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Diacylglycerol kinase alleviates autophagic degradation of the endoplasmic reticulum in SPT10‐deficient yeast to enhance triterpene biosynthesis

A recent study showed that deletion of the gene encoding the transcription regulator SuPpressor of Ty10 (SPT10) increases total phospholipids, and our previous study established a critical link between phospholipids… Click to show full abstract

A recent study showed that deletion of the gene encoding the transcription regulator SuPpressor of Ty10 (SPT10) increases total phospholipids, and our previous study established a critical link between phospholipids and the mevalonate/ergosterol (MEV/ERG) pathway, which synthesises triterpenes. This study aims to use spt10Δ yeast to improve triterpene production. Though MEV/ERG pathway was highly expressed in spt10Δ yeast, results showed insufficient accumulation of key metabolites and also revealed massive endoplasmic reticulum (ER) degradation. We found a stable, massive ER structure when we overexpressed diacylglycerol kinase1 (DGK1OE) in spt10Δ yeast. Analyses of ER‐stress and autophagy suggest that DGK1OE in the spt10Δ strain decreased autophagy, resulting in increased MEV/ERG pathway activity. Heterologous expression of β‐amyrin synthase showed significant production of the triterpene β‐amyrin in DGK1OE spt10Δ yeast. Overall, our study provides a strategic approach to improve triterpene production by increasing ER biogenesis while limiting ER degradation.

Keywords: endoplasmic reticulum; triterpene; spt10; spt10 yeast; yeast; degradation

Journal Title: FEBS Letters
Year Published: 2022

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