Pantethine Rescues Phosphopantothenoylcysteine Synthetase and Phosphopantothenoylcysteine Decarboxylase Deficiency in Escherichia coli but Not in Pseudomonas aeruginosa
Pantethine Rescues Phosphopantothenoylcysteine Synthetase and Phosphopantothenoylcysteine Decarboxylase Deficiency in Escherichia coli but Not in Pseudomonas aeruginosa
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DOI：
10.1128/jb.00334-11
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发表时间：
2011-07-01
影响因子：
3.2
通讯作者：
Tao, Jianshi
中科院分区：
文献类型：
--
作者：
Balibar, Carl J.;Hollis-Symynkywicz, Micah F.;Tao, Jianshi
辅酶A（CoA）在所有生物体中起着核心和重要的作用。辅酶A生物合成途径被认为是开发具有新作用机制的新型抗菌剂的一个有吸引力的靶点。通过使用阿拉伯糖调节的表达系统，在大肠杆菌中证实了coaBC的必要性，coaBC是编码双功能蛋白的单个基因，催化CoA途径中的两个连续步骤，将4 '-磷酸泛酰巯基乙胺转化为4'-磷酸泛酰巯基乙胺。利用该coaBC菌株，进一步证明了E.大肠杆菌可以有效地代谢泛硫乙胺以绕过对coaBC的需要。有趣的是，泛硫乙胺不能被铜绿假单胞菌用于抑制coaBC。通过相互互补研究结合生化特性，证明这两种微生物中泛硫乙胺利用的差异特征是由于与内源性泛酸激酶相关的不同底物特异性，该内源性泛酸激酶是大肠杆菌中coaA编码的CoA生物合成途径中的第一个酶。coli和coaX。
Coenzyme A (CoA) plays a central and essential role in all living organisms. The pathway leading to CoA biosynthesis has been considered an attractive target for developing new antimicrobial agents with novel mechanisms of action. By using an arabinose-regulated expression system, the essentiality of coaBC, a single gene encoding a bifunctional protein catalyzing two consecutive steps in the CoA pathway converting 4'-phosphopantothenate to 4'-phosphopantetheine, was confirmed in Escherichia coli. Utilizing this regulated coaBC strain, it was further demonstrated that E. coli can effectively metabolize pantethine to bypass the requirement for coaBC. Interestingly, pantethine cannot be used by Pseudomonas aeruginosa to obviate coaBC. Through reciprocal complementation studies in combination with biochemical characterization, it was demonstrated that the differential characteristics of pantethine utilization in these two microorganisms are due to the different substrate specificities associated with endogenous pantothenate kinase, the first enzyme in the CoA biosynthetic pathway encoded by coaA in E. coli and coaX in P. aeruginosa.