Enzymatic conversion of cyclic dipeptides to dehydro derivatives that inhibit cell division

The cell-free extract of an albonoursin-producing strain, Streptomyces albu lus KO-23, was found to catalyze the conversion of several cyclic dipeptide s having Phe and aliphatic side chain-containing amino acid residues to the corresponding dehydro derivatives. 3Z-Benzylidene-6S-methyl-2,5-piperazine dione, 3Z-benzylidene-2,5-piperazinedione, and 3Z, 6Z-dibenzylidene-2,5-pip erazinedione were prepared by this conversion system. Among the dehydro cyc lic dipeptides prepared, tetradehydro derivatives exhibited inhibitory acti vity toward the first cleavage of sea urchin embryo, while didehydro deriva tives did not. We previously found that cyclo(Leu-Phe) and its didehydro de rivatives did not show any inhibitory activity, in contrast to high activit y in the case of albonoursin. Taken together, these findings indicate that dehydrogenation at the alpha,beta-positions of both amino acid residues in this type of cyclic dipeptide is required for the inhibitory activity.