Calditol-linked membrane lipids are required for acid tolerance inSulfolobus acidocaldarius

Significance It is thought that the distinct ether lipid membranes of archaea allow them to thrive in environmental extremes. However, it has been difficult to demonstrate this physiological role directly. Here, we identify a protein required for the biosynthesis of a unique archaeal lipid head group, calditol, whose production was considered to be restricted to a subset of archaeal thermoacidophiles. We show that deletion of this protein inSulfolobus acidocaldarius prevents production of calditol-linked membrane lipids and, in turn, inhibits cell growth at extremely low pH. Our findings also suggest that archaea more broadly, like bacteria, employ radicalS -adenosylmethionine proteins to modify membrane lipids in ways that confer protective effects when environmental conditions, such as pH, fluctuate significantly.