Texas Therapeutic Institute, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77054, USA.
Institute for Applied Cancer Science, M.D. Anderson Cancer Center, Houston, TX 77054, USA.
Molecules. 2020 Feb 18;25(4):913. doi: 10.3390/molecules25040913.
is an industrially important fungus for the production of the antifungal echinocandin B and is closely related to model organism . Its secondary metabolism is largely unknown except for the production of echinocandin B and sterigmatocystin. We constructed mutants for three genes that regulate secondary metabolism in NRRL 11440, and evaluated the secondary metabolites produced by wild type and mutants strains. The secondary metabolism was explored by metabolic networking of UPLC-HRMS/MS data. The genes and metabolites of were compared to those of FGSC A4 as a reference to identify compounds and link them to their encoding genes. Major differences in chromatographic profiles were observable among the mutants. At least 28 molecules were identified in crude extracts that corresponded to nine characterized gene clusters. Moreover, metabolic networking revealed the presence of a yet unexplored array of secondary metabolites, including several undescribed fellutamides derivatives. Comparative reference to its sister species, , was an efficient way to dereplicate known compounds, whereas metabolic networking provided information that allowed prioritization of unknown compounds for further metabolic exploration. The mutation of global regulator genes proved to be a useful tool for expanding the expression of metabolic diversity in .
是一种具有重要工业价值的真菌，可用于生产抗真菌的棘白菌素 B，与模式生物关系密切。除了生产棘白菌素 B 和桔青霉素外，其次级代谢产物在很大程度上尚不清楚。我们构建了调控 NRRL 11440 中次级代谢的三个基因的突变体，并评估了野生型和突变菌株产生的次级代谢产物。通过 UPLC-HRMS/MS 数据的代谢网络分析探索了次级代谢。将 的基因和代谢物与 FGSC A4 的基因和代谢物进行比较，作为鉴定化合物并将其与编码基因联系起来的参考。突变体之间的色谱图谱存在明显差异。在粗提物中鉴定出至少 28 种分子，对应于九个特征基因簇。此外，代谢网络分析揭示了存在一组尚未探索的次级代谢产物，包括几种未描述的 fellutamide 衍生物。与姐妹种 进行比较是一种有效的方法，可以对已知化合物进行去重复，而代谢网络分析提供的信息可以优先考虑对未知化合物进行进一步的代谢探索。全局调控基因的突变被证明是扩展 的代谢多样性的有用工具。
