Premium
Cover Picture: Exploring the Substrate Promiscuity of Drug‐Modifying Enzymes for the Chemoenzymatic Generation of N‐Acylated Aminoglycosides (ChemBioChem 1/2010)
Author(s) -
Green Keith D.,
Chen Wenjing,
Houghton Jacob L.,
Fridman Micha,
GarneauTsodikova Sylvie
Publication year - 2010
Publication title -
chembiochem
Language(s) - English
Resource type - Reports
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200990088
Subject(s) - promiscuity , cover (algebra) , enzyme , drug , substrate (aquarium) , chemistry , substrate specificity , combinatorial chemistry , stereochemistry , biochemistry , computational biology , pharmacology , biology , engineering , mechanical engineering , ecology
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.