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 (DGK1^OE ) in spt10Δ yeast. Analyses of ER-stress and autophagy suggest that DGK1^OE 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 DGK1^OE spt10Δ yeast. Overall, our study provides a strategic approach to improve triterpene production by increasing ER biogenesis while limiting ER degradation.

• PMID: 35661158
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Journal Article | Research Support, Non-U.S. Gov't

Authors

Ranganathan PR, Narayanan AK, Nawada N, Rao MJ, Reju KS, Priya S C, Gujarathi T, Manjithaya R, Dodaghatta Krishna VR

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