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

• Published in: Nature communications 2022-12, Vol.13 (1), p.7740-15, Article 7740
• Main Authors: Yuan, Wei, Jiang, Chenjian, Wang, Qin, Fang, Yubo, Wang, Jin, Wang, Meng, Xiao, Han
• Format: Article
• Language: English
• Subjects: 49; 49/31; 49/56; 631/208/212/748; 631/553/552; 631/61/318; 631/92/349/977; Accumulation; Acids; Agaricales; Biosynthesis; Cytochrome; Cytochrome P-450 Enzyme System - genetics; Cytochrome P-450 Enzyme System - metabolism; Cytochrome P450; Cytochromes P450; Genomes; Humanities and Social Sciences; Industrial engineering; Low level; Manufacturing engineering; Microorganisms; multidisciplinary; Mushrooms; Reishi - genetics; Reishi - metabolism; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Science; Science (multidisciplinary); Supply chains; Triterpenes - metabolism; Triterpenoids; Yeast; Yeasts
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-35500-1

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. The biosynthetic pathway of type II ganoderic acids (GAs) in Ganoderma lucidum , a traditional medicinal mushroom, is unknown. Here, the authors assemble the genome of type II GAs accumulating accession, identify CYPs involving in type II GAs biosynthesis, and achieve their production in engineered baker’s yeast.