Institute of Microbial Genetics, Department of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences, Vienna, Konrad-Lorenz Strasse 24, 3430, Tulln an der Donau, Austria.
Institute of Bioanalytics and Agro-Metabolomics, Department of Agrobiotechnology (IFA-Tulln), University of Natural Resources and Life Sciences, Vienna, Konrad-Lorenz Strasse 20, 3430, Tulln an der Donau, Austria.
Chembiochem. 2023 Mar 14;24(6):e202200342. doi: 10.1002/cbic.202200342. Epub 2022 Oct 18.
Fusarium mangiferae causes the mango malformation disease (MMD) on young mango trees and seedlings resulting in economically significant crop losses. In addition, F. mangiferae produces a vast array of secondary metabolites (SMs), including mycotoxins that may contaminate the harvest. Their production is tightly regulated at the transcriptional level. Here, we show that lack of the H3 K9-specific histone methyltransferase, FmKmt1, influences the expression of the F. mangiferae polyketide synthase (PKS) 8 (FmPKS8), a so far cryptic PKS. By a combination of reverse genetics, untargeted metabolomics, bioinformatics and chemical analyses including structural elucidation, we determined the FmPKS8 biosynthetic gene cluster (BGC) and linked its activity to the production of fusamarins (FMN), which can be structurally classified as dihydroisocoumarins. Functional characterization of the four FMN cluster genes shed light on the biosynthetic pathway. Cytotoxicity assays revealed moderate toxicities with IC values between 1 and 50 μM depending on the compound.
尖孢镰刀菌引起的芒果畸形病（MMD）会影响幼龄芒果树和幼苗，导致严重的经济损失。此外，尖孢镰刀菌还会产生大量的次生代谢产物（SMs），包括可能污染作物的真菌毒素。它们的产生在转录水平受到严格调控。在这里，我们发现缺乏 H3K9 特异性组蛋白甲基转移酶 FmKmt1 会影响尖孢镰刀菌聚酮合酶 8（FmPKS8）的表达，FmPKS8 是一个迄今为止隐藏的聚酮合酶。通过反向遗传学、非靶向代谢组学、生物信息学和包括结构阐明在内的化学分析的结合，我们确定了 FmPKS8 的生物合成基因簇（BGC），并将其活性与 fusamarins（FMN）的产生联系起来，FMN 可以结构上分类为二氢异香豆素。四个 FMN 簇基因的功能表征揭示了生物合成途径。细胞毒性测定显示，根据化合物的不同，其 IC 值在 1 到 50 μM 之间具有中等毒性。
