Biosynthetic intermediates of the tetradehydro cyclic dipeptide albonoursin produced by Streptomyces albulus KO-23.
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 compounds were newly formed prior to albonoursin synthesis in the reaction mixture. These compounds were isolated and identified as (Z)-3-benzylidene-6-isobutyl-2,5-piperazinedione (4) and (Z)-3-benzyl-6-isobutylidene-2,5-piperazinedione (3). The cell-free extract also catalyzed the conversion of compound 3 or 4 to albonoursin. From these results, albonoursin was found to be biosynthesized via these compounds from 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 alpha,beta-positions of both amino acid residues in diketopiperazines is required for cytotoxicity.
Kanzaki
H
H
Laboratory of Bioresources Chemistry, Faculty of Agriculture, Okayama University, Japan.
Yanagisawa
S
S
Nitoda
T
T
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002474:Cell-Free System; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000187:drug effects; D010879:Piperazines / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D012617:Sea Urchins / Q000196:embryology; D013057:Spectrum Analysis; D013302:Streptomyces / Q000737:chemistry*
D000900:Anti-Bacterial Agents; D010879:Piperazines; C006442:albonoursin