Enzymatic synthesis of actinomycin D and analogues containing N-methylalanine from synthetic pentapeptide lactone precursors.

The actinomycins constitute a family of chromopeptide antibiotics containing an aminophenoxazinone chromophore attached to two pentapeptide lactone units of variable amino acid content1}. It was postulated as early as 1956 that the final step in the biosynthesis of an actinomycin involves the oxidative condensation of two molecules of a 3-hydroxy-4-methylanthraniloyl (4-MHA) peptide lactone2) (Fig. 1). Subsequently, several total