Department of Plant Pathology, Washington State University, Pullman, Washington, USA.
Korean Lichen Research Institute, Sunchon National University, Suncheon, Jeonnam, South Korea.
mSphere. 2019 Sep 25;4(5):e00622-19. doi: 10.1128/mSphere.00622-19.
The polyketide-derived secondary metabolite ascochitine is produced by species in the Didymellaceae family, including but not restricted to species pathogens of cool-season food legumes. Ascochitine is structurally similar to the well-known mycotoxin citrinin and exhibits broad-spectrum phytotoxicity and antimicrobial activities. Here, we identified a polyketide synthase (PKS) gene (denoted ) responsible for ascochitine production in the filamentous fungus Deletion of the prevented production of ascochitine and its derivative ascochital in The putative ascochitine biosynthesis gene cluster comprises 11 genes that have undergone rearrangement and gain-and-loss events relative to the citrinin biosynthesis gene cluster in Interestingly, we also identified homologs in two recently diverged species, and var. , that are sister taxa closely related to ascochitine producers such as and However, nonsense mutations have been independently introduced in coding sequences of the homologs of and var. that resulted in loss of ascochitine production. Despite its reported phytotoxicity, ascochitine was not a pathogenicity factor in infection and colonization of faba bean ( L.). Ascochitine was mainly produced from mature hyphae at the site of pycnidial formation, suggesting a possible protective role of the compound against other microbial competitors in nature. This report highlights the evolution of gene clusters harnessing the structural diversity of polyketides and a mechanism with the potential to alter secondary metabolite profiles via single nucleotide polymorphisms in closely related fungal species. Fungi produce a diverse array of secondary metabolites, many of which are of pharmacological importance whereas many others are noted for mycotoxins, such as aflatoxin and citrinin, that can threaten human and animal health. The polyketide-derived compound ascochitine, which is structurally similar to citrinin mycotoxin, has been considered to be important for pathogenicity of legume-associated species. Here, we identified the ascochitine polyketide synthase (PKS) gene in and its neighboring genes that may be involved in ascochitine biosynthesis. Interestingly, the ascochitine PKS genes in other legume-associated species have been mutated, encoding truncated PKSs. This indicated that point mutations may have contributed to genetic diversity for secondary metabolite production in these fungi. We also demonstrated that ascochitine is not a pathogenicity factor in The antifungal activities and production of ascochitine during sporulation suggested that it may play a role in competition with other saprobic fungi in nature.
多酮衍生的次生代谢物麦角硫因由 Didymellaceae 科的物种产生，包括但不限于冷季食用豆科植物的病原菌。麦角硫因的结构与著名的真菌毒素桔青霉素相似，具有广谱的植物毒性和抗菌活性。在这里，我们鉴定了一个多酮合酶（PKS）基因（表示为 ），该基因负责丝状真菌 中麦角硫因的产生。该基因的缺失阻止了麦角硫因及其衍生物麦角硫因在 中的产生。推测的麦角硫因生物合成基因簇包含 11 个基因，相对于桔青霉素生物合成基因簇在 中经历了重排和获得-丢失事件。有趣的是，我们还在两个最近分化的物种 和 var. 中鉴定到了 的同源物，它们是与麦角硫因生产者如 和 密切相关的姐妹分类群。然而，在 和 var. 的 同源物的编码序列中已经独立引入了无意义突变，导致麦角硫因的产生丧失。尽管麦角硫因具有报道的植物毒性，但它不是 在羽扁豆（ ）中的侵染和定植的致病性因素。麦角硫因主要由产孢部位成熟菌丝产生，这表明该化合物可能在自然中对其他微生物竞争者具有保护作用。本报告强调了利用多酮结构多样性的基因簇的进化，以及通过密切相关真菌物种中的单核苷酸多态性改变次生代谢物谱的潜在机制。真菌产生多种结构多样的次生代谢物，其中许多具有药理学重要性，而许多其他次生代谢物则以真菌毒素（如黄曲霉毒素和桔青霉素）为特征，这些毒素可能威胁人类和动物的健康。多酮衍生的化合物麦角硫因，其结构与桔青霉素真菌毒素相似，被认为对豆科植物相关 物种的致病性很重要。在这里，我们鉴定了 中的麦角硫因聚酮合酶（PKS）基因及其可能参与麦角硫因生物合成的邻近基因。有趣的是，其他与豆科植物相关的 物种中的麦角硫因 PKS 基因已经发生了突变，编码截短的 PKSs。这表明点突变可能导致这些真菌中次生代谢物产生的遗传多样性。我们还证明了麦角硫因不是 在 中的致病性因素。在孢子形成过程中抗真菌活性和麦角硫因的产生表明，它可能在与自然中其他腐生真菌的竞争中发挥作用。
