Understanding how bacteria synthesize common antibiotics has led to the engineered creation of an even more potent compound, reports Nature Chemical Biology online this week. The ability to manipulate this bacterial pathway should provide new options in the fight against bacteria.
The antibiotic kanamycin is commonly used in the lab as a generic reporter on the successful insertion of a new gene into a bacterium. Despite its prevalence, and the existence of several related natural products as clues to the natural synthetic process, the way in which bacteria make this compound has remained unclear.
Now Jae Kyung Sohng, Yeo Joon Yoon and colleagues report genetic and biochemical evidence that elucidate the entire biosynthetic path to this compound. Surprisingly, they find that the kanamycin family of compounds is made using two parallel pathways that are controlled by a single enzyme. By replacing this key enzyme or inserting others at the end of the path, the authors are able to alter the compound’s structure, creating bacterial routes to the clinically valuable compounds tobramycin and amikacin. They found that one engineered compound, 1-N-AHBA-kanamycin X, even showed greater activity than amikacin, suggesting that it might be an important tool in preventing bacterial infection.