Sequeira Patrícia, Rothkegel Maika, Domingos Patrícia, Martins Isabel, Leclercq Céline C, Renaut Jenny, Goldman Gustavo H, Silva Pereira Cristina
Applied and Environmental Mycology Laboratory, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa (ITQB-NOVA), Oeiras, Portugal.
Integrative Biology Platform, Environmental Research and Technology Platform, Luxembourg Institute of Science and Technology, Belvaux, Luxembourg.
Front Microbiol. 2022 Jul 25;13:946286. doi: 10.3389/fmicb.2022.946286. eCollection 2022.
Fungal secondary metabolites constitute a rich source of yet undiscovered bioactive compounds. Their production is often silent under standard laboratory conditions, but the production of some compounds can be triggered simply by altering the cultivation conditions. The usage of an organic salt - ionic liquid - as growth medium supplement can greatly impact the biosynthesis of secondary metabolites, leading to higher diversity of compounds accumulating extracellularly. This study examines if such supplements, specifically cholinium-based ionic liquids, can support the discovery of bioactive secondary metabolites across three model species: , and . Enriched organic extracts obtained from medium supernatant revealed high diversity in metabolites. The supplementation led apparently to increased levels of either 1-aminocyclopropane-1-carboxylate or α-aminoisobutyric acid. The extracts where bioactive against two major foodborne bacterial strains: and . In particular, those retrieved from cultures showed greater bactericidal potential compared to control extracts derived from non-supplemented cultures. An untargeted mass spectrometry analysis using the Global Natural Product Social Molecular Networking tool enabled to capture the chemical diversity driven by the ionic liquid stimuli. Diverse macrolides, among other compounds, were putatively associated with ; whereas an unexpected richness of cyclic (depsi)peptides with . Further studies are required to understand if the identified peptides are the major players of the bioactivity of extracts, and to decode their biosynthesis pathways as well.
真菌次级代谢产物构成了尚未被发现的生物活性化合物的丰富来源。在标准实验室条件下，它们的产生往往是不明显的，但某些化合物的产生可以通过改变培养条件来简单地触发。使用有机盐——离子液体——作为生长培养基补充剂，可极大地影响次级代谢产物的生物合成，导致细胞外积累的化合物具有更高的多样性。本研究考察了此类补充剂，特别是基于胆碱的离子液体，是否能支持在三种模式物种：[此处原文缺失物种名称]、[此处原文缺失物种名称]和[此处原文缺失物种名称]中发现生物活性次级代谢产物。从培养基上清液中获得的富集有机提取物显示出代谢产物的高度多样性。这种补充显然导致1-氨基环丙烷-1-羧酸或α-氨基异丁酸水平升高。这些提取物对两种主要的食源细菌菌株：[此处原文缺失细菌菌株名称]和[此处原文缺失细菌菌株名称]具有生物活性。特别是，与未补充培养物的对照提取物相比，从[此处原文缺失物种名称]培养物中获得的提取物显示出更大的杀菌潜力。使用全球天然产物社会分子网络工具进行的非靶向质谱分析能够捕捉由离子液体刺激驱动的化学多样性。除其他化合物外，多种大环内酯类化合物被推测与[此处原文缺失物种名称]有关；而[此处原文缺失物种名称]则有意外丰富的环状（缩酚）肽。还需要进一步研究，以了解所鉴定的肽是否是[此处原文缺失物种名称]提取物生物活性的主要参与者，并解码它们的生物合成途径。
