[Chemical approach to analyze the physiological function of phospholipids with polyunsaturated fatty acyl chain]

Polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) occur in biological membranes as acyl groups of phospholipids and exhibit remarkable physiological activities. In human, they have various beneficial effects on health such as protective effects against cardiovascular disease, inflammation, and cancer. We have been studying their physiological functions in bacteria, which have a much simpler membrane structure than eukaryotes. We found that the cell division of a marine bacterium, Shewanella livingstonensis Ac10, is inhibited and shows growth retardation by disruption of its EPA biosynthesis genes. We synthesized a fluorescent analog of EPA-containing phospholipids (EPA-PLs) as a chemical probe to analyze their subcellular distribution and found that it is localized at the center of the cell undergoing cell division. This localization was shown to depend on the structure of the hydrocarbon chain of the phospholipids. We also examined the effects of EPA-PLs on the folding of Omp74, a major membrane protein of this bacterium, by using liposomes and found that EPA-PLs facilitated the folding process. The results imply that EPA-PLs function as a chemical chaperone in the folding of membrane proteins. These findings would contribute to understanding of the physiological function of phospholipids with polyunsaturated fatty acyl chains in various biological membranes.