Biosynthesis of mushroom-derived type II ganoderic acids by engineered yeast

Area of Science:

• Biotechnology
• Mycology
• Metabolic Engineering

Background:

• Type II ganoderic acids (GAs) are bioactive triterpenoids from Ganoderma mushrooms with significant therapeutic potential.
• Efficient production is hindered by challenges in genetic manipulation, low yields, supply chain vulnerabilities, and an unclear biosynthetic pathway.

Purpose of the Study:

• To overcome limitations in type II GA production by developing a microbial cell factory.
• To elucidate key enzymes in the type II GA biosynthetic pathway.
• To enable scalable production of specific type II GAs.

Main Methods:

• Genome assembly of a type II GA-accumulating Ganoderma lucidum accession.
• Screening of Ganoderma-derived cytochrome P450 enzymes (CYPs) in baker's yeast.
• Identification of crucial CYPs for type II GA biosynthesis.
• Engineering of baker's yeast for the bioproduction of GA-Y and GA-Jb.

Main Results:

• Successfully identified key cytochrome P450 enzymes involved in type II GA biosynthesis.
• Engineered baker's yeast to produce GA-Y and GA-Jb.
• Achieved higher production levels of GA-Y and GA-Jb in engineered yeast compared to the farmed mushroom.

Conclusions:

• The study successfully developed a microbial cell factory for producing type II GAs, overcoming natural production limitations.
• Findings contribute to a deeper understanding of the complex ganoderic acid biosynthetic network.
• This approach paves the way for the commercial-scale production of valuable ganoderic acids.