Phosphate starvation in fungi induces the replacement of phosphatidylcholine with the phosphorus‐free betaine‐lipid diacylglyceryl‐N,N,N‐trimethylhomoserine (605.22)

Diacylglyceryl‐N,N,N‐trimethylhomoserine (DGTS) is a phosphorus‐free betaine‐lipid analog of phosphatidylcholine (PtdCho) synthesized by many soil bacteria, algae, and non‐vascular plants. Synthesis of DGTS and other phosphorus‐free lipids in bacteria occurs in response to phosphorus (P) deprivation, and results in the replacement of phospholipids by non‐phosphorous lipids. The genes encoding DGTS biosynthetic enzymes have previously been identified and characterized in bacteria and the alga Chlamydomonas reinhardtii. We now report that many fungal genomes, including those of plant and animal pathogens, encode the enzymatic machinery for DGTS biosynthesis, and that fungi synthesize DGTS during P‐limitation. This finding demonstrates that replacement of phospholipids by non‐phosphorous lipids is a strategy used in divergent eukaryotic lineages for the conservation of P under P‐limiting conditions. Mutants of Neurospora crassa were used to show that DGTS synthase encoded by the BTA1 locus is solely responsible for DGTS biosynthesis, and is under the control of the fungal phosphorus‐deprivation regulon, mediated by the NUC‐1/Pho4p transcription factor. Furthermore, we describe the rational re‐engineering of lipid metabolism in the yeast S. cerevisiae such that PtdCho is completely replaced by DGTS, and show that membrane and organelle biogenesis are largely unaffected in the engineered strain. Grant Funding Source : National Institutes of Health