From oleaginous microalga to marine chassis: synthetic biology and process-aware biomanufacturing in Nannochloropsis.
Abstract
Nannochloropsis has developed from an oleaginous marine microalga valued mainly for eicosapentaenoic acid (EPA)-rich lipids into a credible candidate for marine photosynthetic biomanufacturing. Its toolkit now spans genome resources, efficient nuclear transformation, homologous recombination, CRISPR/Cas editing, marker recycling, defined integration sites, and modular multigene assembly. Researchers have used these capabilities to alter carbon allocation, triacylglycerol accumulation, EPA synthesis and lipid-class partitioning, carotenoid metabolism, recombinant-protein production, specialty-metabolite formation, and cultivation robustness. This review assesses whether these advances are sufficient to support Nannochloropsis as a predictable, reusable, and process-aware chassis. The evidence shows that the genus has moved beyond basic transformability. Targeted genome modification and pathway construction are feasible, and native and non-native products have reached biologically relevant and, in some cases, process-relevant levels. However, outcomes remain strongly influenced by genomic locus, strain background, intracellular compartment, physiological state, and cultivation regime. Platform maturation will therefore depend on reusable genomic architectures, reliable organelle-targeting rules, dynamic regulation, and phenotyping suited to iterative design-build-test-learn workflows. Strain design must also be coupled more closely to cultivation, harvesting, product recovery, and deployment. Product-specific chassis configurations are likely to be more practical than a universal strain for EPA-rich oils, pigments, recombinant products, and specialty metabolites. Nannochloropsis thus provides a useful test of how an industrially relevant, non-model photosynthetic eukaryote can become a more designable marine production host.