Metabolic Engineering of Cyanobacterial Systems

Cyanobacteria harness solar energy to fix atmospheric carbon dioxide through oxygenic photosynthesis, making them attractive platforms for sustainable production of fuels, chemicals and high-value compounds. Metabolic engineering in these organisms integrates synthetic biology, genome editing and computational modelling to rewire native pathways or introduce heterologous routes that channel photosynthate toward target molecules. Strategies include modulation of key enzymes, optimisation of carbon flux between the Calvin–Benson–Bassham cycle and ancillary pathways, elimination of competing sinks and deployment of regulatory switches responsive to light or cellular energy status. Advances in genetic toolboxes have enabled precise, markerless modifications, while systems-level analyses guide rational design and reveal metabolic bottlenecks under photoautotrophic conditions and diurnal cycles. This multidisciplinary effort addresses challenges such as low product titres, photoinhibition and the balancing of growth versus production. Successes range from enhanced secretion of sugars and alcohols to tailored synthesis of terpenoids, fatty acids and bioplastics. The global significance of this field is underscored by its potential to mitigate greenhouse gas emissions, decrease reliance on fossil resources and establish carbon-neutral biomanufacturing platforms.

Research from Nature Portfolio

Recent studies have demonstrated the latent capacity of model cyanobacteria to secrete high-value metabolites purely through phototrophic metabolism. By disabling native glucokinase activity and exploiting spontaneous adaptive mutations, one strain accumulated and exported glucose at multi-gram-per-litre levels without heterologous transporter genes, highlighting metabolic plasticity and the value of minimal interventions. Another investigation uncovered an ATP-sensing phosphoketolase that gates flux into the Calvin–Benson–Bassham cycle; removal of this regulatory enzyme boosted CO₂ fixation by up to 60 % during light–dark transitions and induced sucrose secretion, revealing a conserved allosteric mechanism with broad applicability. Complementing these findings, global rewiring of central carbon metabolism in a fast-growing Synechococcus elongatus strain combined enhancements in glycolytic routes with modifications in the Calvin cycle to drive continuous production of 2,3-butanediol at industrially relevant titres, even under low-light or dark conditions. Together, these advances illustrate how fine-tuning of native regulators and coordinated pathway engineering can unlock new production modes in cyanobacterial platforms.

Metabolic Engineering of Cyanobacterial Systems publication trend

The graph below shows the total number of articles in metabolic engineering of cyanobacterial systems across all publications each year (not limited to Nature Index journals).

Technical terms

Calvin–Benson–Bassham cycle: The set of biochemical reactions by which photosynthetic organisms assimilate CO₂ into organic compounds.

RuBisCO: Ribulose-1,5-bisphosphate carboxylase/oxygenase, the primary enzyme catalysing the first step of CO₂ fixation.

Heterologous expression: Introduction and functional production of genes or pathways from one organism into another.

Phosphoketolase: An enzyme that cleaves sugar phosphates into shorter metabolites, here serving as an ATP-sensitive flux regulator.

Nanofilament: A self-assembling protein filament engineered to organise enzymes within a cell for improved metabolic efficiency.

References

1. Unlocking the potentials of cyanobacterial photosynthesis for directly converting carbon dioxide into glucose. Nature Communications (2023).
2. An ATP-sensitive phosphoketolase regulates carbon fixation in cyanobacteria. Nature Metabolism (2023).
3. Global metabolic rewiring for improved CO2 fixation and chemical production in cyanobacteria. Nature Communications (2017).
4. Self-Assembly of Nanofilaments in Cyanobacteria for Protein Co-localization. ACS Nano (2023).
5. Cyanobacteria: Promising biocatalysts for sustainable chemical production. Journal of Biological Chemistry (2017).