Biosynthesis of the beta-amino acid moiety of the enediyne antitumor antibiotic C-1027 featuring beta-amino acyl-S-carrier protein intermediates

The delineation of the biosynthesis of the (S)-3-chloro-4,5-dihydroxy-beta-phenylalanine moiety from L-tyrosine and its incorporation into the C-1027 chromophore, which are catalyzed by six enzymes, by in vivo and in vitro studies of five of the six enzymes are reported. A novel strategy for beta-amino acid modification is provided, featuring beta-amino acyl-S-carrier protein intermediates, and also, shed light into engineering the C-1027 biosynthetic machinery for the production of novel analogues as exemplified by 20-deschloro-C-1027 and 20-deschloro-22-deshydroxy-C-1027.