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. Author manuscript; available in PMC: 2026 Feb 1.
Published in final edited form as: Nat Rev Microbiol. 2024 Oct 7;23(2):106–121. doi: 10.1038/s41579-024-01103-4

Fig. 3. Klebsiella oxytoca produces enterotoxins tilimycin and tilivalline.

Fig. 3.

a) A nonribosomal peptide synthetase (NRPS) pathway composed of the three proteins NpsA, ThdA and NpsB, releases ʟ-N-(3-hydroxyanthraniloyl) prolinal, which undergoes spontaneous cyclization to tilimycin diastereomers. Tilivalline is the product of nonenzymatic condensation of the tilimycin dehydration product with indole. Letters in circles indicate adenylation (A), thiolation (T), condensation (C) and thioester-reductase (Re) domains of NRPS proteins. b) Tilivalline binds and stabilizes microtubules, leading to increased polymerization of tubulin into microtubules within asters, which are a structural component of the cell made of microtubules constructed immediately preceding mitosis. Tilivalline ultimately leads to downstream mitotic arrest. c) Tilimycin, a known DNA alkylator, permeates colonic crypts and causes colonic somatic mutations following prolonged exposure.