Analysis of biosynthetic enzyme system for dehydrodiketopiperazines with antitumor activity and its application

抗肿瘤脱氢二酮哌嗪生物合成酶体系分析及其应用

• 批准号: 09660095
• 负责人: KANZAKI Hiroshi
• 金额: $ 2.11万
• 依托单位: OKAYAMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09660095/
• 关键词: Albonoursin; bioconversion; dehydrogenation; cyclic dipeptide; cell cycle inhibitor; dehydro amino acid; 細胞分裂阻害物質; Phenylahistin; 細胞周期阻害; 休止菌体反応

Albonoursin production was greatly enhanced when cyclo (L-Leu-L-Phe) (CFL), a tetrahydroderivative of albonoursin, was added to the culture of an albonoursin-producing actinomycete. Furthermore, the resting cells and the cell-free extract of the strain catalyzed the bioconversion of CFL to albonoursin. We isolated and identified the biosynthetic intermediates of this conversion as (Z)-3-benzylidene-6-isobutyl-2, 5-piperazinedione and (Z)-3-benzyl-6-isobutylidene-2, 5-piperazinedione. These results revealed that albonoursin was biosynthesized by dehydrogenation of CFL in the actinomycete. We established the simple assay method for this enzyme activity using phenazine methosulfate and dichlorophenol indophenol as hydrogen acceptors. The cell-free extract was found to catalyze the conversion of several cyclic dipeptides other than CFL to the corresponding dehydro derivatives. Thus, this system might be a powerful tool for producing a variety of dehydro derivatives. Among dehydro cyclic dipeptides prepared, tetradehydro derivatives exhibited an inhibitory activity toward the first cleavage of sea urchin embryo, while didehydro derivatives did not. These facts indicated that dehydrogenation at α, β-positions of both amino acid residues in this type of cyclic dipeptides were required for the inhibitory activity.

当Cyclo（L-Leu-l-Phe）是一种产生的albonoursin ursoduction细胞，静息细胞和无细胞的菌株提取物的生物合成中间体（Z）（Z）的无细胞提取物时-3-苯甲酰苯甲基苯基苯甲酸-6-苯丁烷-2-苯甲酰基-6-苯二苯甲酰基-6-异丁基二硫酸2、5-二膜使用苯丙胺甲硫酸苯甲酸苯酚作为氢苯酚。海胆胚胎的裂解，而didehydro衍生物没有表明抑制活性需要α类型的环状二肽。

项目成果

H. Kanzaki, D. Imura, T. Nitoda, K. Kawazu: "Enzymatic dehydrogenation of cyclo (L-Phe-L-Leu) to a bioactive derivative, albonoursin"Journal of Molecular Catalysis. B, Enzymatic. 6 (3-6). 29-34 (1999)

H. Kanzaki、D. Imura、T. Nitoda、K. Kawazu：“环 (L-Phe-L-Leu) 酶促脱氢为生物活性衍生物 albonoursin”《分子催化杂志》。

Kanzaki, H., Akazawa, K., Imura, D., & Nitoda, T.: "Novel cyclic dipeptide dehydrogenase and assay method for its activity"Scientific Reports of the Faculty of Agriculture Okayama University. 88. 7-11 (1999)

神崎 H.、赤泽 K.、井村 D.、

神崎浩,赤澤和美,井村大輔,仁戸田照彦: "新規の環状ジペプチド脱水素酵素とその活性測定法の確立" 岡山大学農学部学術報告. 87. 13-16 (1999)

Hiroshi Kanzaki、Kazumi Akazawa、Daisuke Imura、Teruhiko Nitoda：“新型环状二肽脱氢酶的建立及其活性测定方法”冈山大学农学部学术报告 87. 13-16 (1999)。

H. Kanzaki, D. Imura, T. Nitoda, K. Kawazu: "Effective production of dehydro cyclic dipeptide albonoursin exhibiting pronuclear fusion inhibitory activity I. Biosynthetic & bioconversion studies"Journal of Antibiotics. 53 (1). 58-62 (2000)

H. Kanzaki、D. Imura、T. Nitoda、K. Kawazu：“有效生产具有原核融合抑制活性的脱氢环状二肽 albonoursin I. 生物合成

Hiroshi Kanzaki, Daisuke Imura, Teruhiko Nitoda & Kazuyoshi Kawazu: "Effective production of dehydro cyclic dipeptide albonoursin exhibiting pronuclear fusion inhibitory activity. II. biosynthetic and bioconversion studies"J. Antibiot.. 53(1). 58-62 (2000

神崎宏、井村大辅、二户田照彦