De novosynthesis of fatty acids in Archaea via an archaeal fatty acid synthase complex

Abstract

AbstractArchaea synthesize membranes using isoprenoid-based ether lipids, whereas Bacteria and Eukarya usefattyacid-based ester lipids. While the factors responsible for this “lipid divide” remain unclear, this has important implications for understanding the evolutionary history of eukaryotes, which likely originated from within the Archaea and therefore changed membrane composition from isoprenoid-based to fatty acid-based lipids. Here, using13C labelling studies, we demonstrate that the archaeal model organismsSulfolobus acidocaldariusandHaloferax volcaniiare capable ofde novofatty acid synthesis. Biochemical characterization andin vitropathway reconstitution identify the key enzymes of a newly proposed fatty acid synthesis pathway inS. acidocaldariusand show that ketothiolase, ketoacyl-CoA reductase, and hydroxyacyl-CoA dehydratase form a stable assembly mediated by a DUF35 domain protein, which represents the first characterization of an archaeal fatty acid synthase complex. The final step is catalysed by an NADPH-dependent enoyl-CoA reductase. Deletion of the enoyl-CoA reductase demonstrate that this pathway operatesin vivoin S. acidocaldarius. The presented results including phylogenetic analysis reveal that the potential to synthesize fatty acids is widespread across archaeal lineages. Collectively, our findings demonstrate that archaea are capable of synthesizing fatty acids, elucidate the molecular mechanisms involved in this process and provide additional insights into the evolutionary histories of fatty acid synthesis in archaea.