Role of diacylglycerol kinase in autophagy, ER biogenesis, and triterpene metabolism.

Abstract

Saccharomyces cerevisiae is widely used for producing various triterpenes by exploiting its native mevalonate/ergosterol pathway. Yeasts that accumulate phospholipids can produce more triterpenes. Our recent study demonstrated that a high phospholipid-accumulating yeast phenotype, as in spt10Δ yeast, results in increased endoplasmic reticulum (ER) biogenesis, resulting in ER expansion. However, the spt10Δ strain also exhibits high reticulophagy. Dgk1 (diacylglycerol kinase) is an important enzyme in lipid metabolism, which synthesizes phosphatidic acid (PA) by phosphorylating diacylglycerol (DG). We demonstrate that spt10Δ yeast with increased Dgk1 activity offer two desired results, (i) a highly expanded ER, due to redirection of the lipid pathway away from triglycerides towards phospholipid synthesis, increasing ER biogenesis; and (ii) decreased reticulophagy, by increasing the PA pool that activates TOR complex-mediated autophagy suppression. It was speculated that more ER-bound pathway enzymes can fit in the expanded ER, and the mevalonate-ergosterol pathway, being ER bound, might have higher activity. This was demonstrated by the co-expression of Dgk1 and plant triterpene synthase in spt10Δ yeast, which shows a high accumulation of plant triterpene.