Discover the maze-like network for glabridin biosynthesis

Area of Science:

• Biochemistry and Synthetic Biology
• Natural Product Biosynthesis
• Metabolic Engineering

Background:

• Flavonoid diversity results from enzymatic modifications of precursor molecules.
• Elucidating complex metabolic networks for pathway design is challenging.
• Understanding glabridin biosynthesis in Glycyrrhiza glabra L. is crucial for its production.

Purpose of the Study:

• To identify and reconstruct the glabridin biosynthetic pathway.
• To enable de novo production of glabridin in yeast.
• To investigate the enzymatic mechanisms underlying glabridin synthesis.

Main Methods:

• Chromosome-scale genome assembly and large-scale transcriptome analysis.
• Analysis of 183 licorice transcriptomes to identify modifying enzymes.
• Reconstruction of the biosynthetic pathway in a yeast heterologous host.

Main Results:

• Identification of four enzyme classes modifying isoflavan scaffolds.
• Validation of six functional pathways within a multi-route tailoring network.
• Discovery of a "protection-deprotection" mechanism involving methylation-demethylation cycles.
• Successful de novo production of glabridin in engineered yeast.

Conclusions:

• The study establishes a biosynthetic paradigm for glabridin synthesis.
• Metabolic redundancy and interconnectivity enhance pathway robustness and yield.
• The findings have broad implications for natural product discovery and biomanufacturing.