Kanzaki H, Yanagisawa S, Nitoda T
Laboratory of Bioresources Chemistry, Faculty of Agriculture, Okayama University, Japan.
J Antibiot (Tokyo). 2000 Nov;53(11):1257-64. doi: 10.7164/antibiotics.53.1257.
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.
产白色诺卡氏素的菌株白色链霉菌KO - 23的无细胞提取物催化环（L - 亮氨酸 - L - 苯丙氨酸）（1）转化为白色诺卡氏素（2）。在该转化的早期阶段，在反应混合物中白色诺卡氏素合成之前新形成了两种化合物。这些化合物被分离并鉴定为（Z）-3 - 亚苄基 - 6 - 异丁基 - 2,5 - 哌嗪二酮（4）和（Z）-3 - 苄基 - 6 - 异亚丁基 - 2,5 - 哌嗪二酮（3）。该无细胞提取物还催化化合物3或4转化为白色诺卡氏素。从这些结果可知，发现白色诺卡氏素是由环（L - 亮氨酸 - L - 苯丙氨酸）通过这些化合物生物合成的。与白色诺卡氏素较高的细胞毒性相反，这些二脱氢二酮哌嗪对海胆胚胎的第一次卵裂没有抑制活性，这表明二酮哌嗪中两个氨基酸残基的α，β位脱氢是细胞毒性所必需的。
