da Silva Fernanda Motta Ribeiro, Paggi Gecele Matos, Brust Flávia Roberta, Macedo Alexandre José, Silva Denise Brentan
Laboratory of Natural Products and Mass Spectrometry (LaPNEM), Federal University of Mato Grosso do Sul, Campo Grande 79070-900, Brazil.
Laboratory of Ecology and Evolutionary Biology (LEBio), Institute of Biosciences, Federal University of Mato Grosso do Sul, Campo Grande 79070-900, Brazil.
Metabolites. 2023 Feb 5;13(2):236. doi: 10.3390/metabo13020236.
Metabolomics strategies are important tools to get holistic chemical information from a system, but they are scarcely applied to endophytic fungi to understand their chemical profiles of biosynthesized metabolites. Here sp. was cultured using One Strain Many Compounds (OSMAC) conditions as a model system to demonstrate how this strategy can help in understanding metabolic profiles and determining bioactive metabolites with the application of metabolomics and statistical analyses, as well as molecular networking. sp. was fermented in different culture media and the crude extracts from mycelial biomass (CEm) and broth (CEb) were obtained, evaluated against bacterial strains ( and ), and the metabolomic profiles by LC-DAD-MS were obtained and chemometrics statistical analyses were applied. The CEm and CEb extracts presented different chemical profiles and antibacterial activities; the highest activities observed were against from CEm (MIC = 16, 64, and 128 µg/mL). The antibacterial properties from the extracts were impacted for culture media from which the strain was fermented. From the Volcano plot analysis, it was possible to determine statistically the most relevant features for the antibacterial activity, which were also confirmed from biplots of PCA as strong features for the bioactive extracts. These compounds included (13-oxoverruculogen isomer), (austalide P acid), (austalide L or W), (helvamide), (viridicatumtoxin A), (austalide P), (dihydroaustalide K), (austalide k), (spirohexaline), and (pre-viridicatumtoxin). Thus, these features included diketopiperazines, meroterpenoids, and polyketides, such as indole alkaloids, austalides, and viridicatumtoxin A, a rare tetracycline.
代谢组学策略是从一个系统中获取整体化学信息的重要工具，但它们很少应用于内生真菌，以了解其生物合成代谢产物的化学特征。在这里，以“一种菌株多种化合物”（OSMAC）条件培养某菌株作为模型系统，以证明该策略如何通过代谢组学、统计分析以及分子网络技术帮助理解代谢谱并确定生物活性代谢产物。将该菌株在不同培养基中发酵，获得菌丝体生物质（CEm）和发酵液（CEb）的粗提物，针对细菌菌株（具体菌株未给出）进行评估，获得LC-DAD-MS的代谢组学谱并应用化学计量学统计分析。CEm和CEb提取物呈现出不同的化学特征和抗菌活性；观察到的最高活性是针对来自CEm的某细菌（具体细菌未给出）（MIC = 16、64和128 µg/mL）。提取物的抗菌特性受到菌株发酵所用培养基的影响。通过火山图分析，可以从统计学上确定抗菌活性最相关的特征，主成分分析双标图也证实这些是生物活性提取物的显著特征。这些化合物包括（13-氧代疣孢菌素异构体）、（奥斯特内酯P酸）、（奥斯特内酯L或W）、（黄绿酰胺）、（绿青霉素毒素A）、（奥斯特内酯P）、（二氢奥斯特内酯K）、（奥斯特内酯k）、（螺己环碱）和（前绿青霉素毒素）。因此，这些特征包括二酮哌嗪、杂萜类化合物和聚酮化合物，如吲哚生物碱、奥斯特内酯和绿青霉素毒素A（一种罕见的四环素）。
