Effect of RNA Demethylase FTO Overexpression on Biomass and Bioactive Substances in Diatom Phaeodactylum tricornutum

<i>Phaeodactylum tricornutum</i> is rich in bioactive substances, rendering it valuable in nutrition and medicine. Epigenetic editing mediated by human RNA demethylase FTO can significantly increase the yields of rice and potato and offers significant potential for the genetic breeding of microalgae. This study aimed to enhance the production of certain metabolites in <i>P. tricornutum</i> via FTO-mediated epigenetic editing. Phenotypic analysis revealed that transgenic <i>P. tricornutum</i> exhibits significantly reduced RNA m⁶A modification levels and faster growth, producing markedly higher levels of lipids, proteins, and carotenoids than the wild type. Transcriptome analysis revealed 1009 upregulated genes and 378 downregulated genes. KEGG analysis demonstrated the upregulated expression of multiple key enzymes involved in long-chain fatty acid synthesis (e.g., ACSL, fabF, and fabG), carotenoid synthesis (e.g., crtQ, PDS, and PSY1), and amino acid synthesis (e.g., dapF, glyA, and aroK) in transgenic <i>P. tricornutum</i>, consistent with our phenotypic results. These results indicate that FTO can promote growth and increase the bioactive compound content in <i>P. tricornutum</i> by regulating the m⁶A modification of RNA, and further suggest that FTO has the potential to serve as a new tool for the epigenetic editing of microalgae.