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 β- 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.