Amino acid starter unit in the biosynthesis of macrolactam polyketide antitumor antibiotic vicenistatin

Biosynthetic studies on the starter unit of antitumor antibiotic vicenistatin were undertaken by feeding experiments with (2S,3R)- and (2S,3S)-3-[2H3]methylaspartate, and 3-amino-2-[2H3]methylpropionate. The starter unit of the macrolactam part of vicenistatin was found to be derived from (2S,3S)-3-methylaspartate, but not from the (2S,3R)-isomer. The present as well as the previous results suggest that the starter is formed from l-glutamate through structural rearrangement catalyzed by glutamate mutase to (2S,3S)-3-methylaspartate, which in turn is loaded to polyketide synthase. Additional epimerization and decarboxylation may take place in the process either of activation or condensation to give the final C-18 stereochemistry.