Borrelidin is an unusual nitrile-containing metabolite isolated from Streptomyces. Borrelidin is an important lead for antimalarial discovery, displaying activity against drug-resistant Plasmodia.
Borrelidin is soluble in ethanol, methanol, DMF and DMSO.
| Mechanism of Action | Borrelidin is a selective inhibitor of bacterial and eukaryal threonyl-tRNA synthetase and is a very potent angiogenesis inhibitor and induces apoptosis of the capillary tube-forming cells. |
| Microbiology Applications | Aminoacyl tRNA synthetases (aaRSs) attach the appropriate amino acids to the tRNAs. This crucial step in protein synthesis is an attractive target for antimicrobials. Borrelidin is known to target Threonyl-tRNA synthetase (ThrRS) in its array of bioactivity, which includes antibacterial, antiviral, antimalarial, insecticidal, herbicidal and antiangiogenic activity. However, there is still some discussion on the location of its binding site on ThrRS. Beginning from a prediction of molecular docking on Escherichia coli's ThrRS, Li et al. continued working with mutagenesis to identify residues relevant to Borrelidin's activity. Their conclusion does not match a previous proposal by Ruan et al. However, it is submitted that the two proposed clusters may be associated with each other, and are both related to Borrelidin resistance (Ming et al, 2024). |
| References |
A unique hydrophobic cluster near the active site contributes to differences in borrelidin inhibition among threonyl-tRNA synthetases. Ruan T. et al. , J. Biol. Chem. 2005, 280, 571. Ming L et al (2014) Identification of Borrelidin binding site on threonyl-tRNA synthetase. Biochem. Biophys. Res. Comm. 451(4):485-490 |