Horizontal acquisition of prokaryotic hopanoid biosynthesis reorganizes membrane physiology driving lifestyle innovation in a eukaryote

Horizontal gene transfer is a source of metabolic innovation and adaptation to new environments. How new metabolic functionalities are integrated into host cell biology is largely unknown. Here, we probe this fundamental question using the fission yeast Schizosaccharomyces japonicus, which has acquired a squalene-hopene cyclase Shc1 through horizontal gene transfer. We show that Shc1-dependent production of hopanoids, mimics of eukaryotic sterols, allows S. japonicus to thrive in anoxia, where sterol biosynthesis is not possible. We demonstrate that glycerophospholipid fatty acyl asymmetry, prevalent in S. japonicus, is crucial for accommodating both sterols and hopanoids in membranes, and explain how Shc1 functions alongside the sterol biosynthetic pathway to support membrane properties. Reengineering experiments in the sister species S. pombe show that hopanoids entail new traits in a “naïve” organism, but the acquisition of a new enzyme may trigger profound reorganization of the host metabolism and physiology.