It is proposed to investigate the biosynthesis of three novel, naturally occurring cyclopentanoid compounds. These are the alkaloid sesbanine, which occurs in the leguminous plant Sesbania drummondii, the antibiotic aristeromycin, and the phytotoxin coronatine. In the case of sesbanine, it is postulated that the alkaloid is derived from nicotinic acid and either phenylalanine, tyrosine, or shikimate. It is further suggested that the cyclopentane ring of the alkaloid is formed by ring contraction of a six-membered ring derived from shikimate or one of the two aromatic amino acids. On the other hand, the cyclopentane ring of aristeromycin is believed to be derived by cyclization of a hexose with the potential intermediacy of myo-inositol. Finally, the hydroindane portion of the phytotoxin coronatine is postulated to be derived from acetate plus one or more aliphatic acids while the cyclopropyl amino acid of the toxin probably arises from isoleucine. The major objective of the work is to establish the biosynthetic origin of the carbon atoms in the skeletons of all three natural products. The method to be utilized is the administration of specifically labeled precursors to the appropriate organisms followed by location of the labels in the natural products by degradation or c.m.r. spectrometry.
| Vos, S; Parry, R J; Burns, M R et al. (1998) Structures of free and complexed forms of Escherichia coli xanthine-guanine phosphoribosyltransferase. J Mol Biol 282:875-89 |
| Krahn, J M; Kim, J H; Burns, M R et al. (1997) Coupled formation of an amidotransferase interdomain ammonia channel and a phosphoribosyltransferase active site. Biochemistry 36:11061-8 |
| Parry, R J; Burns, M R; Skae, P N et al. (1996) Carbocyclic analogues of D-ribose-5-phosphate: synthesis and behavior with 5-phosphoribosyl alpha-1-pyrophosphate synthetases. Bioorg Med Chem 4:1077-88 |
| Kim, J H; Wolle, D; Haridas, K et al. (1995) A stable carbocyclic analog of 5-phosphoribosyl-1-pyrophosphate to probe the mechanism of catalysis and regulation of glutamine phosphoribosylpyrophosphate amidotransferase. J Biol Chem 270:17394-9 |
