Bacterial fatty-acid biosynthesis: a genomics-driven target for antibacterial drug discovery

被引:126
作者
Payne, DJ [1 ]
Warren, PV [1 ]
Holmes, DJ [1 ]
Ji, YD [1 ]
Lonsdale, JT [1 ]
机构
[1] GlaxoSmithKline, Bioinformat, Collegeville, PA 19426 USA
关键词
D O I
10.1016/S1359-6446(01)01774-3
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
In this review we demonstrate how the interplay of genomics, bioinformatics and genomic technologies has enabled an in-depth analysis of the component enzymes of the bacterial fatty-acid biosynthesis pathway as a source of novel antibacterial targets. This evaluation has revealed that many of the enzymes are potentially selective, broad-spectrum antibacterial targets. We also illustrate the suitability of some of these targets for HTS. Furthermore, we discuss how the availability of a robust selectivity assay, mode-of-action assays and numerous crystal structures provide an excellent set of tools with which to initiate integrated programs of research to identify novel antibiotics targeted at these enzymes.
引用
收藏
页码:537 / 544
页数:8
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共 46 条
  • [1] Amber D, 2000, SCIENTIST, V14, P1
  • [2] A mechanism of drug action revealed by structural studies of enoyl reductase
    Baldock, C
    Rafferty, JB
    Sedelnikova, SE
    Baker, PJ
    Stuitje, AR
    Slabas, AR
    Hawkes, TR
    Rice, DW
    [J]. SCIENCE, 1996, 274 (5295) : 2107 - 2110
  • [3] INHA, A GENE ENCODING A TARGET FOR ISONIAZID AND ETHIONAMIDE IN MYCOBACTERIUM-TUBERCULOSIS
    BANERJEE, A
    DUBNAU, E
    QUEMARD, A
    BALASUBRAMANIAN, V
    UM, KS
    WILSON, T
    COLLINS, D
    DELISLE, G
    JACOBS, WR
    [J]. SCIENCE, 1994, 263 (5144) : 227 - 230
  • [4] BERGSMA DJ, 2000, Patent No. 0514301
  • [5] Antibiotic discovery: is it all in the genes?
    Brown, JR
    Warren, PV
    [J]. DRUG DISCOVERY TODAY, 1998, 3 (12) : 564 - 566
  • [6] Animal fatty acid synthase: Functional mapping and cloning and expression of the domain I constituent activities
    Chirala, SS
    Huang, WY
    Jayakumar, A
    Sakai, K
    Wakil, SJ
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (11) : 5588 - 5593
  • [7] CLOUGH RC, 1992, J BIOL CHEM, V267, P20992
  • [8] DEBOUCK C, 1999, Patent No. 9167302
  • [9] GENTRY DR, 1998, Patent No. 98177791
  • [10] GENTRY DR, 1998, Patent No. 98221331