Characterization of an echinocandin B-producing strain blocked for sterigmatocystin biosynthesis reveals a translocation in the stcW gene of the aflatoxin biosynthetic pathway

R. L. Hodges, H. S. Kelkar, X. Xuei, P. L. Skatrud, N. P. Keller, T. H. Adams, R. E. Kaiser, V. A. Vinci, D. McGilvray

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Echinocandin B (ECB), a lipopolypeptide used as a starting material for chemical manufacture of the anti-Candida agent LY303366, is produced by fermentation using a strain of Aspergillus nidulans. In addition to ECB, the wild-type strain also produces a significant level of sterigmatocystin (ST), a potent carcinogen structurally related to the aflatoxins. Characterization of a mutant designated A42355-OC-1 (OC-1), which is blocked in ST biosynthesis, was the result of a chromosomal translocation. The chromosomal regions containing the breakpoints of the translocation were isolated and DNA sequencing and PCR analysis of the chromosomal breakpoints demonstrated the translocation occurred within the stcW gene of the ST biosynthetic pathway, resulting in disruption of the open reading frame for this gene. Biochemical feeding studies indicate the involvement of this gene product in the conversion of averufin to 1-hydroxy versicolorone. This work demonstrates an effective synergy between classical strain improvement methods and molecular genetics.

Original languageEnglish (US)
Pages (from-to)333-341
Number of pages9
JournalJournal of Industrial Microbiology and Biotechnology
Volume25
Issue number6
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

Keywords

  • Aflatoxin
  • Aspergillus nidulans
  • Echinocandin B
  • Mutagenesis
  • Sterigmatocystin
  • Translocation

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

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