Studies on a new biosynthetic pathway for menaquinone (vitamin K)
| Project/Area Number |
17380075
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Bioproduction chemistry/Bioorganic chemistry
|
|---|
| Research Institution | Tokyo University of Agriculture |
|---|
Principal Investigator |
SETO Haruo Tokyo University of Agriculture, Faculty of Applied Bioscience, Professor (10013335)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SUE Masayuki Tokyo University of Agriculture, Faculty of Applied Bioscience, 講師 (10328544)
DAIRI Toru Toyama Prefectural University, Biotechnology Research Center, Associate Professor (70264679)
|
|---|
| Project Period (FY) |
2005 – 2007
|
| Project Status |
Completed (Fiscal Year 2007)
|
| Budget Amount *help |
¥13,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2007: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2006: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥6,500,000 (Direct Cost: ¥6,500,000)
|
|---|
| Keywords | menauumone / vitamin K / Streptomyces coelicolor / biosynthetic intermediates / blocked mutants / Helicobacter pylori / Cambylobacter jejunj / Streptomyces sp. CL190 / 生合成 / メナキノン生合成経路 / ホスホエノールピルビン酸 / エリスロース |
|---|
| Research Abstract |
We found that some pathogenic bacteria including Helicobacter pylori and Campylobacter jejuniutilized a new biosynthetic pathway for menaquinone. This pathway is also present in the genus Streptomyces and branches from the well known menaquinone biosynthetic pathway at chorismate. Since this pathway does not present in human, its inhibitors are expected to be useful as antibacterial substances. In order to reveal the details of this pathway, we carried out the following experiments.
1. At the onset of the experiments, we established unequivocal assignment of 13C-N1VIR spectrum of menaquinone.
2. Labeling experiments using glucoses labeled by^<13>C at different position proved that menaquinone was formed from erythrose, phosphoenolpyruvate and two different C_2 units originating from C5-C6 of glucose.
3. Several kinds of blocked mutants of Streptomyces coelicolor that required menaquinone for their growth were prepared.
4. Based on the results obtained by labeling experiments, 1,4-naphthoquinone-6-carboxylic acid was assumed to be a biosynthetic intermediate of the new pathway. Therefore, we prepared this acid by oxidation of naphthalene-2-carboxylic acid by using Ce(SO_4)_2. This compound enabled the growth of a menaquinone auxotroph of S coelicolor indicating that the synthetic compound is a true intermediate of the new pathway.
5. By detailed investigation of metabolites accumulated by mutants of S coelicolor a nucleoside compound, futalosine, was isolated. This compound consisted of inosine and a m-substituted benzoic acid derivative, and had been isolated from another strain of Streptomyces as an antitumor substance. This compound was proved to be a biosynthetic intermediate of the new pathway, since it supported the growth of some menaquinone auxotrophs of S coelicolor.
6. By utilizing other menaquinone auxotrophs of S coelicolor, several intermediates after futalosine were identified.
|
Report
(4 results)
Research Products
(8 results)
-
-
[Journal Article] Studies on a new biosynthetic pathway for menaquinone2008
Author(s)
H., Seto, Y., Jinnai, T., Hiratsuka, M., Fukawa, K., Furihata, N., Itoh, T., Dairi
-
Journal Title
J. Amer. Chem. Soc 130
Pages: 5614-5615
Description
「研究成果報告書概要(欧文)」より
Related Report
-
-
-
[Presentation] Studies on a new biosynthetic pathway for menaquinone2008
Author(s)
M., Fukawa, Y., Jinnai, T., Hiratsuka, K., Furihata, S., Itoh, T., Dairi
Organizer
National Meeting of Japan Society for Bioscience, Biotechnology, and Agrochemistry
Place of Presentation
Meijo University, Nagoya
Year and Date
2008-03-28
Description
「研究成果報告書概要(欧文)」より
Related Report
-
-
-
