Top-down mass spectrometry on low-resolution instruments: Characterization of phosphopantetheinylated carrier domains in polyketide and non-ribosomal biosynthetic pathways

被引:58
|
作者
Meluzzi, Dario [3 ]
Zheng, Wei Hao [3 ]
Hensler, Mary [2 ]
Nizet, Victor [1 ,4 ]
Dorrestein, Pieter C. [1 ,2 ,3 ]
机构
[1] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA
[3] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA
[4] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA
关键词
D O I
10.1016/j.bmcl.2007.10.104
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Mass spectrometry (MS) is an important tool for studying non-ribosomal peptide, polyketide, and fatty acid biosynthesis. Here we describe a new approach using multi-stage tandem MS on a common ion trap instrument to obtain high-resolution measurements of the masses of substrates and intermediates bound to phosphopantetheinylated ( holo) carrier proteins. In particular, we report the chemical formulas of 12 diagnostic MS(3) fragments of the phosphopantetheine moiety ejected from holo carrier proteins during MS(2). We demonstrate our method by observing the formation of holo-AcpC, a putative acyl carrier protein from Streptococcus agalactiae. Published by Elsevier Ltd.
引用
收藏
页码:3107 / 3111
页数:5
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