Aquastatin C, a new glycoaromatic derivative from Sporothrix sp. FN611

Abstract

Bacterial fatty acid synthesis (FAS) is an attractive antibacterial target, as FAS is organized differently in bacteria and mammals.1, 2 Fatty acid biosynthesis in bacteria is crucial for the production of a number of lipid-containing components, including the cell membrane. The bacterial fatty acid system (FAS II) uses discrete monofunctional enzymes, which operate in conjunction with acyl carrier protein (ACP)-associated substrates, whereas mammalian fatty acid synthase (FAS I) is mediated by a single multifunctional enzyme–ACP complex. The differences in prokaryote and eukaryote fatty acid biosynthesis provide an attractive opportunity for selective FAS II inhibition, which is a potential strategy for the development of antibacterial agents. Bacterial enoyl-ACP reductase, which catalyzes the final and rate-limiting step in type II FAS, has been validated as a novel target for the development of antibacterial drugs.3, 4 Three isoforms, FabI, FabK and FabL, have been detected in enoyl-ACP reductase. Most of bacteria including Staphylococcus aureus contain FabI, but Streptococcus pneumonia has FabK. Enterococcus faecalis and Pseudomonas aeruginosa were known to contain both FabI and FabK, whereas Bacillus subtilis contains both FabI and FabL. InhA is the FabI homolog from Mycobacterium tuberculosis. Indeed, the antibacterial target of triclosan5 and isoniazid,6 which are currently used antibacterial agents, have been determined to be the FabI and InhA, respectively. Therefore, the enoyl-ACP reductase inhibitors may prove to be interesting lead compounds for the development of effective antibacterial drugs.