Threonyl-tRNA Synthetase Is the Target of Borrelidin Insecticidal Activity against Silkworms.

We explore borrelidin and semisynthetic derivatives as promising pesticide candidates targeting threonyl-tRNA synthetase (ThrRS). Enzymatic inhibition assays and pull-down assays supported ThrRS as the target of borrelidins for insecticidal activity. Interestingly, derivative 6 showed weak in vitro inhibition but comparable in vivo insecticidal activity to borrelidin. Comparative efficacy tests via intravenous (i.v.) and intraperitoneal (i.p.) administration in silkworm larvae indicated improved pharmacokinetics for compound 6. These findings highlight ThrRS as a valuable insecticidal target and demonstrate the effectiveness of our original silkworm-based screening platform in identifying lead compounds with favorable pharmacokinetics that are often overlooked by conventional in vitro screening approaches.