Bacteria-induced natural product formation in the fungus Aspergillus nidulans requires Saga/Ada-mediated histone acetylation
Bacteria-induced natural product formation in the fungus Aspergillus nidulans requires Saga/Ada-mediated histone acetylation
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DOI：
10.1073/pnas.1103523108
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发表时间：
2011-08-23
影响因子：
11.1
通讯作者：
Brakhage, Axel A.
中科院分区：
文献类型：
--
作者：
Nuetzmann, Hans-Wilhelm;Reyes-Dominguez, Yazmid;Brakhage, Axel A.
真菌基因组的序列分析表明，真菌产生次级代谢产物的潜力被大大低估。事实上，大多数编码抗生素、毒素或色素生物合成的基因簇在标准实验室条件下是沉默的。因此，揭示途径激活所需的机制是微生物学的主要挑战之一。最近，我们发现，密切的物理相互作用的重要模式真菌构巢曲霉与土壤中的细菌雷帕霉素链霉菌特异性激活沉默的真菌次生代谢基因，导致原型的聚酮苔草酸及其衍生物的生产。在这里，我们报告说，链霉菌触发修改真菌组蛋白。对40种乙酰转移酶中的36种进行了缺失分析，包括A. nidulans，证明了含有HAT GcnE和AdaB蛋白的佐贺/Ada复合物是细菌诱导地衣酸基因簇所必需的。我们还发现，佐贺/Ada在其他生物合成基因簇的特异性诱导中起着重要作用，如杂色曲霉素、terquinone和青霉素。染色质免疫沉淀结果表明，在真菌和细菌的相互作用过程中，组蛋白3的第9和第14位赖氨酸乙酰化水平发生了佐贺/Ada依赖性的升高。此外，还研究了A. nidulans的增加伴随着H3 K14乙酰化的整体增加。然而，增加的H3 K9乙酰化仅在基因簇内发现。本报告提供了以前未描述的证据佐贺/Ada依赖组蛋白乙酰化引发的原核生物。
Sequence analyses of fungal genomes have revealed that the potential of fungi to produce secondary metabolites is greatly underestimated. In fact, most gene clusters coding for the biosynthesis of antibiotics, toxins, or pigments are silent under standard laboratory conditions. Hence, it is one of the major challenges in microbiology to uncover the mechanisms required for pathway activation. Recently, we discovered that intimate physical interaction of the important model fungus Aspergillus nidulans with the soil-dwelling bacterium Streptomyces rapamycinicus specifically activated silent fungal secondary metabolism genes, resulting in the production of the archetypal polyketide orsellinic acid and its derivatives. Here, we report that the streptomycete triggers modification of fungal histones. Deletion analysis of 36 of 40 acetyltransferases, including histone acetyltransferases (HATs) of A. nidulans, demonstrated that the Saga/Ada complex containing the HAT GcnE and the AdaB protein is required for induction of the orsellinic acid gene cluster by the bacterium. We also showed that Saga/Ada plays a major role for specific induction of other biosynthesis gene clusters, such as sterigmatocystin, terrequinone, and penicillin. Chromatin immunoprecipitation showed that the Saga/Ada-dependent increase of histone 3 acetylation at lysine 9 and 14 occurs during interaction of fungus and bacterium. Furthermore, the production of secondary metabolites in A. nidulans is accompanied by a global increase in H3K14 acetylation. Increased H3K9 acetylation, however, was only found within gene clusters. This report provides previously undescribed evidence of Saga/Ada dependent histone acetylation triggered by prokaryotes.