Archaea-type ether lipids in Bacteria: biosynthesis, processing, and physiological function

• Antragsteller: Privatdozent Dr. Patrick Babinger
• Fachliche Zuordnung: Biochemie
• Förderung: Förderung von 2012 bis 2017
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 222192502

Ether lipids consisting of a sn-glycerol-1-phosphate (G1P) scaffold with attached polyprenyl side chains have been found exclusively within the Archaea and have therefore been considered a hallmark of this phylogenetic domain. We have recently disproved this paradigm by showing that the polyprenylglyceryl phosphate synthase PcrB catalyzes the synthesis of the G1P-based ether lipid heptaprenylglyceryl phosphate (HepGP) in Bacillus subtilis and related Gram-positive species from the domain Bacteria. We have further demonstrated that HepGP is processed in vivo by dephosphorylation and acetylation. Since such modifications have previously not been observed for any ether lipid, we will purify and characterize the involved phosphatase and acetyltransferase enzymes. Moreover, we plan to elucidate the biological function of the novel bacterial ether lipids by analyzing the growth phenotype and membrane composition of various B. subtilis knock-out strains in comparison with wild-type cells. In a database search we have identified a second group of polyprenylglyceryl phosphate synthases in Bacteria, which are found exclusively in Gram-negative species and whose sequences differ considerably from PcrB. We will identify the polyprenyl substrate and the ether lipid product of this uncharacterized group of enzymes and elucidate the structural basis for the substrate specificities of polyprenylglyceryl phosphate synthases from Bacteria in comparison to those of Archaea. Our studies shall provide a comprehensive understanding of the biosynthesis and physiological function of ether lipids in Bacteria.

• DFG-Verfahren: Sachbeihilfen
• Beteiligte Person: Professor Dr. Reinhard Sterner