Genetic modification of an echinocandin B-producing strain of Aspergillus nidulans to produce mutants blocked in sterigmatocystin biosynthesis

R. L. Hodges, D. W. Hodges, K. Goggans, X. Xuei, P. Skatrud, D. McGilvray

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

The production of echinocandin B (ECB), a lipopolypeptide used for chemical manufacture of the anti-Candida agent CilofunginTM, was accomplished by fermentation using a strain of Aspergillus nidulans. In addition to ECB, this fermentation also produces a significant amount of sterigmatocystin (ST), a potent carcinogen structurally related to the aflatoxins. Mutants blocked in the ST biosynthetic pathway were created by genetic modification of the polyploid production strain C747. The following steps were involved: (i) reduction of the genotype to haploid by treatment with the spindle fiber poison methyl 1-(butylcarbamoyl)-2-benzimidazole carbamate (MBC), using colony morphology, conidia size, and the ability to obtain 5-fluoro-orotic acid (5-FOA)-resistant mutants as criteria for ploidy; (ii) mutagenesis of a haploid isolate using UV irradiation; and (iii) screening of mutants for inability to produce ST by thin layer chromatography. Six mutants blocked in ST production were isolated. All six remained capable of producing ECB equivalent in quantity to the haploid strain C747-GR14. One of the mutants was shown to be the result of a chromosomal translocation.

Original languageEnglish (US)
Pages (from-to)372-381
Number of pages10
JournalJournal of Industrial Microbiology
Volume13
Issue number6
DOIs
StatePublished - Nov 1 1994
Externally publishedYes

Keywords

  • Aflatoxin
  • CHEF gel
  • Echinocandin
  • Fungi
  • Mutagenesis
  • Sterigmatocystin

ASJC Scopus subject areas

  • Applied Microbiology and Biotechnology

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