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<p>Microbial synthetic biology seeks to engineer bacterial genomes for industrial and biomedical applications, typically by applying heterologous gene expression in well-characterized model organisms, such as <i>Escherichia coli</i>. However, heterologous gene expression might cause metabolic disruptions, thereby impacting production efficiency and yield. In this Review, we highlight non-model organisms, such as <i>Lacticaseibacillus</i> and pseudomonads, for endogenous compound production, taking advantage of their evolutionary optimization for the production of certain metabolites and proteins. We first outline key limitations of heterologous production and then examine endogenous production pathways in non-model organisms for biotechnological and therapeutic applications. In particular, multi-omics approaches enable the discovery and characterization of these organisms, and phage-based genome refactoring enhances genome engineering capabilities. Finally, we outline key bottlenecks in the application of non-model organisms in biotechnology, including scale-up, costs and safety.</p>

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Non-model bacteria as platforms for endogenous gene expression in synthetic biology

  • 期刊论文

  • 发表日期：

    2025年9月24日

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  • Jorien Poppeliers,
  • Maarten Boon,
  • Marjan De Mey,
  • Joleen Masschelein,
  • Rob Lavigne

摘要

Microbial synthetic biology seeks to engineer bacterial genomes for industrial and biomedical applications, typically by applying heterologous gene expression in well-characterized model organisms, such as Escherichia coli. However, heterologous gene expression might cause metabolic disruptions, thereby impacting production efficiency and yield. In this Review, we highlight non-model organisms, such as Lacticaseibacillus and pseudomonads, for endogenous compound production, taking advantage of their evolutionary optimization for the production of certain metabolites and proteins. We first outline key limitations of heterologous production and then examine endogenous production pathways in non-model organisms for biotechnological and therapeutic applications. In particular, multi-omics approaches enable the discovery and characterization of these organisms, and phage-based genome refactoring enhances genome engineering capabilities. Finally, we outline key bottlenecks in the application of non-model organisms in biotechnology, including scale-up, costs and safety.