A lecithin cholesterol acyltransferase-like gene mediates diacylglycerol esterification in yeast

The terminal step in triglyceride biosynthesis is the esterification of dia cylglycerol. To study this reaction in the model eukaryote, Saccharomyces c erevisiae, we investigated five candidate genes with sequence conservation to mammalian acyltransferases. Four of these genes are similar to the recen tly identified acyl-CoA diacylglycerol acyltransferase and, when deleted, r esulted in little or no decrease in triglyceride synthesis as measured by i ncorporation of radiolabeled oleate or glycerol. By contrast, deletion of L RO1, a homolog of human lecithin cholesterol acyltransferase, resulted in a dramatic reduction in triglyceride synthesis, whereas overexpression of LR O1 yielded a significant increase in triglyceride production. In vitro micr osomal assays determined that Lro1 mediated the esterification of diacylgly cerol using phosphatidylcholine as the acyl donor. The residual triglycerid e biosynthesis that persists in the LRO1 deletion strain is mainly acyl-CoA -dependent and mediated by a gene that is structurally distinct from the pr eviously identified mammalian diacylglycerol acyltransferase. These mechani sms may also exist in mammalian cells.