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

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 (IC ₅₀ ) value of 2.3 μm, which was comparable with that of BAY 11-7082 with an IC ₅₀ 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.
(© 2025 Society of Chemical Industry.)