Microbial biotransformation of Syzygium australe modifies metabolomic profile assessed with multivariate analysis and...

Syzygium australe, a comparatively less studied species within the Syzygium genus, is emerging as a prospective source of bioactive phytochemicals. In this study, the impact of microbial biotransformation by Aspergillus niger on the metabolomic and bioactivity profiles of S. australe leaves extract (SAE) was evaluated. UPLC-T-TOF-MS/MS and molecular networking enabled the tentative identification of 80 metabolites in SAE, with flavonoids emerging as the dominant phytoconstituents. After biotransformation, sulfated flavonoids are the main metabolites in S. australe biotransformed extract (SABE), suggesting that enzymatic sulfonation is mediated by fungal sulfotransferase enzymes. Molecular networking revealed two key clusters: cluster A, which is primarily composed of quercetin derivatives, and cluster B, which corresponded to syringetin. Notably, the biotransformed metabolites in SABE were predominantly observed as self-looped nodes, indicating the formation of structurally unique compounds. Multivariate chemometric analyses revealed a significant metabolomic modulation and a clear discrimination between SAE and SABE. Compared with SABE, SAE significantly increased the free radical scavenging capacity, as evidenced by lower IC₅₀ values in DPPH and ABTS assays (36.96 ± 1.20 and 19.80 ± 0.85 µg/mL respectively), which is likely a consequence of tannin degradation during microbial biotransformation. The bioactivity of SABE, particularly against pancreatic lipase, was enhanced, with an inhibition rate of 74.49 ± 4.80% at 100 µg/mL. Molecular docking further supported these findings, highlighting isorhamnetin-3-O-sulfate as a key bioactive constituent with the highest binding affinity to pancreatic lipase (ΔG = - 12.47 kcal/mol). These findings highlight a significant potential and warrant further investigation using alternative microbial strains aiming to develop novel therapeutic agents.