Fimbrolide Natural Products Disrupt Bioluminescence of Vibrio By Targeting Autoinducer Biosynthesis and Luciferase Activity.
Fimbrolide Natural Products Disrupt Bioluminescence of Vibrio By Targeting Autoinducer Biosynthesis and Luciferase Activity.
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DOI：
10.1002/anie.201508052
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发表时间：
2016-01
影响因子：
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通讯作者：
Weining Zhao;N. Lorenz;K. Jung;S. Sieber
中科院分区：
文献类型：
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作者：
Weining Zhao;N. Lorenz;K. Jung;S. Sieber
弧菌是群体感应（quorum sensing， QS）信号研究的模式生物，被用来识别干扰QS的药物。天然存在的薄膜化合物是已知影响各种生物QS的重要工具化合物；然而，到目前为止，它们的细胞目标仍然难以捉摸。在此，我们利用定制探针，通过定量质谱技术鉴定了活体V. harveyi和V. campbelllii蛋白质组中不可逆的膜苷靶标。其中主要打击的是在弧菌QS和生物发光中起重要作用的两个蛋白质靶点。LuxS负责自诱导剂2的生物合成，LuxE是荧光素酶复合物的一个亚基，它们的活性位点半胱氨酸都被共价修饰，导致活性抑制。LuxE的鉴定统一了先前关于信号级联下游生物发光抑制的报道，从而有助于更好地理解这些QS工具化合物的机制。
Vibrio is a model organism for the study of quorum sensing (QS) signaling and is used to identify QS-interfering drugs. Naturally occurring fimbrolides are important tool compounds known to affect QS in various organisms; however, their cellular targets have so far remained elusive. Here we identify the irreversible fimbrolide targets in the proteome of living V. harveyi and V. campbellii via quantitative mass spectrometry utilizing customized probes. Among the major hits are two protein targets with essential roles in Vibrio QS and bioluminescence. LuxS, responsible for autoinducer 2 biosynthesis, and LuxE, a subunit of the luciferase complex, were both covalently modified at their active-site cysteines leading to inhibition of activity. The identification of LuxE unifies previous reports suggesting inhibition of bioluminescence downstream of the signaling cascade and thus contributes to a better mechanistic understanding of these QS tool compounds.