On the generation of novel anticancer drugs by recombinant DNA technology:: The use of combinatorial biosynthesis to produce novel drugs

被引:0
作者
Méndez, C
Salas, JA [1 ]
机构
[1] Univ Oviedo, Dept Biol Func, E-33006 Oviedo, Spain
[2] Univ Oviedo, IUOPA, E-33006 Oviedo, Spain
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中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Chemotherapeutic drugs for cancer treatment have been traditionally originated by the isolation of natural products from different environmental niches, by chemical synthesis or by a combination of both approaches thus generating semisynthetic drugs. In the last years, a number of gene clusters from several antitumor biosynthetic pathways, mainly produced by actinomycetes and belonging to the polyketides family, are being characterized. Genetic manipulation of these antitumor biosynthetic pathways will offer in the near future an alternative for the generation of novel antitumor derivatives and thus complementing current methods for obtaining novel anticancer drugs. Novel antitumor derivatives have been produced by targetted gene disruption and heterologous expression of single (or a few) gene(s) in another hosts or by combining genes from different, but structurally related, biosynthetic pathways ("combinatorial biosynthesis"). These strategies take advantage from the "relaxed substrate specificity" that characterize secondary metabolism enzymes.
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页码:513 / 526
页数:14
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共 50 条
[1]   Identification and expression of genes involved in biosynthesis of L-oleandrose and its intermediate L-olivose in the oleandomycin producer Streptomyces antibioticus [J].
Aguirrezabalaga, I ;
Olano, C ;
Allende, N ;
Rodriguez, L ;
Braña, AF ;
Méndez, C ;
Salas, JA .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2000, 44 (05) :1266-1275
[2]  
Arcamone F, 1998, CURR MED CHEM, V5, P391
[3]  
BECHTHOLD A, 1999, COMBINATORIAL ORGANI, P381
[4]   Identification of a sugar flexible glycosyltransferase from Streptomyces olivaceus, the producer of the antitumor polyketide elloramycin [J].
Blanco, G ;
Patallo, EP ;
Braña, AF ;
Trefzer, A ;
Bechthold, A ;
Rohr, J ;
Méndez, C ;
Salas, JA .
CHEMISTRY & BIOLOGY, 2001, 8 (03) :253-263
[5]  
Cragg GM, 1999, CANCER INVEST, V17, P153
[6]   IDENTIFICATION OF STREPTOMYCES-OLIVACEUS TU-2353 GENES INVOLVED IN THE PRODUCTION OF THE POLYKETIDE ELLORAMYCIN [J].
DECKER, H ;
ROHR, J ;
MOTAMEDI, H ;
ZAHNER, H ;
HUTCHINSON, CR .
GENE, 1995, 166 (01) :121-126
[7]   NOVEL GENETICALLY-ENGINEERED TETRACENOMYCINS [J].
DECKER, H ;
HAAG, S ;
UDVARNOKI, G ;
ROHR, J .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION IN ENGLISH, 1995, 34 (10) :1107-1110
[8]   Two new tailoring enzymes, a glycosyltransferase and an oxygenase, involved in biosynthesis of the angucycline antibiotic urdamycin A in Streptomyces fradiae Tu2717 [J].
Faust, B ;
Hoffmeister, D ;
Weitnauer, G ;
Westrich, L ;
Haag, S ;
Schneider, P ;
Decker, H ;
Künzel, E ;
Rohr, J ;
Bechthold, A .
MICROBIOLOGY-UK, 2000, 146 :147-154
[9]   New pharmaceuticals from marine organisms [J].
Fenical, W .
TRENDS IN BIOTECHNOLOGY, 1997, 15 (09) :339-341
[10]  
Fernández E, 1998, J BACTERIOL, V180, P4929