Abstract

Cyanobacteria are key organisms in the global ecosystem, useful models for studying metabolic and physiological processes conserved in photosynthetic organisms, and potential renewable platforms for production of chemicals. Characterizing cyanobacterial metabolism and physiology is key to understanding their role in the environment and unlocking their potential for biotechnology applications. Many aspects of cyanobacterial biology differ from heterotrophic bacteria. For example, most cyanobacteria incorporate a series of internal thylakoid membranes where both oxygenic photosynthesis and respiration occur, while CO2 fixation takes place in specialized compartments termed carboxysomes. In this review, we provide a comprehensive summary of our knowledge on cyanobacterial physiology and the pathways in Synechocystis sp. PCC 6803 (Synechocystis) involved in biosynthesis of sugar-based metabolites, amino acids, nucleotides, lipids, cofactors, vitamins, isoprenoids, pigments and cell wall components, in addition to the proteins involved in metabolite transport. While some pathways are conserved between model cyanobacteria, such as Synechocystis, and model heterotrophic bacteria like Escherichia coli, many enzymes and/or pathways involved in the biosynthesis of key metabolites in cyanobacteria have not been completely characterized. These include pathways required for biosynthesis of chorismate and membrane lipids, nucleotides, several amino acids, vitamins and cofactors, and isoprenoids such as plastoquinone, carotenoids, and tocopherols. Moreover, our understanding of photorespiration, lipopolysaccharide assembly and transport, and degradation of lipids, sucrose, most vitamins and amino acids, and haem, is incomplete. We discuss tools that may aid our understanding of cyanobacterial metabolism, notably CyanoSource, a barcoded library of targeted Synechocystis mutants, which will significantly accelerate characterization of individual proteins.

Highlights

  • Cyanobacteria are the only prokaryotes capable of oxygenic photosynthesis

  • While activity of glyoxylate cycle enzymes has been detected in some cyanobacteria, it is unclear whether Synechocystis encodes active variants of isocitrate lyase (Icl) and malate synthase (Msy)

  • Enzymes involved in nucleotide biosynthesis (Figure 5) are highly conserved between E. coli and Synechocystis (Supplementary Table S1), and this pathway has not been investigated in great detail in cyanobacteria

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Summary

Introduction

Cyanobacteria are the only prokaryotes capable of oxygenic photosynthesis. Since their appearance >2.4 billion years ago [1], cyanobacteria have profoundly impacted Earth’s climate and ecosystem, most notably in generation of an oxygenic atmosphere [2]. PCC 6803 (Synechocystis), the most widely studied cyanobacterium, less than 1200 coding sequences (∼30%) have assigned function (469 in metabolism and 115 in transport: Highlighted in red in Supplementary Table S1; ∼558 in other cellular processes (including transposons and transposon related functions): Highlighted in red in Supplementary Table S3), which is less than half compared with Escherichia coli [20]. In Synechocystis, it has been demonstrated that the majority of characterized TM localized proteins are involved in photosynthetic and respiratory energy generation, suggesting that this is the primary function of this compartment [31,32]. These advantages must outweigh potential burdens arising from the additional complexity imposed on the cell. A dense material was observed between this junction that may play a role in ‘attachment’ of the thylakoids to the cell wall but the exact process and the proteins/compounds involved, has not been determined

Central metabolism
Catabolism of glucose and glycogen
Carbon fixation and the Calvin–Benson–Bassham cycle
Photorespiration
Synthesis of carbon storage compounds
The tricarboxylic acid cycle
Fermentation pathways
Chorismate biosynthesis
Metabolism and degradation of nucleotide sugars and sugar osmolytes
Amino acid biosynthesis and degradation
Arginine biosynthesis
Methionine biosynthesis
Histidine biosynthesis
Glutathione biosynthesis
5.10 Iron–sulfur cluster biosynthesis
Nucleotide biosynthesis
Purine biosynthesis
Pyrimidine biosynthesis
Nucleotide salvage pathways
Cofactor biosynthesis
Biotin biosynthesis
Folate biosynthesis
Molybdenum cofactor biosynthesis
Riboflavin and flavin adenine dinucleotide biosynthesis
Thiamine biosynthesis
Pantothenate and coenzyme A biosynthesis
Pyridoxal-5P biosyntheis
Membrane and cell wall biosynthesis
Lipid biosynthesis
Lipoic acid biosynthesis
Peptidoglycan biosynthesis and depolymerization
Lipopolysaccharide biosynthesis
Isoprenoid biosynthesis
Hopene biosynthesis
Carotenoid biosynthesis
Tocopherol biosynthesis
Phylloquinone and plastoquinone biosynthesis
10.1 Haem biosynthesis
10.2 Bilin biosynthesis
10.3 Chlorophyll biosynthesis
10.4 Pseudocobalamin biosynthesis
11. Transport systems
11.2 Amino acid transport
11.3 Metal ion transport
11.3.3 Calcium transport
11.4 Sodium antiporters
11.5 Organic and inorganic carbon transport
Findings
12. Future directions in understanding cyanobacterial metabolism
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