Student Research: Magdalena Todorinova & Dr. Kara Jaremko
Inhibition of Various Acyl-Acyl Carrier Protein Synthetases to Study Fatty Acid Recycling
Fatty acid synthetase (or FAS) is a well-known drug target for antibiotics, as fatty acids are essential for the survival of most organisms. Yet, some gram-negative bacteria can overcome this process by recycling free fatty acids from the environment and incorporating them into lipids by use of acyl-acyl carrier protein synthetase enzymes (AasS). Dr. Jaremko and Magdalena use a previously synthesized inhibitor of AasS, C10-AMS, to study the role of AasS in fatty acid recycling, inhibit their catalytic activity, and provide useful insight for antibiotic development.
Magdalena described this research to focus on four AasS enzymes from Chlamydia trachomatis, Neisseria gonnorrhoeae, and Alistipides finegoldii. Each of these bacteria was expressed, purified, and tested with C10-AMS to test its effectiveness while inhibiting their catalytic activity; all four AasS enzymes were successfully inhibited. This result suggests that C10-AMS can be used to study the role of AasS in fatty acid recycling and provides useful insight for antibiotic development. Magdalena shared that the future of this research will be the use of C10-AMS to identify new AasS enzymes that may have been misannotated in previous research. This will determine whether different AasS enzymes have preferences for inhibitors with various acyl chain lengths, such as C4-AMS, C6-AMS, and C14-AMS.
