Reference - Detail
RRC ID | 12029 |
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Author | Hamaji Y, Fujimori M, Sasaki T, Matsuhashi H, Matsui-Seki K, Shimatani-Shibata Y, Kano Y, Amano J, Taniguchi S. |
Title | Strong enhancement of recombinant cytosine deaminase activity in Bifidobacterium longum for tumor-targeting enzyme/prodrug therapy. |
Journal | Biosci Biotechnol Biochem |
Abstract |
In our previous studies, a strain of the nonpathogenic, anaerobic, intestinal bacterium, Bifidobacterium longum (B. longum), was found to be localized selectively and to proliferate within solid tumors after systemic administration. In addition, B. longum transformed with the shuttle-plasmid encoding the cytosine deaminase (CD) gene expressed active CD, which deaminated the prodrug 5-fluorocytosine (5-FC) to the anticancer agent 5-fluorouracil (5-FU). We also reported antitumor efficacy with the same plasmid in several animal experiments. In this study, we constructed a novel shuttle-plasmid, pAV001-HU-eCD-M968, which included the mutant CD gene with a mutation at the active site to increase the enzymatic activity. In addition, the plasmid-transformed B. longum produces mutant CD and strongly increased (by 10-fold) its 5-FC to 5-FU enzymatic activity. The use of B. longum harboring the new shuttle-plasmid increases the effectiveness of our enzyme/prodrug strategy. |
Volume | 71(4) |
Pages | 874-83 |
Published | 2007-4-1 |
DOI | 10.1271/bbb.60502 |
PII | JST.JSTAGE/bbb/60502 |
PMID | 17420581 |
MeSH | Antimetabolites / metabolism* Antineoplastic Agents / chemistry* Antineoplastic Agents / pharmacology* Bifidobacterium / enzymology* Bifidobacterium / genetics Binding Sites / genetics Blotting, Western Chromatography, High Pressure Liquid Cytosine Deaminase / chemistry* Cytosine Deaminase / genetics Cytosine Deaminase / pharmacology* Flucytosine / metabolism* Fluorouracil / metabolism* Mutation / genetics Plasmids / genetics Prodrugs / chemistry* Prodrugs / pharmacology* Recombinant Proteins / chemistry Recombinant Proteins / pharmacology |
IF | 1.516 |
Times Cited | 21 |
WOS Category | FOOD SCIENCE & TECHNOLOGY CHEMISTRY, APPLIED BIOTECHNOLOGY & APPLIED MICROBIOLOGY BIOCHEMISTRY & MOLECULAR BIOLOGY |
Resource | |
DNA material | pAxCACD pAdex1CACD (RDB1591) |