By Paul Berg (auth.), S. Mongkolsuk, P. S. Lovett, J. E. Trempy (eds.)

Eukaryotic Biotechnology: amendment particular Chromosomal Loci in Mammalian Cells through Recombination (P. Berg). transportable components within the Human Genome (M.F. Singer). Agricultural Biotechnology: Coat Protein Mediated safety and the opportunity of its software in Agriculture (R.N. Beachy). constitution of Peroxidase Isozyme Gene in Brassica and their Expression (A. Shinmyo et al.). Environmental Biotechnology: Environmental keep an eye on of Microbial Gene Expression and Evolution (A.M. Chakrabarty). Bacterial Heavy steel cleansing and Resistance structures (S. Silver). Microbial Biotechnology: Induction of Cat mRNA Translation via Chloramphenicol (P.S. Lovett et al.). purposes of a Multicopy Phenotype strategy (J.E. Trempy). New Technology: research of Epitopes within the Cholera family members of Enterotoxins (M. Kazemi, R.A. Finkelstein). 18 extra articles. Index.

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USA 85,91149118. 14. G. E. (1989) Gene 76, 41-52. 15. , Chen, G. & Palmer, S. (1989) Mol. Biochem. Parasitol. 36,253-262. 16. Chen, G. W. (1987) Mol. Pharmacol. 32, 723-730. 17. Matteucci, M. D. & Caruthers, M. H. (1980) Tetrahedron Letters 21, 719. 18. Matteucci, M. D. & Caruthers, M. H. (1981) J. Am. Chem. Soc. 103, 3185. 19. H. (1981) Tetrahedron Letters 22, 1859. 20. P. , C. (1982) Anal. Biochem. 121, 275-280. 47 21. {1976) Biochem. J. 157, 559-571. 22. Futterman, S. (1957). J. Biol. Chem. 228, 1031-1038.

Unlike antifolate drug resistance in Leishmania (3,4), the mechanism of resistance in Plasmodium has been suggested to be due to a structurally altered enzyme (5-10). Recently, the gene encoding the bifunctional enzyme from P. falciparum has been cloned and isolated from genomic library (11-14). Evidence from the analysis of the DHFR portion of gene obtained from a number of pyrimethamine-resistant strains further supported point mutations of the gene as a mechanism of pyrimethamine resistance (12-15).

We also describe the method by which the recombinant plasmid was genetically manipulated to express different levels of pyrimethamine resistant enzymes. Analysis of the protein products of the genes with regards to their kinetic properties and inhibition by pyrimethamine provides direct evidence of point mutations of the gene as a mechanism of pyrimethamine resistance in P. falciparum. 9 kb Xbal fragment of TS-DHFR (pGemS Xbal) and Biotechrtology and Environmantal Science: Molecular Approaches Edited by S.

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