Biosynthesis of sphinganine-analog mycotoxins

L. Du, X. Zhu, R. Gerber, J. Huffman, L. Lou, J. Jorgenson, F. Yu, K. Zaleta-Rivera, Q. Wang

Research output: Contribution to journalReview article

30 Scopus citations

Abstract

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

Original languageEnglish (US)
Pages (from-to)455-464
Number of pages10
JournalJournal of Industrial Microbiology and Biotechnology
Volume35
Issue number6
DOIs
StatePublished - Jun 1 2008

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

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    Du, L., Zhu, X., Gerber, R., Huffman, J., Lou, L., Jorgenson, J., Yu, F., Zaleta-Rivera, K., & Wang, Q. (2008). Biosynthesis of sphinganine-analog mycotoxins. Journal of Industrial Microbiology and Biotechnology, 35(6), 455-464. https://doi.org/10.1007/s10295-008-0316-y