Natural Product Proteomining, a Quantitative Proteomics Platform, Allows Rapid Discovery of Biosynthetic Gene Clusters for Different Classes of Natural Products
Natural Product Proteomining, a Quantitative Proteomics Platform, Allows Rapid Discovery of Biosynthetic Gene Clusters for Different Classes of Natural Products
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DOI：
10.1016/j.chembiol.2014.03.011
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发表时间：
2014-06-19
影响因子：
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通讯作者：
van Wezel, Gilles P.
中科院分区：
文献类型：
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作者：
Gubbens, Jacob;Zhu, Hua;van Wezel, Gilles P.
由于目前可用的基因组测序数据的激增，有关天然产物生物合成的基因簇的信息正在迅速积累。然而，将天然产物与特定基因簇联系起来仍然具有挑战性。在这里，我们提出了一种广泛适用的策略，用于鉴定特定天然产物的基因簇，我们将其命名为天然产物蛋白质形成。该方法基于使用波动生长条件，以确保感兴趣的生物活性的差异生物合成。随后，代谢组学和定量蛋白质组学的结合建立了天然产物丰度与蛋白质池中伴随变化之间的相关性，从而可以识别相关的生物合成基因簇。我们使用这种方法来阐明芽孢杆菌和链霉菌中不同天然产物的基因簇，包括一种新的巨霉素型抗生素。天然产物蛋白质组学不需要事先了解基因簇或次级代谢物，因此代表了识别所有类型基因簇的一般策略。
Information on gene clusters for natural product biosynthesis is accumulating rapidly because of the current boom of available genome sequencing data. However, linking a natural product to a specific gene cluster remains challenging. Here, we present a widely applicable strategy for the identification of gene clusters for specific natural products, which we name natural product proteomining. The method is based on using fluctuating growth conditions that ensure differential biosynthesis of the bioactivity of interest. Subsequent combination of metabolomics and quantitative proteomics establishes correlations between abundance of natural products and concomitant changes in the protein pool, which allows identification of the relevant biosynthetic gene cluster. We used this approach to elucidate gene clusters for different natural products in Bacillus and Streptomyces, including a novel juglomycin-type antibiotic. Natural product proteomining does not require prior knowledge of the gene cluster or secondary metabolite and therefore represents a general strategy for identification of all types of gene clusters.