Abiotic Stress-Induced Diversification of Secondary Metabolites in Cyanobacteria: Mechanisms, Biosynthesis and Applications

Abstract

Cyanobacteria, among the earliest oxygenic photosynthetic organisms, exhibit remarkable metabolic versatility that enables them to survive in diverse and extreme environments. A key aspect of this adaptability is their ability to produce a wide range of structurally diverse secondary metabolites. This review provides a comprehensive overview of the role of abiotic stress as a major driver of secondary metabolite diversification in cyanobacteria, with particular emphasis on the underlying molecular mechanisms, biosynthetic pathways and emerging applications. Environmental stressors such as ultraviolet radiation, fluctuations in salinity, nutrient limitation and oxidative stress induce complex cellular responses including signalling mediated by reactive oxygen species (ROS), transcriptional reprogramming and redistribution of metabolic flux. These processes collectively activate biosynthetic gene clusters (BGCs), including cryptic or silent pathways. Advances in omics technologies including genomics, transcriptomics, proteomics and metabolomics, have significantly improved the identification and functional characterization of stress-responsive biosynthetic pathways. The integration of these approaches with synthetic biology and metabolic engineering provides new opportunities for the targeted manipulation of metabolite production and the discovery of novel bioactive compounds. This review also highlights the biotechnological potential of stress-induced metabolites in pharmaceuticals, nutraceuticals, cosmetics and environmental applications. Despite these advances, challenges such as low yield, difficulties in activating silent BGCs and constraints related to scalability still persist. Overall, this review underscores abiotic stress as a powerful regulatory factor for unlocking cyanobacterial biosynthetic potential and advancing sustainable natural product discovery.