Simplified route to phospholipid membranes

In biological systems, phospholipids are made by enzymes embedded in preexisting phospholipid membranes. Such circular dependence has hindered the development of methods for making membranes for synthetic cells. Neal K. Devaraj and coworkers at the University of California San Diego get around this challenge by repurposing a water-soluble mycobacterial enzyme called FadD10 (Nat. Commun. 2019, DOI: 10.1038/s41467-018-08174-x). This enzyme uses dodecanoate (shown, DDA) as a substrate to form a fatty acyl adenylate (red with green star), which then reacts with a lysolipid (blue) to form a phospholipid. The resulting phospholipids assemble into vesicle-forming membranes. Vesicles encapsulating FadD10 continue to make phospholipids as long as the researchers supply the reactive precursors. In addition, the researchers were able to make phospholipid vesicles from scratch in the presence of DNA encoding the gene for FadD10. “This work has potential implications for the bottom-up generation of synthetic cells, as it minimizes the compounds required to build and grow membranes,” says Arnold J. M. Driessen, an expert on membrane biology at the University of Groningen. One drawback, according to Pasquale Stano, an expert on minimal cells at the University of Salento, is that the phospholipids were made from precursors that already have hydrophobic chains. “The next step will be synthesizing the long hydrophobic chains from small molecules,” Stano says.