Exploring 2,4-diacetylphloroglucinol: A multifunctional biocontrol and therapeutic potential

Abstract

2,4-Diacetylphloroglucinol (2,4-DAPG) is a polyketide-derived secondary metabolite synthesised primarily by fluorescent Pseudomonas spp., notably P. fluorescens Pf-5, CHA0, and Q2-87. This review comprehensively explores the biosynthetic, genetic, and regulatory frameworks underlying 2,4-DAPG production, along with its broad-spectrum biological activities that bridge agricultural and biomedical significance. Despite extensive documentation of its biocontrol efficacy, research gaps persist regarding its coordinated regulation by the phl gene cluster and global networks such as GacS/GacA and small RNAs (RsmXYZ), which influence metabolite flux under environmental cues. Recent studies highlight its potent antimicrobial, antifungal, antibacterial, nematicidal, antihelminthic, phytotoxic, and plant growth-regulating activities mediated through membrane disruption, inhibition of oxidative phosphorylation, and induction of reactive oxygen species. Its ability to trigger induced systemic resistance (ISR) via jasmonic acid and ethylene pathways enhances plant immunity and crop resilience. Beyond agriculture, 2,4-DAPG exhibits pronounced cytotoxic and anticancer potential, demonstrating selective antiproliferative effects against human lung (A549), breast (MCF-7), and leukaemia (HL-60) cell lines, along with notable anti-inflammatory and antiviral properties. The pro-apoptotic mechanism involves Bax activation and caspase-3 signalling, coupled with inhibition of NF-κB, MAPK1, and WNT1 cascades. To meet the rising demand, future research emphasises metabolic engineering of high-yield Pseudomonas strains, multi-omics-guided metabolic pathway optimisation, heterologous gene expression, and bioreactor-based fermentation for scalable production. In conclusion, 2,4-DAPG represents a multifunctional metabolite with immense potential for sustainable agriculture and therapeutic innovation through large-scale, eco-efficient biomanufacturing.