, 7–9. [Google Scholar] [CrossRef] [PubMed]
  88. Derks, A.; Schaven, K.; Bruce, D. Diverse mechanisms for photoprotection in photosynthesis. Dynamic regulation of photosystem II excitation in response to rapid environmental change. Biochim. Et Biophys. Acta (BBA)-Bioenerg. 2015, 1847, 468–485. [Google Scholar] [CrossRef] [PubMed]
  89. Chen, M.; Hernandez-Prieto, M.A.; Loughlin, P.C.; Li, Y.; Willows, R.D. Genome and proteome of the chlorophyll f-producing cyanobacterium Halomicronema hongdechloris: Adaptative proteomic shifts under different light conditions. BMC Genom. 2019, 20, 207. [Google Scholar] [CrossRef] [PubMed]
  90. Zhang, W.J.; Zhou, Y.; Zhang, Y.; Su, Y.H.; Xu, T. Protein phosphorylation: A molecular switch in plant signaling. Cell Rep. 2023, 42, 112729. [Google Scholar] [CrossRef] [PubMed]
  91. Sakr, S.; Wang, M.; Dédaldéchamp, F.; Perez-Garcia, M.-D.; Ogé, L.; Hamama, L.; Atanassova, R. The sugar-signaling hub: Overview of regulators and interaction with the hormonal and metabolic network. Int. J. Mol. Sci. 2018, 19, 2506. [Google Scholar] [CrossRef] [PubMed]
  92. Humphrey, S.J.; James, D.E.; Mann, M. Protein phosphorylation: A major switch mechanism for metabolic regulation. Trends Endocrinol. Metab. 2015, 26, 676–687. [Google Scholar] [CrossRef] [PubMed]
  93. Berla, B.M.; Saha, R.; Immethun, C.M.; Maranas, C.D.; Moon, T.S.; Pakrasi, H.B. Synthetic biology of cyanobacteria: Unique challenges and opportunities. Front. Microbiol. 2013, 4, 59403. [Google Scholar] [CrossRef] [PubMed]
  94. Chubukov, V.; Gerosa, L.; Kochanowski, K.; Sauer, U. Coordination of microbial metabolism. Nat. Rev. Microbiol. 2014, 12, 327–340. [Google Scholar] [CrossRef] [PubMed]
  95. Alves, H.L.; Matiolli, C.C.; Soares, R.C.; Almadanim, M.C.; Oliveira, M.M.; Abreu, I.A. Carbon/nitrogen metabolism and stress response networks–calcium-dependent protein kinases as the missing link? J. Exp. Bot. 2021, 72, 4190–4201. [Google Scholar] [CrossRef]
  96. Lasonder, E.; Green, J.L.; Camarda, G.; Talabani, H.; Holder, A.A.; Langsley, G.; Alano, P. The Plasmodium falciparum schizont phosphoproteome reveals extensive phosphatidylinositol and cAMP-protein kinase A signaling. J. Proteome Res. 2012, 11, 5323–5337. [Google Scholar] [CrossRef]
  97. Vaga, S.; Bernardo-Faura, M.; Cokelaer, T.; Maiolica, A.; Barnes, C.A.; Gillet, L.C.; Hegemann, B.; van Drogen, F.; Sharifian, H.; Klipp, E.; et al. Phosphoproteomic analyses reveal novel cross-modulation mechanisms between two signaling pathways in yeast. Mol. Syst. Biol. 2014, 10, 767. [Google Scholar] [CrossRef] [PubMed]
  98. Mast, F.D.; Ratushny, A.V.; Aitchison, J.D. Systems cell biology. J. Cell Biol. 2014, 206, 695–706. [Google Scholar] [CrossRef] [PubMed]
  99. Schmelling, N.M.; Scheurer, N.; Köbler, C.; Wilde, A.; Axmann, I.M. Diversity of timing systems in cyanobacteria and beyond. In Circadian Rhythms in Bacteria and Microbiomes; Springer: Berlin/Heidelberg, Germany, 2021; pp. 179–202. [Google Scholar]
