Structural Insights into Novel Esterase

Chloramphenicol (Cm) and florfenicol (Ff) are broad‐spectrum antibiotics that inhibit protein synthesis. Both antibiotics are a bacteriostat but differ in their chemical structure in that a fluoro group is attached to C3 of Ff. Specifically, both antibiotics prevent a formation of the peptide bond by irreversibly binding to a receptor site on the 50S subunit of the bacterial ribosome. It is well established that chloramphenicol acetyltransferase inactivates Cm by first recognizing the hydroxyl group of C3 in Cm and then specifically acetylating the hydroxyl group. Due to this specificity, Ff cannot serve as a substrate of chloramphenicol acetyltransferase. Interestingly, a novel esterase, which was recently characterized by metagenome screening, inactivates both antibiotics possibly by hydrolysis of those antibiotics, suggesting that this esterase could be a novel enzyme in inactivating both Cm and Ff. Sequence analysis indicates that its sequence is highly similar to those of microbial hormone senstive lipase. Consistent with this comparison, a newly identified esterase contains Ser156 in the GxSxG motif and Asp252 and His282, the catalytic triad conserved in the family of microbial hormone sensitive lipase. In order to understand this novel enzymatic feature, we are carrying out X‐ray crystallographic analysis. Our studies will provide structural insights into antibiotics hydrolysis. Support or Funding Information This work was supported by a grant from the Next‐Generation BioGreen 21 Program, Rural Development Administration, KOREA .