Biosynthesis of a Neo-epi-verrucosane diterpene in the liverwort Fossombronia alaskana - A retrobiosynthetic NMR study

The biosynthesis of the diterpene 8 alpha-acetoxy-13 alpha-hydroxy-5-oxo-13 -epi-neoverrucosane in the arctic Liverwort Fossombronia alaskana was studi ed by incorporation experiments using [1-C-13]- and [U-C-13(6)]glucose as p recursors. The C-13-labeling patterns of acetyl-CoA, pyruvate, and phosphoe nolpyruvate in intermediary metabolism were reconstructed from the C-13 NMR data of biosynthetic amino acids (leucine, alanine, phenylalanine) and wer e used to predict hypothetical labeling patterns for isopentenyl pyrophosph ate formed via the mevalonate pathway and the deoxyxylulose pathway. The la beling patterns observed for the neoverrucosane diterpene were consistent w ith the intermediate formation of geranyllinaloyl pyrophosphate assembled f rom dimethylallyl pyrophosphate and three molecules of isopentenyl pyrophos phate generated predominantly or entirely via 1-deoxyxylulose 5-phosphate. The experimental data can be integrated into a detailed biosynthetic scheme involving a 1,5-hydride shift. The postulated involvement of the 1,5-hydri de shift was confirmed by an incorporation experiment with [6,6-H-2(2)]gluc ose.