A combination of genome mining with OSMAC strategy facilitates the discovery of bioactive metabolites produced from termite‐associated Streptomyces tanashiensis BYF ‐112

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Abstract BACKGROUND Previously, eight new alkaloids were obtained from the fermentation extract of termite‐associated Streptomyces tanashiensis BYF‐112. However, genome analysis indicated the presence of many undiscovered secondary metabolites in S. tanashiensis BYF‐112. RESULTS Herein, 12 new alkaloids, tianwuine A–E (1–5), cephalandole C (6), venezuelines I–L (7–10), N‐(4‐methylphenyl‐2‐hydroxy) formamide (11) and N‐(5‐formyl‐2‐hydroxyphenyl) formamide (12), as well as three known metabolites (13–15) were discovered from BYF‐112 based on a combination of genome mining and the one strain many compounds (OSMAC) strategy. Plausible biosynthetic pathways of 1–13 were proposed using bioinformatic analysis of the full genome of BYF‐112. Partial metabolites were evaluated in vitro for their antibacterial, phytotoxic, and anti‐inflammatory activities. Pyrroloformamide A (14) showed strong antibacterial activities against Staphylococcus aureus, methicillin‐resistant Staphylococcus aureus, Pseudomonas syringae pv. actinidae, Xanthomonas oryzae pv. oryzae and Xanthomonas oryzae pv. oryzicola at a concentration of 50 μg per 6 mm disk. Simultaneously, pyrroloformamide A (14) also had a strong inhibitory effect on the radicle growth of Echinochloa crusgalli with an inhibition rate of 98.01% at a concentration of 100 μg/mL, equivalent to the positive 2,4‐dichlorophenoxyacetic acid. Subsequently, the possible herbicidal mechanism of 14 was explored using molecular docking simulation. In addition, venezueline G (13) displayed a strong inhibitory effect of NO production, with an half‐maximal inhibitory concentration (IC50) value of 2.3 μm, which was comparable with that of BAY 11‐7082 with an IC50 value of 2.1 μm. CONCLUSION These findings revealed a perspective for the development of novel bioactive drugs in the food, agricultural, and biomedical fields utilizing the metabolites of BYF‐112. © 2025 Society of Chemical Industry.

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