In nature, secondary metabolites have been proven to be the essential communication media between co-occurring microorganisms and to influence their relationship with each other. In this study, we conducted a metabolomics survey of the secondary metabolites of an artificial co-culture related to a hydrothermal vent fungal–bacterial community comprising Aspergillus sclerotiorum and Streptomyces and their reciprocal relationship. The fungal strain was found to increase the secretion of notoamides and the compound cyclo(Pro-Trp) produced by the actinomycetes strain was discovered to be the responsible molecule. This led to the hypothesis that the fungi transformed cyclo(Pro-Trp) synthesized by the actinomycetes as the biosynthetic precursors of notoamides in the chemical communication. Further analysis showed Streptomyces sp. WU20 was efficient in transforming amino acids into cyclo(Pro-Trp) and adding tryptophan as well as proline into the chemical communication enhanced the induction of the notoamide accumulation. Thus, we propose that the microbial transformation during the synthetic metabolically-mediated chemical communication might be a promising means of speeding up the discovery of novel bioactive molecules. The objective of this research was to clarify the mechanism of microbial transformation for the chemical communication. Besides, this research also highlights the utility of mass spectrometry-based metabolomics as an effective tool in the direct biochemical analysis of community metabolites.

BackgroundSkin photoaging is primarily driven by mitochondrial dysfunction. Although natural products have demonstrated protective effects against UV-induced damage, efficient screening strategies for mitochondrial-targeting compounds remain limited. AI-assisted high-content screening strategy offers a valuable approach to identify bioactive candidates and elucidate their mechanisms. Purpose This study aimed to employed an AI-assisted high-content screening strategy to identify mitochondrial-enhancing natural compounds that prevent skin photoaging and to evaluate their protective efficacy. MethodsThis study employed an AI-assisted high-content screening strategy to identify mitochondria-targeting compounds that mitigate photodamage. UVB-induced models were established in cells, zebrafish, and mice with UVB lamp irradiation. Mitochondrial morphology and function were quantified using JC-1, TMRM, and MitoTracker probes. Cell viability, SA-β-gal activity, and protein expression were assessed by CCK-8 assay, SA-β-gal staining, and Western blotting, respectively. ResultsAI-assisted high-content screening strategy identified quercetin, spermidine, adenosine, MK-7 and MJE as the potential mitochondrial protective drugs. The optimized combinations CC-1 and CC-2 restored ATP production, increased TCA flux and normalized mitochondrial morphology in UVB-induced HDFs, accompanied by down-regulation of SA-β-gal and up-regulation of COLLAGEN I, LAMIN B1 and SIRT3. In a UVB-exposed zebrafish tail amputation model, CC-2 markedly promoted fin regeneration. These findings were confirmed in UVB-irradiated mice, where CC-2 demonstrated superior efficacy. ConclusionUsing AI-assisted high-content screening, we formulated two optimized combinations that alleviate UVB-induced skin photoaging, with CC-2 exhibiting superior efficacy, highlighting its potential as cosmetic additives.

Four new compounds (1–4), including two new quinazoline-containing indole alkaloids, tryptoquivaline Z₁ (1) and clavutoine V (2); a new cytochalasan alkaloid, cytochalasin Z₂₉ (3); and methyl (S)-2-(2,5-dihydroxyphenyl)-2-methoxyacetate (4), along with one known compound (5), were isolated from culture extracts of the hydrothermal vent crab-derived fungus Aspergillus clavatus C2WU. The structures of the new compounds, including their absolute configurations, were determined by NMR and MS spectroscopic data analyses and comparison between the calculated and experimental ECD spectra. In vitro, compound 2 (clavutoine V) preserves mitochondrial function by reducing the level of mitochondrial membrane potential (MMP) and increasing mitochondrial ATP production. Furthermore, compound 2 might regulate lipid metabolism by reducing ROS. Complementary molecular dynamics simulations support a cardiolipin-associated membrane-modulation mechanism, suggesting that compound 2 may melt rigid lipid domains to restore membrane electrostatic homeostasis. Compounds 1 (tryptoquivaline Z₁), 2 (clavutoine V), and 5 (arthriniumnin A) effectively attenuated UVB-induced mitochondrial dysfunction and ROS overproduction in skin cells, demonstrating their anti-photoaging potential. Additionally, compound 4 (methyl (S)-2-(2,5-dihydroxyphenyl)-2-methoxyacetate) displayed strong ability to scavenge free radicals with an IC₅₀ value of 34.3 μM. It not only reduced UVB-induced ROS production in HaCaT cells but also attenuated glucose-induced AGE formation in HDF cells, further confirming its antioxidant capacity. These findings highlight the potential of hydrothermal vent-derived fungi as a source of bioactive leads for dermatological applications, anti-aging interventions, and mitochondrial medicine.