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

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ABSTRACT Two new C-glycoside angucycline-related analogs, urdamycin Y ( 1 ) and grincamycin W ( 2 ), as well as eight known metabolites ( 3–10 ), were identified from termite-associated Streptomyces lannensis BYF-106 based on global natural products social molecular networking (GNPS). The putative biosynthetic pathways of urdamycin Y ( 1 ) and grincamycin W ( 2 ) were proposed using bioinformatic analysis of the full genome of S. lannensis BYF-106. In addition, four new derivative compounds ( 4A , 5A , 6A, and 6B ) were synthesized via acetylation and methylation, respectively. Partial compounds were evaluated in vitro for antibacterial, anti-inflammatory, and cytotoxic activities. Vineomycinone B2 ( 3 ), fridamycin D ( 4 ), and 6-hydroxytetrangulol ( 5 ) displayed broad-spectrum antibacterial activities against S. aureus , methicillin-resistant S. aureus, and P. syringae pv. actinidae . Furthermore, urdamycin Y ( 1 ) exhibited potent inhibition on NO production, with an IC 50 value of 4.8 µ M, which was comparable to that of Bay11-7082 with an IC 50 value of 2.1 µM. Subsequently, the possible anti-inflammatory mechanism of urdamycin Y ( 1 ) 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 ( 5 ) and the acetyl derivative 5A showed extremely strong cytotoxic activities against HCT-116, with IC 50 values of 9.8 and 2.2 µM, respectively. Moreover, 5A showed extremely strong cytotoxic activity against A375 (IC 50 <0.2 µM), and the conceivable cytotoxic activity mechanism was also proposed by molecular docking. These findings indicated metabolites of insect-associated S. lannensis BYF-106 might be a potential source for developing new bioactive drugs in food, agriculture, and biomedical fields. IMPORTANCE Frequent attention to soil microorganisms has led to the rediscovery of known compounds. By contrast, insect-associated Streptomyces have been shown to produce a more diverse array of unique bioactive secondary metabolites compared to soil Streptomyces . In our ongoing effort to explore structurally diverse bioactive natural products from termite-associated Streptomyces , we discovered that the strain S. lannensis BYF-106 exhibited potent bioactivity. Chemical investigation of BYF-106 resulted in the isolation of two new C-glycoside angucycline-related analogs: urdamycin Y ( 1 ) and grincamycin W ( 2 ). In addition, four new derivative compounds ( 4A , 5A , 6A , and 6B ) were synthesized through acetylation and methylation, respectively. Urdamycin Y ( 1 ) 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.

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