Reverse prenyl transferases exhibit poor facial discrimination in the biosynthesis of paraherquamide A, brevianamide A, and austamide

The mode of attachment of dimethylallyl pyrophosphate (DMAPP) in the biosynthesis of the indole alkaloids paraherquamide A, austamide, and brevianamide A has been studied. Feeding experiments or, Penicillium fellutanum, Penicillium brevicompactum, and Aspergillus ustus using [C-13(2)]-acetate showed isotopic scrambling of the geminal methyl groups originating from C-2 of the indole ring precursors in paraherquamide A, brevianamide A, and austamide biosynthesis. The labeling patterns suggest that the methyl groups of dimethylallyl pyrophosphate become equivalent during the biosyntheses; a non-face-selective, S-N' mechanism has been invoked to account for these observations.