Microscopic fungi occupy a vast number of habitats, are taxonomically diverse, degrade complex substrates, and have stood out for their capacity to biosynthesize a plethora of specialized metabolites. Such molecules are structurally diverse, and many have applications in fundamental and applied sciences, for example, in medicine, material sciences, food chemistry, textile and pharmaceutical industries, and agronomy, among other fields. However, despite the tremendous biotechnological value of fungi, these organisms are understudied, limiting the knowledge to their taxonomy, chemistry, and some putative applications. Notably, some specific habitats remain unexplored in terms of their mycobiota. Based on these considerations, this review describes the known fungal diversity associated with ants/nests, their metabolic potential, and the possible applications of their specialized metabolites in drug discovery programs focused on developing treatments for human diseases. According to this revision, fungal diversity has been studied by applying conventional methodologies such as isolation and morphological identification of soil fungi from mounds and nest chambers, and indirectly from ants’ cuticles and glands. The subfamilies, genera, taxonomical information, and geographical origin of ants from which filamentous fungi and yeast are commonly isolated are also described. Furthermore, some important information is presented concerning the difference between the ant-associated mycobiota and that in the surroundings, discarding the extrapolation of the chemical and biological information known for soil fungi. Altogether, this review evidenced the lack of information regarding the chemical composition of ant-associated fungi, encouraging research focused on exploring the chemistry biosynthesized from ants’ mycobiota, as well as the elucidation of their allelopathic potential inside the nests. Graphical Abstract

Bioassay-guided fractionation of an active crude extract (EtOAc) of polyfollicles of Magnolia vovidessi, an endemic medicinal plant of the cloud forest of Mexico, led to the isolation and identification of shizukolidol (1), an eudesmane-type sesquiterpenoid lactone that showed antibacterial activity against the economically important phytopathogenic bacterium Chryseobacterium sp. (MIC= 400 μg/mL). In addition, 4α,8β-dihydroxy-5α(H)-eudesm-7(11)-en-8,12-olide 8 (2), rutin, scopoline and scopoletine were also isolated as were mexicanin, parthenolide, costunolide, astragalin, quercetin, hesperidin, p-coumaric acid, chlorogenic acid, vanillin, vanillic acid, 4-hydroxybenzoic acid, protocatechuic acid and shikimic acid identified by a dereplication-like procedure using LC-ESI-MS/MS. Rutin displayed mild anti-oomicite activity against phytopathogen Phytophthora cinnamomi.

Introduction: Antimicrobial resistance is a global public health problem that requires the development of new bioactive compounds. In this context, metabolomic analyses can expedite the research of fungal metabolites as a valuable resource.Objectives: To investigate the metabolic profiles and isolate antibacterial compounds from micromycetes associated with Mexican cloud forest ants by utilizing network analysis of their chemical and bioactivity data.Material and Methods: 248 fungal strains isolated from six ant's species, soil of their anthills, and soil of the surroundings were evaluated for their in vitro inhibition growth of extensively drug‐resistant Acinetobacter baumannii and hypervirulent Klebsiella pneumoniae; subsequently, their metabolites were dereplicated and analyzed by molecular networking and compound activity mapping from spectrometric data. Prioritization of some fungi for isolation of their major constituents was performed, and their structures were established by spectroscopic and spectrometric analysis and their bioactivity determined.Results: From the fungal collection, 15 secondary metabolites (1–15) were dereplicated, and 10 compounds (16–25), including the new (E)‐tridec‐7‐ene‐3,5,6,10‐tetraol (25), were isolated from Ascomycetes of Trichoderma, Cladosporium, and Clonostachys genera. Compounds 16–18 stood out for being bioactive. This study is the first report of antibacterial activity against A. baumannii for the tricyclic pyridin‐2‐ones deoxy‐PF1140 (16) and PF1140 (17), with minimum inhibitory concentration of 50 μg/mL.Conclusion: Network analysis and dereplication proved effective in bioprospecting for antibacterial compounds, offering valuable insights into the chemical diversity of cloud forest soil fungi and their potential applications. Moreover, this study broadens the knowledge of fungal secondary metabolites linked to leafcutter, fire, and warrior ants.

Two new oxygenated solanapyrone analogues, nigrosporapyrone E ( 1 ) and nigrosporapyrone F ( 2 ), were isolated from Nigrospora sp. strain IQ‐064, a fungus associated with the bark of black mangrove ( Avicennia germinans L.), along with seven known compounds. A targeted metabolomic strategy, on the basis of molecular networking and chemotaxonomic criteria, facilitated the isolation of these compounds. Their structures were characterized using HRESIMS and NMR spectroscopic analysis, whereas their relative configurations were established through NOE correlations. The absolute configuration of the new natural products was determined by comparison of experimental and calculated electronic circular dichroism (ECD) spectra, showing consistency with the recently reported natural product sphasolanapyrone A. Considering previous bioprospecting studies of this fungal strain, the isolated compounds were evaluated for their ability to inhibit human protein tyrosine phosphatase 1B ( h PTP1B _1–400 ), a validated target for developing anti‐diabetic drugs, as well as for their inhibitory activity against the pathogen Acinetobacter baumannii clinical isolate A564. However, no significant activity was observed in either bioassay. In addition, their ADME properties and probable bioactivity spectrum, predicted through SwissADME and PASS analysis, respectively, were analyzed to investigate alternative molecular targets within this compound family.