The cell-free extract of an albonoursin-producing strain Streptomyces albulus KO-23 catalyzes the conversion of cyclo(L-Leu-L-Phe) (1) to albonoursin (2). At the early stage of this conversion, two compoundswere newly formed prior to albonoursin synthesis in the reaction mixture. These compounds were isolated and identified as (Z)-3-benzylidene-6-isobutyl-2,5piperazinedione (4) and (Z)-3-benzyl-6-isobutylidene-2,5-piperazineciione (3). The cell-free extract also catalyzed the conversion of compound3 or 4 to albonoursin. From these results, albonoursin was found to be biosynthesized via these compoundsfrom cyclo(L-Leu-L-Phe). These didehydro diketopiperazines exhibited no inhibitory activity toward the first cleavage of sea urchin embryo in contrast to the higher cytotoxicity for albonoursin, indicating that dehydrogenation at a,/3-positions of both amino acid residues in diketopiperazines is required for cytotoxicity.
effectively prepared from a fungal metabolite (-)-phenylahistin by the enzymatic conversion catalyzed by the cell-free extract of Streptomyces albulus KO-23, an albonoursin-producing the first cleavage of sea urchin embryos as (-)-phenylahisitn which has been reported to be promising leading compound for anticancer drugs.
Cyclo(His-Phe) was effectively converted to its dehydro derivatives by the enzyme of Streptomyces albulus KO-23, an albonoursin-producing actinomycete. Two types of dehydro derivatives were isolated from the reaction mixture and identified as cyclo(ÁHis-ÁPhe) and cyclo(His-ÁPhe). This is the first report on cyclo-(His-ÁPhe) and the enzymatic preparation of both compounds. Cyclo(ÁHis-ÁPhe), a tetradehydro cyclic dipeptide, exhibited a minimum inhibitory concentration of 0.78 mol/ml inhibitory activity toward the first cleavage of sea urchin embryos, in contrast to cyclo-(His-ÁPhe) that had no activity. The finding that the isoprenylated derivative of cyclo(ÁHis-ÁPhe), dehydrophyenylahistin, had 2,000 times higher activity than cyclo(ÁHis-ÁPhe) indicates that an isoprenyl group attached to an imidazole ring of the compound was essential for the inhibitory activity.
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