Biosynthesis of the antifungal haterumalide, oocydin A, in Serratia, and its regulation by quorum sensing, RpoS and Hfq.
Biosynthesis of the antifungal haterumalide, oocydin A, in Serratia, and its regulation by quorum sensing, RpoS and Hfq.
复制标题
塞拉蒂亚中抗真菌性haterumalide，卵母细胞A的生物合成及其对法定感应，RPOS和HFQ的调节。
DOI：
10.1111/1462-2920.12839
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发表时间：
2015-08
影响因子：
5.1
通讯作者：
Salmond GP
中科院分区：
文献类型：
--
作者：
Matilla MA;Leeper FJ;Salmond GP
聚酮化合物是一类重要的具有广泛生物活性的天然产物。我们最近发现了一个大的反式酰基转移酶（AT）聚酮合酶基因簇负责的抗真菌，抗卵菌和抗肿瘤haterumalide，卵胞素A（ooc）的生物合成。利用基因组测序和比较基因组学，我们表明，ooc基因簇是广泛的生物控制和植物病原菌株的肠杆菌，沙雷氏菌和Dickeya。框内缺失突变体的分析证实了一个羟甲基戊二酰辅酶A合酶盒，三个黄素依赖的剪裁酶，一个独立的酰基载体蛋白和两个假设的蛋白质在卵环素A的生物合成中的作用。还证明了大环内酯生物合成所需的三个反式作用AT结构域。ooc基因簇的表达被证明是正调控的N-酰基-L-高丝氨酸内酯为基础的群体感应系统，但在应变依赖性的方式操作。在转录后水平，RNA伴侣Hfq在卵胞素A的生物合成中起关键作用。Hfq依赖性调节部分由固定相sigma因子RpoS介导，RpoS也显示出正调节大环内酯的合成。我们的研究结果揭示了差异调节的分歧转录卵母细胞的转录单位，突出了卵胞素A生产的复杂性。
Polyketides represent an important class of bioactive natural products with a broad range of biological activities. We identified recently a large trans-acyltransferase (AT) polyketide synthase gene cluster responsible for the biosynthesis of the antifungal, anti-oomycete and antitumor haterumalide, oocydin A (ooc). Using genome sequencing and comparative genomics, we show that the ooc gene cluster is widespread within biocontrol and phytopathogenic strains of the enterobacteria, Serratia and Dickeya. The analysis of in frame deletion mutants confirmed the role of a hydroxymethylglutaryl-coenzyme A synthase cassette, three flavin-dependent tailoring enzymes, a free-standing acyl carrier protein and two hypothetical proteins in oocydin A biosynthesis. The requirement of the three trans-acting AT domains for the biosynthesis of the macrolide was also demonstrated. Expression of the ooc gene cluster was shown to be positively regulated by an N-acyl-L-homoserine lactone-based quorum sensing system, but operating in a strain-dependent manner. At a post-transcriptional level, the RNA chaperone, Hfq, plays a key role in oocydin A biosynthesis. The Hfq-dependent regulation is partially mediated by the stationary phase sigma factor, RpoS, which was also shown to positively regulate the synthesis of the macrolide. Our results reveal differential regulation of the divergently transcribed ooc transcriptional units, highlighting the complexity of oocydin A production.