| Project/Area Number |
13680676
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Bioorganic chemistry
|
|---|
| Research Institution | Kitasato University |
|---|
Principal Investigator |
IKEDA Haruo Kitasato University, Kitasto Institute for Life Sciences, Professor, 北里生命科学研究所, 教授 (90159632)
|
|---|
| Project Period (FY) |
2001 – 2002
|
| Project Status |
Completed (Fiscal Year 2002)
|
| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
|
|---|
| Keywords | Streptomyces / polyketide / biosynthetic gene / genome analysis / ポリケチド化合物 / エバーメクチン |
|---|
| Research Abstract |
Species of the genus Streptomyces are of major pharmaceutical interest because they synthesize a variety of bioactive secondary metabolites. Especially, the diversity of polyketide compounds observed not only their structures but also their biological activities. Polyketide compounds are synthesized by large multifunctional polypeptide(s). The minimum synthase unit contains β-ketoacylsynthase (KS), acyltransferase (AT), and acyl carrier protein (ACP) to elongation β-keto carbon units. Some synthase unit consist of additional b-carbonyl processing domain(s) b-ketoredutase (KR), dehydratase (DH) or enoylreductase (ER). The composition of β-carbonyl processing domain(s) in each synthase unit reflects the structure of the polyketide backbone. Antiparasitic agent avermectin was produced by Streptomyces avermitilis that was discovered from Japan. We have already cloned entire gene cluster for avermectin biosynthesis with the size of about 85 kb. Within the 90 kb gene cluster for avermectin biosynthesis, the central 65 kb segment was encoded four large multifunctional polyketide synthases. Current recombinant technology is available to introduce a wide variety of specified genetic changes into multifunctional polyketide synthase genes. Avermectin polyketide synthase does not contain ER domain, therefore, fully reduced carbon chains are not found in the polyketide aglycon moiety. We introduced to integrate ER domain gene from other polyketide synthase gene at the module 2 of avermectin PKS aveA1 gene. Resultant recombinants produced small amount of dihydroavermectins. This result is useful for the modification of structure of natural products from Streptomyces strains to improve efficacy and reduction of toxicity.
|