  100. Grangeasse, C.; Nessler, S.; Mijakovic, I. Bacterial tyrosine kinases: Evolution, biological function and structural insights. Philos. Trans. R. Soc. B Biol. Sci. 2012, 367, 2640–2655. [Google Scholar] [CrossRef] [PubMed]
  101. Av-Gay, Y.; Jamil, S.; Drews, S.J. Expression and characterization of the Mycobacterium tuberculosis serine/threonine protein kinase PknB. Infect. Immun. 1999, 67, 5676–5682. [Google Scholar] [CrossRef] [PubMed]
  102. Biswas, K.H.; Shenoy, A.R.; Dutta, A.; Visweswariah, S.S. The evolution of guanylyl cyclases as multidomain proteins: Conserved features of kinase-cyclase domain fusions. J. Mol. Evol. 2009, 68, 587–602. [Google Scholar] [CrossRef]
  103. Xie, W.Q.; Whitton, B.A.; Simon, J.W.; Jäger, K.; Reed, D.; Potts, M. Nostoc commune UTEX 584 gene expressing indole phosphate hydrolase activity in Escherichia coli. J. Bacteriol. 1989, 171, 708–713. [Google Scholar] [CrossRef] [PubMed]
  104. Lundby, A.; Secher, A.; Lage, K.; Nordsborg, N.B.; Dmytriyev, A.; Lundby, C.; Olsen, J.V. Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues. Nat. Commun. 2012, 3, 876. [Google Scholar] [CrossRef] [PubMed]
  105. Khan, M.Z.; Kaur, P.; Nandicoori, V.K. Targeting the messengers: Serine/threonine protein kinases as potential targets for antimycobacterial drug development. IUBMB Life 2018, 70, 889–904. [Google Scholar] [CrossRef] [PubMed]
  106. Veaudor, T.; Blanc-Garin, V.; Chenebault, C.; Diaz-Santos, E.; Sassi, J.-F.; Cassier-Chauvat, C.; Chauvat, F. Recent advances in the photoautotrophic metabolism of cyanobacteria: Biotechnological implications. Life 2020, 10, 71. [Google Scholar] [CrossRef]
  107. Qin, S.; Kitty, I.; Hao, Y.; Zhao, F.; Kim, W. Maintaining genome integrity: Protein kinases and phosphatases orchestrate the balancing act of DNA double-strand breaks repair in cancer. Int. J. Mol. Sci. 2023, 24, 10212. [Google Scholar] [CrossRef]
  108. Koo, H.; Allan, R.N.; Howlin, R.P.; Stoodley, P.; Hall-Stoodley, L. Targeting microbial biofilms: Current and prospective therapeutic strategies. Nat. Rev. Microbiol. 2017, 15, 740–755. [Google Scholar] [CrossRef] [PubMed]
  109. Aryal, U.K.; Stöckel, J.; Krovvidi, R.K.; Gritsenko, M.A.; Monroe, M.E.; Moore, R.J.; Koppenaal, D.W.; Smith, R.D.; Pakrasi, H.B.; Jacobs, J.M. Dynamic proteomic profiling of a unicellular cyanobacterium Cyanothece ATCC51142 across light-dark diurnal cycles. BMC Syst. Biol. 2011, 5, 194. [Google Scholar] [CrossRef] [PubMed]
  110. Moxon, R.; Bayliss, C.; Hood, D. Bacterial contingency loci: The role of simple sequence DNA repeats in bacterial adaptation. Annu. Rev. Genet. 2006, 40, 307–333. [Google Scholar] [CrossRef] [PubMed]
  111. Puthiyaveetil, S.; Tsabari, O.; Lowry, T.; Lenhert, S.; Lewis, R.R.; Reich, Z.; Kirchhoff, H. Compartmentalization of the protein repair machinery in photosynthetic membranes. Proc. Natl. Acad. Sci. USA 2014, 111, 15839–15844. [Google Scholar] [CrossRef]
  112. Longoni, F.P.; Goldschmidt-Clermont, M. Thylakoid protein phosphorylation in chloroplasts. Plant Cell Physiol. 2021, 62, 1094–1107. [Google Scholar] [CrossRef] [PubMed]
  113. Aro, E.-M.; Ohad, I. Redox regulation of thylakoid protein phosphorylation. Antioxid. Redox Signal. 2003, 5, 55–67. [Google Scholar] [CrossRef] [PubMed]
