Biosynthesis of sphinganine-analog mycotoxins.

摘要: Sphinganine-analog mycotoxins (SAMT) are polyketide-derived natural products produced by a number of plant pathogenic fungi and among the most economically important mycotoxins. The toxins structurally similar to sphinganine, key intermediate in biosynthesis ceramides sphingolipids, competitive inhibitors for ceramide synthase. inhibition sphingolipid is associated with several fatal diseases domestic animals esophageal cancer neural tube defects humans. SAMT contains highly reduced, acyclic polyketide carbon backbone, which assembled single module involves unique chain-releasing mechanism, pyridoxal 5'-phosphate-dependent enzyme catalyzes termination, offloading elongation chain. This leads introduction new carbon-carbon bond an amino group mechanism fundamentally different from thioesterase/cyclase-catalyzed chain releasing found bacterial other fungal biosynthesis. Genetic data suggest that ketosynthase domain synthase controlling final product structure. In addition, post-polyketide modifications have take place before become mature toxins.