2007 Fiscal Year Final Research Report Summary
Genetic engineering of reveromycin A biosynthetic gene cluster and creation of its derivatives
| Project/Area Number |
18580085
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied microbiology
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| Research Institution | The Institute of Physical and Chemical Research |
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Principal Investigator |
TAKAHASHI Shunji The Institute of Physical and Chemical Research, Antibiotics Laboratory, Senior Research Scientist (30311608)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Reveromycin A / Polyketide / P450 |
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| Research Abstract |
Reveromycin A, which is a polyketide compound produced by Streptomyces reveromyceticus, inhibits bone resorption by inducing apoptosis specifically in osteoclasts. To obtain new bioactive derivatives of reveromycin A, the cloning of reveromycin A biosynthetic gene cluster was conducted. Based on the information from mRNA expression pattern and genome shotgun sequencing data, the polyketide biosynthetic gene cluster responsible for reveromycin A biosynthesis was obtained from S. reveromyceticus genome. The sequence analysis revealed the additional polyketide starter module that incorporates methylmalonyl CoA. This suggests that reveromycin A is biosynthesized with additional propionate unit. Interestingly, the reveromycin derivative (reveromycin A2) supporting the DNA sequence information was isolated from the secondary metabolites from S. reveromyceticus. In the biosynthetic gene cluster, P450 which catalyzes the C-18 hydroxylation of reveromycin biosynthetic intermediate was identified. Because the enzyme is a target protein to create reveromycin A derivatives, the crystal graphic analysis is now in progress. The function of unknown genes in the cluster is also investigated through biochemical analysis and gene knock out.
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