Biosynthesis and engineering of archaeal membrane lipids

Archaea are microorganisms abundant across diverse ecosystems, from oceans and soils to animal microbiomes. Unlike bacteria, plants, animals, and humans, archaea build their cell membranes using unique lipid molecules. These unusual membranes are thought to contribute to their ability to adapt to different environments and may provide clues about the early evolution of life.
This thesis investigates how archaeal membrane lipids are produced and regulated, and whether they can function inside a bacterial cell. In this work, the bacterium Escherichia coli (E. coli) was genetically modified to produce archaeal membrane lipids. The engineered cells produced significant amounts of these lipids and even formed hybrid cardiolipins containing both archaeal and bacterial features. However, archaeal lipids could not completely replace the bacterial membrane components required for survival.
This work also improved the production of more stable archaeal lipids and showed that these lipids can increase stress resistance in E. coli. In addition, new enzymes involved in archaeal cardiolipin biosynthesis were identified in the archaeon Haloferax volcanii.Together, this work advances understanding of archaeal membrane lipid biosynthesis, function, and regulation.