Cyanobacterial Natural Products as Emerging Antibacterial Agents: Bioactive Compounds and Their Potential to Combat Antimicrobial Resistance

Abstract

Cyanobacteria, commonly known as blue-green algae, represent a chemically diverse group of microorganisms capable of producing a wide range of structurally diverse natural products with considerable biological activity. Their secondary metabolites include peptides, lipopeptides, alkaloids, polyketides, fatty acids, terpenoids, bromophenols, and other bioactive compounds. This review provides an integrated assessment of the phytochemical diversity and antibacterial potential of cyanobacterial natural products, with emphasis on compounds reported from different cyanobacterial genera. Species belonging to Anabaena, Calothrix, Fischerella, Lyngbya, Nostoc, Scytonema, Tolypothrix, and Oscillatoria have been reported to produce metabolites active against both Gram-positive and Gram-negative bacteria. Important antibacterial compounds include circinamide, microginin, puwainaphycin C, calophycin, fischerellins, hassallidins, muscoride A, Scytophycins C, Tolytoxin, Ambigol A, Tjipanazole D, Calothrixin A, Nostocyclyne A, Hapalindole T, and other structurally diverse metabolites. Recent studies further demonstrate antibacterial activity in both established and less-explored cyanobacterial taxa, including Arthrospira fusiformis, Lyngbya majuscula, Lyngbya martensiana, Oxynema thaianum, Oscillatoria, Cylindrospermum, and Loriellopsis. The review also discusses the chemical characteristics of cyanobacterial antibacterial compounds and possible mechanisms of action, including membrane disruption, interference with cell-envelope functions, inhibition of nucleic-acid and protein synthesis, metabolic enzyme inhibition, efflux-pump modulation, and effects on biofilm and quorum-sensing pathways. Recent advances in genome mining, metabolomics, biosynthetic gene-cluster analysis, and synthetic biology further provide opportunities for discovering previously inaccessible cyanobacterial metabolites. Despite this potential, antibacterial activity varies considerably with species, strain, cultivation and extraction conditions, metabolite composition, and target microorganism. Limited mechanistic, toxicity, in vivo, and large-scale production data also remain important challenges. Further bioassay-guided isolation, structural characterization, mechanism-based evaluation, toxicity assessment, and validation against clinically relevant and antimicrobial-resistant bacteria are therefore required. Cyanobacterial natural products represent a promising and expanding chemical resource for the discovery of emerging antibacterial agents and future pharmaceutical development.