Refining Metabolic Mass Transfer for Efficient Biosynthesis of Plant Natural Products in Yeast

Abstract

Plant natural products are important secondary metabolites with several special properties and pharmacological activities, which are widely used in pharmaceutical, food, perfume, cosmetic, and other fields. However, the production of these compounds mainly relies on phytoextraction from natural plants. Because of the low contents in plants, phytoextraction has disadvantages of low production efficiency and severe environmental and ecological problems, restricting its wide applications. Therefore, microbial cell factory, especially yeast cell factory, has become an alternative technology platform for heterologous synthesis of plant natural products. Many approaches and strategies have been developed to construct and engineer the yeast cells for efficient production of plant natural products. Meanwhile, metabolic mass transfer has been proven an important factor to improve the heterologous production. Mass transfer across plasma membrane (trans-plasma membrane mass transfer) and mass transfer within the cell (intracellular mass transfer) are two major forms of metabolic mass transfer in yeast, which can be modified and optimized to improve the production efficiency, reduce the consumption of intermediate, and eliminate the feedback inhibition. This review summarized different strategies of refining metabolic mass transfer process to enhance the production efficiency of yeast cell factory (Figure 1), providing approaches for further study on the synthesis of plant natural products in microbial cell factory.

Developments in Fatty Acid-Derived Insect Pheromone Production Using Engineered Yeasts

“…With such synthetic biology strategies, engineering of S. cerevisiae , Y. lipolytica or other yeasts to produce Lepidopteran sex pheromones has achieved considerable success. With further development and application of advanced yeast tools, such as high throughput screening strategy ( Tan et al, 2020 ), metabolic mass transfer strategy ( Xue et al, 2021 ), and efficient gene editing tools for non-conventional oleaginous yeasts ( Shan et al, 2021 ), large-scale commercial production of sex pheromones in engineered yeasts with a high titer, rate and yield would be possible, and will also facilitate moth-mating disruption using biosynthetic sex pheromones in a cost-efficient manner. In the future, the application of yeast-based sex pheromones will lead to eco-friendly agriculture with a green pest control strategy.…”

Presentation_1.pdf

“…With such synthetic biology strategies, engineering of S. cerevisiae, Y. lipolytica or other yeasts to produce Lepidopteran sex pheromones has achieved considerable success. With further development and application of advanced yeast tools, such as high throughput screening strategy (Tan et al, 2020), metabolic mass transfer strategy (Xue et al, 2021), and efficient gene editing tools for non-conventional oleaginous yeasts (Shan et al, 2021), large-scale commercial production of sex pheromones in engineered yeasts with a high titer, rate and yield would be possible, and will also facilitate mothmating disruption using biosynthetic sex pheromones in a costefficient manner. In the future, the application of yeast-based sex pheromones will lead to eco-friendly agriculture with a green pest control strategy.…”