Partial reconstruction of the ergot alkaloid pathway by heterologous gene expression in Aspergillus nidulans

Toxins (Basel). 2013 Feb 22;5(2):445-55. doi: 10.3390/toxins5020445.

Abstract

Ergot alkaloids are pharmaceutically and agriculturally important secondary metabolites produced by several species of fungi. Ergot alkaloid pathways vary among different fungal lineages, but the pathway intermediate chanoclavine-I is evolutionarily conserved among ergot alkaloid producers. At least four genes, dmaW, easF, easE, and easC, are necessary for pathway steps prior to chanoclavine-I; however, the sufficiency of these genes for chanoclavine-I synthesis has not been established. A fragment of genomic DNA containing dmaW, easF, easE, and easC was amplified from the human-pathogenic, ergot alkaloid-producing fungus Aspergillus fumigatus and transformed into Aspergillus nidulans, a model fungus that does not contain any of the ergot alkaloid synthesis genes. HPLC and LC-MS analyses demonstrated that transformed A. nidulans strains produced chanoclavine-I and an earlier pathway intermediate. Aspergillus nidulans transformants containing dmaW, easF, and either easE or easC did not produce chanoclavine-I but did produce an early pathway intermediate and, in the case of the easC transformant, an additional ergot alkaloid-like compound. We conclude that dmaW, easF, easE, and easC are sufficient for the synthesis of chanoclavine-I in A. nidulans and expressing ergot alkaloid pathway genes in A. nidulans provides a novel approach to understanding the early steps in ergot alkaloid synthesis.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aspergillus fumigatus / genetics
  • Aspergillus nidulans / genetics*
  • Aspergillus nidulans / metabolism
  • Ergot Alkaloids / genetics*
  • Gene Expression
  • Genes, Fungal / genetics*
  • Mycotoxins / genetics*

Substances

  • Ergot Alkaloids
  • Mycotoxins