Tremorgenic and neurotoxic paspaline-derived indole-diterpenes: biosynthetic diversity, threats and applications

László Kozák, Zoltán Szilágyi, László Tóth, István Pócsi (Corresponding Author), István Molnár (Corresponding Author)

Research output: Contribution to journalReview Articlepeer-review

29 Citations (Scopus)


Indole-diterpenes (IDTs) such as the aflatrems, janthitrems, lolitrems, paspalitrems, penitrems, shearinines, sulpinines, and terpendoles are biogenetically related but structurally varied tremorgenic and neurotoxic mycotoxins produced by fungi. All these metabolites derive from the biosynthetic intermediate paspaline, a frequently occurring IDT on its own right. In this comprehensive review, we highlight the similarities and differences of the IDT biosynthetic pathways that lead to the generation of the main paspaline-derived IDT subgroups. We survey the taxonomic distribution and the regulation of IDT production in various fungi and compare the organization of the known IDT biosynthetic gene clusters. A detailed assessment of the highly diverse biological activities of these mycotoxins leads us to emphasize the significant losses that paspaline-derived IDTs cause in agriculture, and compels us to warn about the various hazards they represent towards human and livestock health. Conversely, we also describe the potential utility of these versatile molecules as lead compounds for pharmaceutical drug discovery, and examine the prospects for their industrial scale manufacture in genetically manipulated IDT producers or domesticated host microorganisms in synthetic biological production systems.

Original languageEnglish
Pages (from-to)1599-1616
Number of pages18
JournalApplied Microbiology and Biotechnology
Issue number4
Publication statusPublished - 15 Feb 2019
MoE publication typeA2 Review article in a scientific journal


  • Biosynthesis
  • Drug discovery
  • Food and feed safety
  • Fungal secondary metabolite
  • Heterologous production
  • Indole-diterpene
  • Mycotoxin


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