Ladderane phospholipids form a densely packed membrane with normal hydrazine and anomalously low proton/hydroxide permeability

Significance

Ladderane lipids represent exotic natural products containing highly strained, concatenated cyclobutane rings, a motif that has not been found in any other natural products. These lipids are exclusively found in bacteria that carry out anaerobic ammonium oxidation (anammox), suggesting a biological role in the anammox process. The relationship between molecular structure and this metabolism remains unexplored due to a lack of natural lipid material to study. We use an efficient chemical synthesis to create large quantities of pure ladderane lipids for biophysical analysis. This analysis reveals some unusual properties of membranes composed of ladderane lipids. Significantly, ladderane membranes have low proton permeability, which would slow the breakdown of the proton gradient used to synthesize ATP during the slow anammox metabolism.