Engineering Saccharomyces cerevisiae for Efficient Liquiritigenin Production

Area of Science:

• Metabolic Engineering
• Synthetic Biology
• Natural Product Biosynthesis

Background:

• Liquiritigenin, a flavonoid from licorice, faces production challenges due to extraction inefficiencies and low microbial titers.
• Current heterologous production of liquiritigenin is limited to the proof-of-concept stage, insufficient for commercial viability.

Purpose of the Study:

• To develop an efficient microbial production system for liquiritigenin.
• To engineer *Saccharomyces cerevisiae* for enhanced liquiritigenin synthesis.
• To establish a novel metabolic strategy for flavonoid production.

Main Methods:

• Re-engineering the galactose induction system in *Saccharomyces cerevisiae* for improved decoupling of growth and production phases.
• Modification of a naringenin-producing strain for liquiritigenin pathway redirection.
• Development of a dual NADPH supply system to boost production.
• Introduction of the aromatic ester model for pathway optimization.

Main Results:

• Engineered *Saccharomyces cerevisiae* achieved a liquiritigenin titer of 867.67 mg/L in a 5 L fermenter.
• The re-engineered induction system and dual NADPH supply enhanced liquiritigenin production and ratio.
• The aromatic ester model provided a generalizable strategy for flavonoid synthesis.

Conclusions:

• This study demonstrates a successful strategy for efficient microbial production of liquiritigenin, surpassing conventional extraction limitations.
• The developed genetic and metabolic modifications offer valuable insights for the synthesis of flavonoids and other natural products.
• The engineered yeast platform provides a sustainable and scalable alternative for liquiritigenin manufacturing.