  114. Gibon, Y.; Usadel, B.; Blaesing, O.E.; Kamlage, B.; Hoehne, M.; Trethewey, R.; Stitt, M. Integration of metabolite with transcript and enzyme activity profiling during diurnal cycles in Arabidopsis rosettes. Genome Biol. 2006, 7, R76. [Google Scholar] [CrossRef] [PubMed]
  115. Zhang, C.C.; Jang, J.; Sakr, S.; Wang, L. Protein phosphorylation on Ser, Thr and Tyr residues in cyanobacteria. J. Mol. Microbiol. Biotechnol. 2005, 9, 154–166. [Google Scholar] [CrossRef]
  116. Whitford, D.S. Function of the Synechocystis RNA Helicase, CrhR, and Its Cyanobacterial Homologs. Ph.D. Thesis, University of Alberta, Edmonton, AB, Canada, 2020. [Google Scholar]
  117. Wittkopp, T.M.; Saroussi, S.; Yang, W.; Grossman, A.R.; Kirchhoff, H. The GreenCut: Functions and relationships of proteins conserved in green lineage organisms. In Chloroplasts: Current Research and Future Trends; Institute of Biological Chemistry, Washington State University: Pullman, WA, USA, 2016; pp. 241–278. [Google Scholar]
  118. Ferrari, R.C.; Freschi, L. C4/CAM facultative photosynthesis as a means to improve plant sustainable productivity under abiotic-stressed conditions: Regulatory mechanisms and biotechnological implications. In Plant Signaling Molecules; Elsevier: Amsterdam, The Netherlands, 2019; pp. 517–532. [Google Scholar]
  119. Satta, A.; Esquirol, L.; Ebert, B.E. Current metabolic engineering strategies for photosynthetic bioproduction in cyanobacteria. Microorganisms 2023, 11, 455. [Google Scholar] [CrossRef]
Figure 1. Indications of protein phosphorylation: forms and functions.
Figure 1. Indications of protein phosphorylation: forms and functions.
Kinasesphosphatases 02 00013 g001
Figure 2. Historical perspective: early studies on protein phosphorylation in prokaryotes.
Figure 2. Historical perspective: early studies on protein phosphorylation in prokaryotes.
Kinasesphosphatases 02 00013 g002
Figure 3. Risk of photo-inhibition and role of inorganic nutrients.
Figure 3. Risk of photo-inhibition and role of inorganic nutrients.
Kinasesphosphatases 02 00013 g003
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Nawaz, T.; Fahad, S.; Zhou, R. Protein Phosphorylation Nexus of Cyanobacterial Adaptation and Metabolism. Kinases Phosphatases 2024, 2, 209-223. https://doi.org/10.3390/kinasesphosphatases2020013

AMA Style

Nawaz T, Fahad S, Zhou R. Protein Phosphorylation Nexus of Cyanobacterial Adaptation and Metabolism. Kinases and Phosphatases. 2024; 2(2):209-223. https://doi.org/10.3390/kinasesphosphatases2020013

Chicago/Turabian Style

Nawaz, Taufiq, Shah Fahad, and Ruanbao Zhou. 2024. "Protein Phosphorylation Nexus of Cyanobacterial Adaptation and Metabolism" Kinases and Phosphatases 2, no. 2: 209-223. https://doi.org/10.3390/kinasesphosphatases2020013

APA Style

Nawaz, T., Fahad, S., & Zhou, R. (2024). Protein Phosphorylation Nexus of Cyanobacterial Adaptation and Metabolism. Kinases and Phosphatases, 2(2), 209-223. https://doi.org/10.3390/kinasesphosphatases2020013

Article Metrics

Back to TopTop