Prodigiosin Biosynthesis and Its Applications in Cancer Therapy

Prodigiosin is a red tripyrrole pigment naturally produced by various Gram-negative bacteria, most notably Serratia marcescens. Biosynthesis relies on a modular gene cluster that orchestrates the assembly of monopyrrolic and bipyrrolic precursors through dedicated enzymes. Advances in synthetic biology have enabled the transfer of this cluster into heterologous hosts such as Pseudomonas putida and Escherichia coli, leading to improved titres and the generation of novel prodiginine derivatives. In parallel, fermentation conditions have been optimised using unconventional substrates—ranging from agricultural by-products to industrial waste streams—to drive cost-effective, large-scale production. Beyond its striking pigment, prodigiosin has garnered attention for selective anticancer activity: it triggers programmed cell death in malignant cells via caspase activation, disrupts autophagic flux through Golgi apparatus perturbation, and generates reactive oxygen species that damage nucleic acids. These multimodal mechanisms confer a therapeutic window by sparing non-malignant cells. Preclinical studies demonstrate significant tumour growth inhibition in animal models, and synergy with established chemotherapeutics is under exploration. Collectively, the convergence of metabolic engineering, process optimisation and mechanistic insights positions prodigiosin as a promising lead for next-generation anticancer agents with global relevance for sustainable drug development.

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Prodigiosin Biosynthesis and Its Applications in Cancer Therapy publication trend

The graph below shows the total number of articles in prodigiosin biosynthesis and its applications in cancer therapy across all publications each year (not limited to Nature Index journals).

Technical terms

Prodigiosin: A linear tripyrrole secondary metabolite with potent bioactivities, including selective anticancer effects.

Biosynthetic gene cluster: A contiguous set of genes encoding the enzymes required for sequential assembly of prodigiosin’s molecular scaffold.

Heterologous expression: Introduction and functional expression of a non-native gene cluster in an alternative microbial host to enhance production.

Apoptosis: Programmed cell death characterised by caspase-mediated proteolysis and DNA fragmentation in cancer cells.

Autophagy: A lysosome-dependent degradation pathway that can be modulated by prodigiosin to impair tumour cell survival.

References

1. The Golgi stacking protein GRASP55 is targeted by the natural compound prodigiosin. Cell Communication and Signaling (2023).
2. Recent advancements in high-level synthesis of the promising clinical drug, prodigiosin. Applied Microbiology and Biotechnology (2019).
3. Efficient recombinant production of prodigiosin in Pseudomonas putida. Frontiers in Microbiology (2015).
4. Prodigiosin Production by Serratia marcescens UCP 1549 Using Renewable-Resources as a Low Cost Substrate. Molecules (2010).
5. Production of Prodigiosin Using Tannery Fleshing and Evaluating Its Pharmacological Effects. The Scientific World JOURNAL (2014).
6. Biological Potential and Mechanism of Prodigiosin from Serratia marcescens Subsp. lawsoniana in Human Choriocarcinoma and Prostate Cancer Cell Lines. International Journal of Molecular Sciences (2018).
7. Serratia Secondary Metabolite Prodigiosin Inhibits Pseudomonas aeruginosa Biofilm Development by Producing Reactive Oxygen Species that Damage Biological Molecules. Frontiers in Microbiology (2016).