An elongation factor Tu (EF‐Tu) resistant to the EF‐Tu inhibitor GE2270 in the producing organism Planobispora rosea

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Abstract
Using a cell‐free protein‐synthesis system, we have established that the elongation factor (EF) Tu (EF‐Tu) of the actinomycete Planobispora rosea, the producer of the thiazolyl peptide GE2270, a specific EF‐Tu inhibitor, is highly resistant to its own antibiotic, while it is completely inhibited by kirromycin, which is another inhibitor of this factor. P. rosea was found to possess a single tuf gene, located between fus and rpsJ, encoding other components of the protein‐synthesis machinery. The P. rosea tuf gene was expressed as a translations! fusion to maIE in Escherichia coli, and the resulting EF‐Tu with an N‐terminal Gly‐Met extension was able to promote poly(U)‐directed poly(Phe) synthesis in cell‐free systems. This activity was not affected by GE2270, and the recombinant protein was incapable of binding the antibiotic, indicating that the P. rosea EF‐Tu is intrinsically resistant to this inhibitor. Inspection of the translated tuf sequence revealed a number of amino acid substitutions in highly conserved positions. These residues, which are likely to be involved in conferring GE2270 resistance, map in EF‐Tu domain II, as do the only two known mutations conferring resistance to this class of thiazolyl peptides in Bacillus subtilis.

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