Researcher Liu Hongwei’s team from the Institute of Microbiology, Chinese Academy of Sciences clarified the diterpene biosynthesis network of Hericium erinaceus against Alzheimer’s disease, and constructed "non-natural" active diterpenoids.

Editor in charge: Food Science

The guanane-type diterpene compounds have a unique 5-6-7 tricyclic skeleton.

The research team of Hongwei Liu from the Institute of Microbiology, Chinese Academy of Sciences has long been committed to the discovery, active mechanism, and biosynthesis of active ornithane diterpenes.

At the same time, based on the heterogeneity of the substrates of glycosyltransferase EriJ, dehydrogenase EriH and FAD-dependent oxidase EriM, strains that produce new structural "non-natural" analogs were designed and constructed

The above research results were published in Acta Pharmaceutica Sinica B , a TOP journal in Pharmacy District I in September 2021 , with the title "Reconstitution of biosynthetic pathway for mushroom-derived cyathane diterpenes in yeast and generation of new "non-natural" analogues", China Ma Ke (now a postdoctoral fellow at Peking University), a doctoral student at the State Key Laboratory of Mycology, Institute of Microbiology, Academy of Sciences, is the first author of the paper, and researcher Liu Hongwei is the corresponding author of the paper

Abstract original

Reconstitution of biosynthetic pathway for mushroom-derived cyathane diterpenes in yeast and generation of new “non-natural” analogues

Ke Ma, Yuting Zhang, Cui Guo, Yanlong Yang, Junjie Han, Bo Yu, Wenbing Yin, Hongwei Liu

Abstract
Mushroom-derived cyathane-type diterpenes possess unusual chemical skeleton and diverse bioactivities.
To efficiently supply bioactive cyathanes for deep studies and explore their structural diversity, de novo synthesis of cyathane diterpenes in a geranylgeranyl pyrophosphate engineered Saccharomyces cerevisiae is investigated.
Aided by homologous analyses , one new unclustered FAD-dependent oxidase EriM accounting for the formation of allyl aldehyde and three new NADP(H)-dependent reductases in the biosynthesis of cyathanes are identified and elucidated.
By combinatorial biosynthetic strategy, S.
cerevisiae strains generating twenty-two cyathane-type diterpenes, including seven “unnatural” cyathane xylosides (12, 13, 14a, 14b, 19, 20, and 22) are established.
Compounds 12–14, 19, and 20 show significant neurotrophic effects on PC12 cells in the dose of 6.
3–25.
0 μmol/L.
These studies provide new insights into the divergent biosynthesis of mushroom-originated cyathanes and a straightforward approach to produce bioactive cyathane-type diterpenes.