Synthetic iminosugar monomers change global metabolic pathways and chitin biosynthesis in Thalassiosira rotula

- Thalassiosira rotula produces extracellular chitin fibers of interest for material science. Tailored monomeric iminosugars, designed as substrate analogues for carbohydrate-active enzymes, unexpectedly elongate these fibers in vivo, yet their impact on chitin metabolism remains unclear. - T.rotula was exposed to three L-isoleucine-derived iminosugar analogues immediately before cell division, when chitin fibers are produced. RNA-sequencing, combined with differential expression and pathway enrichment analyses, as well as transcriptome mining for chitin-related genes was performed. - Gene mining identified 84 chitin-associated genes (including 42 chitin synthases). Two iminosugars globally repressed carbohydrate- and energy-related pathways including photosynthesis, glycolysis/gluconeogenesis, and Calvin cycle while simultaneously inducing ribosome biogenesis. ImOH specifically downregulated 29 chitin-related genes, including two strongly repressed chitinases and a {beta}-N-acetylhexosaminidase. - Tailored monomeric chitin-modulating iminosugars not only alter chitin fiber length but also trigger a broad metabolic shift from carbohydrate synthesis toward ribosome biogenesis, indicative of a cellular stress response to non-metabolizable iminosugars.