Engineering of cis-Element in Saccharomyces cerevisiae for Efficient Accumulation of Value-Added Compound Squalene via Downregulation of the Downstream Metabolic Flux

• DOI: 10.1021/acs.jafc.1c04978
• Publication Date: 2021-10-19T20:23:24Z
• Authors: Chenyao Zhou; Mingjie Li; Surui Lu; Yanfei Cheng; Xuena Guo; Xiaoxian He; Zhaoyue Wang; Xiu-Ping He
• Keywords: Squalene; Lanosterol; Metabolic Engineering; Ergosterol

Transcriptional downregulation is widely used for metabolic flux control. Here, marO, a cis-element of Escherichia colimar operator, was explored to engineer promoters Saccharomyces cerevisiae downregulation. First, the ADH1 promoter (PADH1) and its enhanced variant PUADH1 were engineered by insertion marO into different sites, which resulted in decrease both gfp5 transcription GFP fluorescence intensity various degrees. Then, applied native ERG1 ERG11 due their importance accumulation value-added intermediates squalene lanosterol. Elevated content (4.9-fold) or lanosterol (4.8-fold) 91 28% ergosterol from marO-engineered PERG1(M5) PERG11(M3), respectively, indicating validity Furthermore, production 3.53 g/L cane molasses, cheap bulk substrate, suggested cost-effective promising potential production.