Analysis of biosynthetic enzyme system for dehydrodiketopiperazines with antitumor activity and its application
| Project/Area Number |
09660095
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
応用微生物学・応用生物化学
|
|---|
| Research Institution | OKAYAMA UNIVERSITY |
|---|
Principal Investigator |
KANZAKI Hiroshi Fac. Agriculture, Okayama Univ., Associate Prof., 農学部, 助教授 (60183787)
|
|---|
| Project Period (FY) |
1997 – 1999
|
| Project Status |
Completed (Fiscal Year 1999)
|
| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1997: ¥1,600,000 (Direct Cost: ¥1,600,000)
|
|---|
| Keywords | 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 |
|---|
| Research Abstract |
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.
|
Report
(4 results)
Research Products
(12 results)
