Characterization of the mechanism for the goadsporin self-resistance

Goadsporin is one of ribosomally synthesized and post-translationally modified peptides (RiPPs) produced by Streptomyces sp. TP-A0584. This compound induces morphogenesis and secondary metabolism in actinomycetes at the concentration of less than 1 mM, while it also exhibited antibacterial activity at higher concentration. As goadsporin is effective against various actinomycetes including Streptomyces lividans TK23 and Streptomyces coelicolor A3(2), this molecule would potentially be used to activate the cryptic secondary metabolism in actinomycetes. However, the mode of action for this compound is still unknown because the molecular target of goadsporin had not been identified yet.

 In the goadsporin biosynthetic gene cluster, we have identified godI as a gene for self-resistance (1). godI encodes a protein homologous to Ffh, a bacterial version of signal recognition particle (SRP) protein. In addition, draft genome sequencing of TP-A0584 strain revealed the presence of another ffh gene, which also encoded SRP protein highly homologous to GodI. This observation suggested that the target of goadsporin was Ffh and producing strain had evolved godI from canonical ffh for the defense against goadsporin. To examine our hypothesis, we performed surface plasmon resonance based Biacore analysis to detect the interaction between Ffh and goadsporin.

(1)  Onaka, H. et al. Microbiology 151, 3923-3933 (2005)