Catabolism of pyrimidines in yeast:: A tool to understand degradation of anticancer drugs

被引:7
作者
Andersen, G.
Merico, A.
Bjornberg, O.
Andersen, B.
Schnackerz, K. D.
Dobritzsch, D.
Piskur, J.
Compagno, C.
机构
[1] Lund Univ, SE-22362 Lund, Sweden
[2] Tech Univ Denmark, BioCentrum DTU, Lyngby, Denmark
[3] Univ Milan, Dept Biomol Sci & Biotechnol, Milan, Italy
[4] Karolinska Inst, Dept Med Biochem & Biophys, Stockholm, Sweden
[5] Univ Milan, Dept Biomol Sci, Milan, Italy
关键词
uracil degradation; pyrimidines; yeast; evolution; cancer;
D O I
10.1080/15257770600889386
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The pyrimidine catabolic pathway is of crucial importance in cancer patients because it is involved in degradation of several chemotherapeutic drugs, such as 5-fluorouracil; it also is important in plants, unicellular eukaryotes, and bacteria for the degradation of pyrimidine-based biocides/antibiotics. During the last decade we have developed a yeast species, Saccharomyces kluyveri, as a model and tool to study the genes and enzymes of the pyrimidine catabolic pathway. In this report, we studied degradation of uracil and its putative degradation products in 38 yeasts and showed that this pathway was present in the ancient yeasts but was lost approximately 100 million years ago in the S. cerevisiae lineage.
引用
收藏
页码:991 / 996
页数:6
相关论文
共 11 条
[1]   Crystallization and X-ray diffraction analysis of dihydropyrimidinase from Saccharomyces kluyveri [J].
Dobritzsch, D ;
Andersen, B ;
Piskur, J .
ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS, 2005, 61 :359-362
[2]   Crystal structure of dihydropyrimidine dehydrogenase, a major determinant of the pharmacokinetics of the anti-cancer drug 5-fluorouracil [J].
Dobritzsch, D ;
Schneider, G ;
Schnackerz, KD ;
Lindqvist, Y .
EMBO JOURNAL, 2001, 20 (04) :650-660
[3]   PYD2 encodes 5,6-dihydropyrimidine amidohydrolase, which participates in a novel fungal catabolic pathway [J].
Gojkovic, Z ;
Jahnke, K ;
Schnackerz, KD ;
Piskur, J .
JOURNAL OF MOLECULAR BIOLOGY, 2000, 295 (04) :1073-1087
[4]   Dihydropyrimidine amidohydrolases and dihydroorotases share the same origin and several enzymatic properties [J].
Gojkovic, Z ;
Rislund, L ;
Andersen, B ;
Sandrini, MPB ;
Cook, PF ;
Schnackerz, KD ;
Piskur, J .
NUCLEIC ACIDS RESEARCH, 2003, 31 (06) :1683-1692
[5]  
Gojkovic Z, 2001, GENETICS, V158, P999
[6]   Phylogenetic relationships among yeasts of the 'Saccharomyces complex' determined from multigene sequence analyses [J].
Kurtzman, CP ;
Robnett, CJ .
FEMS YEAST RESEARCH, 2003, 3 (04) :417-432
[7]   Yeast β-alanine synthase shares a structural scaffold and origin with dizinc-dependent exopeptidases [J].
Lundgren, S ;
Gojkovic, Z ;
Piskur, J ;
Dobritzsch, D .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (51) :51851-51862
[8]   Yeast genome sequencing:: the power of comparative genomics [J].
Piskur, J ;
Langkjær, RB .
MOLECULAR MICROBIOLOGY, 2004, 53 (02) :381-389
[9]   Purification and characterization of dihydropyrimidine dehydrogenase from Alcaligenes eutrophus [J].
Schmitt, U ;
Jahnke, K ;
Rosenbaum, K ;
Cook, PF ;
Schnackerz, KD .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1996, 332 (01) :175-182
[10]   DEGRADATION OF PURINES AND PYRIMIDINES BY MICROORGANISMS [J].
VOGELS, GD ;
VANDERDRIFT, C .
BACTERIOLOGICAL REVIEWS, 1976, 40 (02) :403-468