ASPERGILLUS-NIDULANS STCL ENCODES A PUTATIVE CYTOCHROME-P-450 MONOOXYGENASE REQUIRED FOR BISFURAN DESATURATION DURING AFLATOXIN STERIGMATOCYSTIN BIOSYNTHESIS/

The Aspergillus nidulans stcL gene is predicted to encode a cytochrome P-450 monooxygenase and is located within a cluster of other genes th at are required for synthesis of sterigmatocystin. Inactivation of stc L resulted in strains that accumulate dihydrosterigmatocystin, a tetra hydrobisfuran containing molecule that is very similar to the unsatura ted product of the wild-type pathway, sterigmatocystin. This observati on led us to hypothesize that the A. nidulans sterigmatocystin biosynt hetic pathway is branched similarly to the aflatoxin pathway in Asperg illus parasiticus and Aspergillus flavus and that StcL is required for the desaturation of the bisfuran moiety in the sterigmatocystin/aflat oxin precursor versicolorin B. This prediction was confirmed by feedin g the stcL mutant with the subsequent pathway intermediate, versicolor in A, which resulted in accumulation of both sterigmatocystin and dihy drosterigmatocystin, indicating that StcL functions before versicolori n A synthesis. A. nidulans stcU was shown previously to encode a ketor eductase required to convert versicolorin A to demethylsterigmatocysti n and an stcL, stcU double mutant strain was shown here to accumulate only versicolorin E. These results indicate that both versicolorin A a nd versicolorin B can serve as substrates for StcU, resulting in a bra nched pathway. The final product of each branch are sterigmatocystin a nd dihydrosterigmatocystin, respectively.