This study investigated a sustainable alternative to squalene production utilizing Thraustochytrium sp. and Aurantiochytrium sp., thereby reducing dependence on critically endangered sharks exploited for this compound. By optimizing fed-batch cultivation, a technique prevalent in industrial biotechnology, we have enhanced squalene yields and have demonstrated, through sensitivity analysis, the significance of this shift in preserving species at risk of extinction. Optimization of culture conditions led to the highest biomass concentrations for Thraustochytrium sp. being achieved at lower C–N ratios (<5.0), while the optimal biomass production for Aurantiochytrium sp. occurred in culture media with a high C–N ratio of 54:50. Regarding squalene production, Thraustochytrium sp. produced 26.13 mg/L in the fed-batch system after 72 h, and Aurantiochytrium sp. produced 54.97 mg/L in a batch system with 30 g/L glucose and 0.22 g/L nitrogen after 96 h, showcasing their potential for industrial applications. Moreover, the sensitivity analysis revealed that, on an industrial scale, both strains could produce up to 59.50 t of squalene annually in large-scale facilities, presenting a valuable and sustainable alternative for the biotechnological industry and significantly reducing the reliance on non-renewable and endangered sources such as shark liver oil and preventing the annual capture of over 156,661 sharks.

Microalgae are promising platforms for biomass production, carbon capture, biofuels, and high-value bioproducts. However, despite significant advances in cultivation technologies, reactor engineering, and metabolic engineering, industrial implementation remains limited. This gap suggests that the main challenge of microalgae biotechnology lies not in the availability of productive strains or cultivation systems, but in managing the environmental and physiological heterogeneity that emerges during scale-up. This structured narrative review selected literature using predefined descriptors and relevance-based inclusion criteria and organized the evidence into five thematic domains encompassing cultivation-scale constraints, cellular physiology, bioengineering, precision technologies, and industrial translation. This review examines macrospatial bottlenecks related to light distribution, gas transfer, hydrodynamics, and reactor operation, alongside microspatial constraints involving cell cycle regulation, carbon allocation, metabolic adaptation, and stress responses. Recent advances in adaptive cultivation, real-time monitoring, artificial intelligence, digital twins, computational modeling, and bioengineering are discussed as tools to transform biological and environmental variability into actionable information. Based on concepts established in precision agriculture, this review proposes precision microalgae as a conceptual framework that integrates reactor engineering and cell physiology with three operational pillars: real-time monitoring, predictive modeling, and adaptive control. Its specific contribution is to connect currently fragmented technological and biological advances within a common framework for managing multiscale heterogeneity during cultivation and scale-up. Overall, the available evidence supports the operational logic of this framework, although its generalized effectiveness under industrial conditions remains to be demonstrated.