As renewable biomass, lignocellulose remains one of the major choices for most countries in tackling global energy shortage and environment pollution. Efficient utilization of xylose, an important monosaccharide in lignocellulose, is essential for the production of high-value compounds, such as ethanol, lipids, and isoprenoids. Protopanaxadiol (PPD), a kind of isoprenoids, has important medical values and great market potential. The engineered protopanaxadiol-producing Yarrowia lipolytica strain, which can use xylose as the sole carbon source, was constructed by introducing xylose reductase (XR) and xylitol dehydrogenase (XDH) from Scheffersomyces stipitis, overexpressing endogenous xylulose kinase (ylXKS) and heterologous PPD synthetic modules, and then 18.18 mg/L of PPD was obtained. Metabolic engineering strategies such as regulating cofactor balance, enhancing precursor flux, and improving xylose metabolism rate via XR (K270R/N272D) mutation, the overexpression of tHMG1/ERG9/ERG20 and transaldolase (TAL)/transketolase (TKL)/xylose transporter (TX), were implemented to enhance PPD production. The final Y14 strain exhibited the greatest PPD titer from xylose by fed-batch fermentation in a 5-L fermenter, reaching 300.63 mg/L [yield, 2.505 mg/g (sugar); productivity, 2.505 mg/L/h], which was significantly higher than the titer of glucose fermentation [titer, 167.17 mg/L; yield, 1.194 mg/g (sugar); productivity, 1.548 mg/L/h]. The results showed that xylose was more suitable for PPD synthesis than glucose due to the enhanced carbon flux towards acetyl-CoA, the precursor for PPD biosynthetic pathway. This is the first report to produce PPD in Y. lipolytica with xylose as the sole carbon source, which developed a promising strategy for the efficient production of high-value triterpenoid compounds.

Saccharomyces cerevisiae is currently one of the most important foreign gene expression systems. S. cerevisiae is an excellent host for high-value metabolite cell factories due to its advantages of simplicity, safety, and nontoxicity. A promoter, as one of the basic elements of gene transcription, plays an important role in regulating gene expression and optimizing metabolic pathways. Promoters control the direction and intensity of transcription, and the application of promoters with different intensities and performances will largely determine the effect of gene expression and ultimately affect the experimental results. Due to its significant role, there have been many studies on promoters for decades. While some studies have explored and analyzed new promoters with different functions, more studies have focused on artificially modifying promoters to meet their own scientific needs. Thus, this article reviews current research on promoter engineering techniques and related natural promoters in S. cerevisiae. First, we introduce the basic structure of promoters and the classification of natural promoters. This section will help in understanding future studies on promoters. The classification of various promoter strategies is then reviewed. In this section, the research of each promoter engineering strategy is divided into static regulation and dynamic regulation respectively. Finally, by grouping related articles together using various strategies, this review anticipates the future development direction of promoter engineering.