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

Echinocandin B (ECB), a lipopolypeptide used as a starting material for che mical manufacture of the anti-Candida agent LY303366, is produced by fermen tation 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-l), which is blocked in ST biosynthe sis, was the result of a chromosomal translocation. The chromosomal regions containing the breakpoints of the translocation were isolated and DNA sequ encing and PCR analysis of the chromosomal breakpoints demonstrated the tra nslocation occurred within the stcW gene of the ST biosynthetic pathway, re sulting in disruption of the open reading frame for this gene. Biochemical feeding studies indicate the involvement of this gene product in the conver sion of averufin to 1-hydroxy versicolorone. This work demonstrates an effe ctive synergy between classical strain improvement methods and molecular ge netics.