Acyl-homoserine lactone-guided microalgal biotechnology: from metabolic reprogramming to process engineering

Acyl-homoserine lactones (AHLs), the canonical quorum-sensing signals of Gram-negative bacteria, have attracted increasing attention as cross-kingdom regulatory molecules that influence microalgal growth, carbon allocation, redox homeostasis, extracellular organization, and algal-bacterial interactions. However, their potential as predictable regulators of microalgal biotechnology remains uncertain because of limited mechanistic understanding and substantial variability in reported responses. This review critically evaluates AHL chemistry, biosynthesis, environmental fate, quorum quenching, biological responses, and engineering implications, and integrates these aspects into an evidence-based framework for AHL-mediated microalgal regulation. Current evidence indicates that AHL structural features influence physicochemical properties and signal behavior, but a consistent structure-response relationship across microalgal species has not been established. Reported responses depend strongly on effective signal exposure, which is shaped by AHL stability and transformation, quorum-quenching activity, microbial context, cultivation conditions, and physiological state. At the cellular level, AHL exposure is associated with changes in photosynthesis, redox regulation, carbon partitioning, lipid metabolism, and population-level organization. The molecular mechanisms underlying AHL perception in microalgae remain experimentally unresolved. From an engineering perspective, AHL-mediated regulation represents an emerging approach to biological process regulation. Multi-omics, quantitative sensing, machine learning (ML), reactor-scale modelling, and controlled signal delivery may support mechanistic analysis, exposure monitoring, response prediction, and process optimization, although their application to AHL-mediated microalgal systems remains at an early translational stage. Future progress requires standardized AHL quantification, mechanistic validation, microbial-consortium engineering, and reactor-scale verification, together with integrated techno-economic and biosafety assessments to evaluate the reliability and scalability of AHL-mediated strategies for microalgal biotechnology.