GENETIC-MODIFICATION OF AN ECHINOCANDIN B-PRODUCING STRAIN OF ASPERGILLUS-NIDULANS TO PRODUCE MUTANTS BLOCKED IN STERIGMATOCYSTIN BIOSYNTHESIS

The production of echinocandin B (ECB), a lipopolypeptide used for che mical manufacture of the anti-Candida agent Cilofungin (TM), was accom plished by fermentation using a strain of Aspergillus nidulans. In add ition 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 creat ed by genetic modification of the polyploid production strain C747. Th e following steps were involved: (i) reduction of the genotype to hapl oid by treatment with the spindle fiber poison methyl 1-(butylcarbomoy l)-2-benzimidazole carbamate (MBC), using colony morphology, conidia s ize, 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 pro duction were isolated. All six remained capable of producing ECB equiv alent in quantity to the haploid strain C747-GR14. One of the mutants was shown to be the result of a chromosomal translocation.