Tools for discovery of inhibitors of the 1-deoxy-D-xylulose 5-phosphate (DXP) synthase and DXP reductoisomerase:: an approach with enzymes from the pathogenic bacterium Pseudomonas aeruginosa

Tools for discovery of inhibitors of the 1-deoxy-D-xylulose 5-phosphate (DXP) synthase and DXP reductoisomerase:: an approach with enzymes from the pathogenic bacterium Pseudomonas aeruginosa
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DOI:
10.1111/j.1574-6968.2000.tb09307.x
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发表时间:
2000-09-15
影响因子:
2.1
通讯作者:
Jomaa, H
Jomaa, H
中科院分区:
生物学4区
文献类型:
--
作者:
Altincicek, B;Hintz, M;Jomaa, H

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铜绿假单胞菌的两个基因编码 1-脱氧-D-木酮糖 5-磷酸 (DXP) 合酶和 DXP 还原异构酶,两者均参与不依赖甲羟戊酸的类异戊二烯生物合成,已在大肠杆菌中表达为重组酶。采用完善的方法,纯化的铜绿假单胞菌 DXP 还原异构酶可被亚微摩尔浓度的抗生素福米霉素和 FR-900098 抑制。开发了一种新颖且方便的分光光度测定法来测定铜绿假单胞菌 DXP 合酶的活性和抑制。氟丙酮酸被描述为 DXP 合酶的第一个抑制剂。 (C) 2000 年欧洲微生物学会联合会。由 Elsevier Science B.V. 出版。保留所有权利。
Two Pseudomonas aeruginosa genes encoding the enzymes 1-deoxy-D-xylulose 5-phosphate (DXP) synthase and DXP reductoisomerase, both involved in the mevalonate-independent biosynthesis of isoprenoids, have been expressed as recombinant enzymes in Escherichia coli. The purified P. aeruginosa DXP reductoisomerase was inhibited by submicromolar concentrations of the antibiotics fosmidomycin and FR-900098 in a well established method. A novel and convenient spectrophotometric assay was developed to determine activity and inhibition of P. aeruginosa DXP synthase. Fluoropyruvate is described as a first inhibitor of DXP synthase. (C) 2000 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved.