One of the key aspects that defines
a cell as a living entity is
its ability to self-reproduce. In this process, membrane biogenesis
is an essential element. Here, we developed an in vitro phospholipid biosynthesis pathway based on a cascade of eight enzymes,
starting from simple fatty acid building blocks and glycerol 3-phosphate.
The reconstituted system yields multiple phospholipid species that
vary in acyl-chain and polar headgroup compositions. Due to the high
fidelity and versatility, complete conversion of the fatty acid substrates
into multiple phospholipid species is achieved simultaneously, leading
to membrane expansion as a first step toward a synthetic minimal cell.
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.
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