Microbial models of mammalian metabolism. Biotransformations of N-methylcarbazole using the fungus Cunninghamella echinulata.

The fungal metabolism of N-methylcarbazole (NMC) was investigated during the development of microbial models of mammalian metabolism. NMC was metabolized by the fungus Cunninghamella echinulata (ATCC 9244) to generate four metabolites: carbazole, N-hydroxymethylcarbazole (NHMC), 3-hydroxycarbazole, and 3-hydroxy-NHMC. Carbazole and NHMC are two major metabolites previously identified in mammalian systems, while 3-hydroxycarbazole and 3-hydroxy-NHMC have not been previously reported as metabolites of NMC. Structural identification of the four metabolites was based upon spectral (UV, MS, and NMR) and chromatographic (TLC and HPLC) comparisons with synthetic standards. These studies demonstrate that C. echinulata catalyzes the two principal biotransformations observed in mammalian systems with NMC: aliphatic hydroxylation to yield the (relatively) stable carbinolamine NHMC (with slow decomposition to the N-dealkylated product, carbazole) and aromatic hydroxylation in the 3-position.