Metabolism of tryptophan by Pseudomonas aureofaciens. 3. Production of substituted pyrrolnitrins from tryptophan analogues.

Exogenous tryptophan is metabolized by Pseudomonas aureofaciens to yield pyrrolnitrin [3-chloro-4-(2'-nitro-3'-chlorophenyl)-pyrrole], an antifungal agent. The ability of this culture to metabolize tryptophan analogues in a similar manner was investigated by addition of the appropriate compound to the fermentation. Tryptophan precursors and metabolites or nonphenyl-substituted tryptophans had little effect on pyrrolnitrin biosynthesis, but simple derivatives of indole inhibited the production of pyrrolnitrin. Tryptophans substituted at the 4 position decreased pyrrolnitrin production and were converted into the corresponding substituted indoles. Tryptophans substituted at the 5, 6, and 7 position with fluorine or at the 5 and 7 position with methyl yielded new pyrrolnitrin derivatives. Substitution of larger groups (such as chloro, bromo, trifluoromethyl, and methoxy) at these positions led to the formation of the intermediate, amino pyrrolnitrin [3-chloro-4-(2'-amino-3'-chlorophenyl)-pyrrole], with the appropriate new substituent. The trifluoromethyl group at the 6 position of tryptophan prevented chlorination at the 3 position of pyrrolnitrin.