Isoprenoids in eukaryotic phytoplankton: metabolic diversity, eco-physiology and biotechnological opportunities.

Isoprenoids are a diverse group of metabolites essential for algal physiology and ecology, which hold biotechnological potential. Despite recent interest in engineering microalgae for high-value isoprenoid production, understanding of their endogenous biosynthesis and regulatory networks remains fragmented. The major focus, in fact, is still on biotechnological applications rather than physiological relevance. This review bridges this gap by comprehensively evaluating isoprenoid biosynthesis and regulation across diverse microalgal taxa and by examining key differences and similarities between primary metabolic pathways: the chloroplast-localized 2-C-methyl-D-erythritol 4-phosphate (MEP) and cytosolic mevalonate (MVA) pathways. The distinct compartmentalization of these pathways is highlighted, especially in relation to lineage-specific evolutionary trajectories which derive from primary and secondary endosymbiotic events. Unique enzymatic adaptations and lineage-specific carotenoid biosynthesis enzymes make algal isoprenoid metabolism distinct from that of plants, fungi and animals, to reflect their ecology and physiology. Furthermore, we explore emerging evidence on multiple regulatory systems in isoprenoid biosynthesis, such as transcriptional and post-transcriptional regulatory mechanisms, alongside feedback loops and metabolite sensing systems. We discuss the complex interplay between MEP and MVA pathways, especially regarding metabolite crosstalk, differential localization of enzymes, and species-specific metabolic divergence. Using specialized metabolites like sterol sulfates and isoprenoid-derived domoic acid as examples, we highlight unresolved questions regarding isoprenoid ecological functions. Finally, we present synthetic biology strategies harnessing microalgal metabolism for sustainable terpenoid biosynthesis, identifying promising avenues for metabolic engineering and connecting this comprehensive review to the work currently ongoing in isoprenoid biotechnology.