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Cover Picture: Exploring the Substrate Promiscuity of Drug-Modifying Enzymes for the Chemoenzymatic Generation of N-Acylated Aminoglycosides (ChemBioChem 1/2010)
The cover picture shows the concept of utilizing enzymes that evolved in bacteria to confer resistance to antibiotics as a chemical tool to generate novel antibacterials with broad-spectrum activity. On p. 119 ff, M. Fridman, S. Garneau-Tsodikova et al. show how two aminoglycoside acetyltransferases (blue on the left and multicolored on the right) isolated from resistant bacterial strains catalyze the regiospecific acyl transfer from an acyl-coenzyme A (the two molecules at the edges of the picture, the acyl atoms are shown in brighter colors) to aminoglycosides to create novel N-acylated antibiotics. On the cover, the aminoglycoside tobramycin (the two molecules in the middle) is modified to yield the 3'- (bottom left) and 6'-N-acylated tobramycin (bottom right). The N-acylated tobramycin analogues exhibit antibacterial activity, as demonstrated by the lysed bacterium at the bottom of the picture.