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<p>Cyanobacteria are among the oldest photoautotrophic organisms and are recognized as key producers of structurally diverse secondary metabolites with significant pharmacological relevance. These organisms synthesize a wide range of bioactive compounds, including anticancer, neuroactive, anti-inflammatory, and antimicrobial metabolites, many of which exhibit unique mechanisms of action. Despite this potential, practical exploitation of cyanobacterial metabolites has historically been limited by slow growth rates, low product yields, and the frequent transcriptional silence of biosynthetic gene clusters under laboratory conditions. Recent advances in synthetic biology and metabolic engineering have begun to address these challenges. Tools such as CRISPR-based genome regulation, modular cloning platforms, optogenetic control systems, and heterologous expression strategies now enable targeted activation, regulation, and optimization of cyanobacterial biosynthetic pathways. These approaches facilitate access to cryptic metabolites, improve pathway control, and enhance production efficiency, thereby increasing the programmability of cyanobacterial systems. This review integrates current knowledge of cyanobacterial metabolite diversity with recent developments in pathway engineering, regulatory control, and systems-level optimization. Comparative evaluation of microbial production hosts highlights that cyanobacteria are not universal replacements for established heterotrophic systems but occupy complementary niches where photoautotrophic growth, low-input cultivation, and sustainability provide strategic advantages. We further discuss emerging opportunities for decentralized and small-batch biomanufacturing, while critically examining key technical, biosafety, and regulatory barriers that constrain translational deployment. Overall, advances in synthetic biology are progressively transforming cyanobacteria from underexplored natural product sources into programmable platforms for sustainable, biomarker-guided, and precision-oriented therapeutic manufacturing. Continued integration of engineering tools, bioprocess optimisation, and regulatory frameworks will be essential to expand the translational potential of cyanobacterial systems.</p> Graphical abstract <p></p>

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Harnessing engineered cyanobacteria for next-generation therapeutics

  • 期刊论文

  • 发表日期：

    2026年3月17日

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  • Alka Bhardwaj,
  • Arun Kumar Mishra

摘要

Cyanobacteria are among the oldest photoautotrophic organisms and are recognized as key producers of structurally diverse secondary metabolites with significant pharmacological relevance. These organisms synthesize a wide range of bioactive compounds, including anticancer, neuroactive, anti-inflammatory, and antimicrobial metabolites, many of which exhibit unique mechanisms of action. Despite this potential, practical exploitation of cyanobacterial metabolites has historically been limited by slow growth rates, low product yields, and the frequent transcriptional silence of biosynthetic gene clusters under laboratory conditions. Recent advances in synthetic biology and metabolic engineering have begun to address these challenges. Tools such as CRISPR-based genome regulation, modular cloning platforms, optogenetic control systems, and heterologous expression strategies now enable targeted activation, regulation, and optimization of cyanobacterial biosynthetic pathways. These approaches facilitate access to cryptic metabolites, improve pathway control, and enhance production efficiency, thereby increasing the programmability of cyanobacterial systems. This review integrates current knowledge of cyanobacterial metabolite diversity with recent developments in pathway engineering, regulatory control, and systems-level optimization. Comparative evaluation of microbial production hosts highlights that cyanobacteria are not universal replacements for established heterotrophic systems but occupy complementary niches where photoautotrophic growth, low-input cultivation, and sustainability provide strategic advantages. We further discuss emerging opportunities for decentralized and small-batch biomanufacturing, while critically examining key technical, biosafety, and regulatory barriers that constrain translational deployment. Overall, advances in synthetic biology are progressively transforming cyanobacteria from underexplored natural product sources into programmable platforms for sustainable, biomarker-guided, and precision-oriented therapeutic manufacturing. Continued integration of engineering tools, bioprocess optimisation, and regulatory frameworks will be essential to expand the translational potential of cyanobacterial systems.

Graphical abstract