The marine diatom Phaeodactylum tricornutum as a versatile bioproduction chassis: Current progress, challenges, and perspectives.

Beyond its importance in diatom studies, the marine model diatom Phaeodactylum tricornutum has emerged as a versatile photosynthetic chassis for sustainable bioproduction, enabling the production of both native bioactive metabolites and engineered heterologous compounds through synthetic biology. Over the past three decades, transformative advances in the development of genetic tools, including transgenic element optimization, CRISPR-Cas genome editing, and high-efficiency transformation systems, have enabled the engineering of strains for increased fucoxanthin, fatty acid, and triacylglycerol yields and the successful synthesis of diverse heterologous products, from terpenoids and therapeutic peptides to sustainable materials. At the same time, advances in molecular toolkits have refined chassis optimization by revealing the fundamental biological mechanisms underlying nutrient uptake, environmental stress adaptation, stimulus perception, and cell development. Despite this progress, critical challenges persist, particularly suboptimal product yields, biomass limitations, and prohibitive production costs, which hinder industrial translation. In this review, we examine emerging strategies, such as chloroplastic gene expression, DNA site-specific integration, and trophic alteration, that show promise for species improvement; we also address other scale-up considerations, including cultivation strategies, techno-economic analysis, and regulatory policies. Integrated efforts could accelerate the transition of P. tricornutum from a model diatom to a scalable, eco-friendly biomanufacturing platform.