RRC ID 12029
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
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 1.255
Times Cited 16
WOS Category FOOD SCIENCE & TECHNOLOGY CHEMISTRY, APPLIED BIOTECHNOLOGY & APPLIED MICROBIOLOGY BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
DNA material pAxCACD pAdex1CACD (RDB1591)