TY - JOUR
T1 - Tremorgenic and neurotoxic paspaline-derived indole-diterpenes
T2 - biosynthetic diversity, threats and applications
AU - Kozák, László
AU - Szilágyi, Zoltán
AU - Tóth, László
AU - Pócsi, István
AU - Molnár, István
N1 - Funding Information:
Funding information This work was supported by the European Union and the European Social Fund through the project EFOP-3.6.1-16-2016-00022 (to I. P.), the Higher Education Institutional Excellence Program of the Ministry of Human Capacities in Hungary (Biotechnology thematic program to I. P. and I. M.) and the U.S. National Institutes of Health (NIGMS 5R01GM114418 to I. M.).
Publisher Copyright:
© 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2019/2/15
Y1 - 2019/2/15
N2 - 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.
AB - 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.
KW - Biosynthesis
KW - Drug discovery
KW - Food and feed safety
KW - Fungal secondary metabolite
KW - Heterologous production
KW - Indole-diterpene
KW - Mycotoxin
UR - http://www.scopus.com/inward/record.url?scp=85059675703&partnerID=8YFLogxK
U2 - 10.1007/s00253-018-09594-x
DO - 10.1007/s00253-018-09594-x
M3 - Review Article
C2 - 30613899
AN - SCOPUS:85059675703
SN - 0175-7598
VL - 103
SP - 1599
EP - 1616
JO - Applied Microbiology and Biotechnology
JF - Applied Microbiology and Biotechnology
IS - 4
ER -