SignificanceEscherichia coli has been engineered toward an archaebacterium with an unprecedented high level of archaeal ether phospholipids. The obtained cells stably maintain a mixed heterochiral membrane. This finding challenges theories that assume that intrinsic instability of mixed membranes led to the “lipid divide” and the subsequent differentiation of bacteria and archaea. Furthermore, this study paves the way for future membrane engineering of industrial production organisms with improved robustness.

Highlights d Identification of DGGGP synthase as a member of the UbiA superfamily d Structures determination of Apo-and lipid bound states of DGGGPase d Functional and structural insights into lipid modifying enzyme in three kingdoms d Archaeal lipid biosynthesis, remodeling, and membrane adaptation in cell membrane

Studies on vesicle formation by the Coat Protein I (COPI) complex have contributed to a basic understanding of how vesicular transport is initiated. Phosphatidic acid (PA) and diacylglycerol (DAG) have been found previously to be required for the fission stage of COPI vesicle formation. Here, we find that PA with varying lipid geometry can all promote early fission, but only PA with shortened acyl chains promotes late fission. Moreover, diacylglycerol (DAG) acts after PA in late fission, with this role of DAG also requiring shorter acyl chains. Further highlighting the importance of the short-chain lipid geometry for late fission, we find that shorter forms of PA and DAG promote the vesiculation ability of COPI fission factors. These findings advance a general understanding of how lipid geometry contributes to membrane deformation for vesicle fission, and also how proteins and lipids coordinate their actions in driving this process.

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