Engineering Critical Enzymes and Pathways for Improved Triterpenoid Biosynthesis in Yeast

Area of Science:

• Metabolic Engineering
• Synthetic Biology
• Biotechnology

Background:

• Triterpenoids are diverse plant-derived compounds with significant biological activities.
• Heterologous production of triterpenoids in Saccharomyces cerevisiae has been established.
• Previous efforts have improved yields from mg/L to g/L scale.

Purpose of the Study:

• To review strategies for enhancing triterpenoid yield in S. cerevisiae through enzyme engineering.
• To address challenges and explore prospects for industrial-scale triterpenoid production.

Main Methods:

• Engineering enzymes involved in triterpenoid biosynthesis.
• Optimizing yeast metabolism to increase precursor supply (2,3-oxidosqualene).
• Modifying native sterol pathways to reduce competition.

Main Results:

• Significant yield improvements achieved, reaching gram-per-liter scale.
• Demonstrated success in overcoming production hurdles via enzyme design.
• Identified key strategies for enhancing triterpenoid production.

Conclusions:

• Enzyme engineering is a viable strategy for industrial triterpenoid production.
• Further enhancements are possible by optimizing precursor supply, reactions, and competing pathways.
• S. cerevisiae serves as a powerful platform for producing valuable triterpenoids.