Structural characterization, derivatization, and bioactivities of secondary metabolites produced by termite-associated BYF-106.

Two new C-glycoside angucycline-related analogs, urdamycin Y () and grincamycin W (), as well as eight known metabolites (), were identified from termite-associated BYF-106 based on global natural products social molecular networking (GNPS). The putative biosynthetic pathways of urdamycin Y () and grincamycin W () were proposed using bioinformatic analysis of the full genome of BYF-106. In addition, four new derivative compounds (, , and ) were synthesized via acetylation and methylation, respectively. Partial compounds were evaluated for antibacterial, anti-inflammatory, and cytotoxic activities. Vineomycinone B2 (), fridamycin D (), and 6-hydroxytetrangulol () displayed broad-spectrum antibacterial activities against , methicillin-resistant and pv. . Furthermore, urdamycin Y () exhibited potent inhibition on NO production, with an IC value of 4.8 M, which was comparable to that of Bay11-7082 with an IC value of 2.1 µM. Subsequently, the possible anti-inflammatory mechanism of urdamycin Y () was explored by molecular docking simulation. Finally, most of the tested metabolites showed significant cytotoxic activities against HCT-116, HT-29, and A375. Notably, 6-hydroxytetrangulol () and the acetyl derivative showed extremely strong cytotoxic activities against HCT-116, with IC values of 9.8 and 2.2 µM, respectively. Moreover, showed extremely strong cytotoxic activity against A375 (IC <0.2 µM), and the conceivable cytotoxic activity mechanism was also proposed by molecular docking. These findings indicated metabolites of insect-associated BYF-106 might be a potential source for developing new bioactive drugs in food, agriculture, and biomedical fields.IMPORTANCEFrequent attention to soil microorganisms has led to the rediscovery of known compounds. By contrast, insect-associated have been shown to produce a more diverse array of unique bioactive secondary metabolites compared to soil . In our ongoing effort to explore structurally diverse bioactive natural products from termite-associated , we discovered that the strain BYF-106 exhibited potent bioactivity. Chemical investigation of BYF-106 resulted in the isolation of two new C-glycoside angucycline-related analogs: urdamycin Y () and grincamycin W (). In addition, four new derivative compounds (, , , and ) were synthesized through acetylation and methylation, respectively. Urdamycin Y () exhibited a strong inhibitory effect on NO production, and most of the tested metabolites showed significant cytotoxic activity. These findings indicate that the metabolites of BYF-106 may offer promising avenues for the exploration and development of new bioactive drugs.