Intimate bacterial-fungal interaction triggers biosynthesis of archetypal polyketides in Aspergillus nidulans
Intimate bacterial-fungal interaction triggers biosynthesis of archetypal polyketides in Aspergillus nidulans
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DOI：
10.1073/pnas.0901870106
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发表时间：
2009-08-25
影响因子：
11.1
通讯作者：
Brakhage, Axel A.
中科院分区：
文献类型：
--
作者：
Schroeckh, Volker;Scherlach, Kirstin;Brakhage, Axel A.
真菌产生许多具有多种生物活性的低分子量分子。然而，挖掘真菌的全基因组序列表明，它们产生次级代谢产物的潜力被大大低估了。由于大多数生物合成基因簇在实验室条件下是沉默的，因此主要挑战之一是了解这些基因被激活的生理条件。因此，我们共培养的重要模式真菌构巢曲霉与收集的58土壤放线菌。通过对曲霉次级代谢基因和全基因组芯片的微阵列分析以及北方印迹和定量RT-PCR分析，我们在分子水平上证明了一种独特的真菌-细菌相互作用导致真菌次级代谢基因的特异性激活。最令人惊讶的是，透析实验和电子显微镜表明，一个亲密的物理相互作用的细菌和真菌菌丝体引起的具体反应。基因敲除实验提供的证据表明，一个诱导的基因簇编码的聚酮合酶（PKS）的生物合成所需的原型聚酮地衣酸，典型的地衣代谢产物lecanoric酸，和组织蛋白酶K抑制剂F-9775 A和F-9775 B的长期追求。系统发育分析表明，该PKS的直系同源物在自然界中广泛存在于所有主要的真菌群中，包括地衣的真菌。这些结果提供了属于不同领域的微生物之间的特定相互作用的证据，并支持这一假设，不仅扩散信号，但亲密的物理相互作用有助于微生物之间的通信和诱导，否则沉默的生物合成基因。
Fungi produce numerous low molecular weight molecules endowed with a multitude of biological activities. However, mining the full-genome sequences of fungi indicates that their potential to produce secondary metabolites is greatly underestimated. Because most of the biosynthesis gene clusters are silent under laboratory conditions, one of the major challenges is to understand the physiological conditions under which these genes are activated. Thus, we cocultivated the important model fungus Aspergillus nidulans with a collection of 58 soil-dwelling actinomycetes. By microarray analyses of both Aspergillus secondary metabolism and full-genome arrays and Northern blot and quantitative RT-PCR analyses, we demonstrate at the molecular level that a distinct fungal-bacterial interaction leads to the specific activation of fungal secondary metabolism genes. Most surprisingly, dialysis experiments and electron microscopy indicated that an intimate physical interaction of the bacterial and fungal mycelia is required to elicit the specific response. Gene knockout experiments provided evidence that one induced gene cluster codes for the long-sought after polyketide synthase (PKS) required for the biosynthesis of the archetypal polyketide orsellinic acid, the typical lichen metabolite lecanoric acid, and the cathepsin K inhibitors F-9775A and F-9775B. A phylogenetic analysis demonstrates that orthologs of this PKS are widespread in nature in all major fungal groups, including mycobionts of lichens. These results provide evidence of specific interaction among microorganisms belonging to different domains and support the hypothesis that not only diffusible signals but intimate physical interactions contribute to the communication among microorganisms and induction of otherwise silent biosynthesis genes.