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 <b>6</b> showed weak <i>in vitro</i> inhibition but comparable <i>in vivo</i> insecticidal activity to borrelidin. Comparative efficacy tests via intravenous (i.v.) and intraperitoneal (i.p.) administration in silkworm larvae indicated improved pharmacokinetics for compound <b>6</b>. 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 <i>in vitro</i> screening approaches.