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

Wei Yuan, Chenjian Jiang, Qin Wang, Yubo Fang, Jin Wang, Meng Wang () and Han Xiao ()
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Wei Yuan: University of Chinese Academy of Sciences
Chenjian Jiang: Shanghai Jiao Tong University
Qin Wang: Shanghai Jiao Tong University
Yubo Fang: Shanghai Jiao Tong University
Jin Wang: University of Chinese Academy of Sciences
Meng Wang: Chinese Academy of Sciences
Han Xiao: Shanghai Jiao Tong University

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract Type II ganoderic acids (GAs) produced by the traditional medicinal mushroom Ganoderma are a group of triterpenoids with superior biological activities. However, challenges in the genetic manipulation of the native producer, low level of accumulation in the farmed mushroom, the vulnerabilities of the farming-based supply chain, and the elusive biosynthetic pathway have hindered the efficient production of type II GAs. Here, we assemble the genome of type II GAs accumulating G. lucidum accession, screen cytochrome P450 enzymes (CYPs) identified from G. lucidum in baker’s yeast, identify key missing CYPs involved in type II GAs biosynthesis, and investigate the catalytic reaction sequence of a promiscuous CYP. Then, we engineer baker’s yeast for bioproduciton of GA-Y (3) and GA-Jb (4) and achieve their production at higher level than those from the farmed mushroom. Our findings facilitate the further deconvolution of the complex GA biosynthetic network and the development of microbial cell factories for producing GAs at commercial scale.

Date: 2022
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DOI: 10.1038/s41467-022-35500-1

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