Unraveling the serial glycosylation in the biosynthesis of steroidal saponins in the medicinal plant Paris polyphylla and their antifungal action.
10.1016/j.apsb.2023.05.033
- Author:
Yuegui CHEN
1
;
Qin YAN
1
;
Yunheng JI
2
;
Xue BAI
1
;
Desen LI
1
;
Rongfang MU
1
;
Kai GUO
3
;
Minjie YANG
1
;
Yang TAO
3
;
Jonathan GERSHENZON
4
;
Yan LIU
1
;
Shenghong LI
1
Author Information
1. State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China.
2. Key Laboratory for Plant Diversity and Biogeography of East Asia, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China.
3. State Key Laboratory of Southwestern Chinese Medicine Resources, Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
4. Max Planck Institute for Chemical Ecology, Jena D-07745, Germany.
- Publication Type:Journal Article
- Keywords:
Antifungal activity;
Glycosyltransferases;
Paris polyphylla var. yunnanensis;
Steroidal saponins;
Sugar chain elongation
- From:
Acta Pharmaceutica Sinica B
2023;13(11):4638-4654
- CountryChina
- Language:English
-
Abstract:
Sugar-sugar glycosyltransferases play important roles in constructing complex and bioactive saponins. Here, we characterized a series of UDP-glycosyltransferases responsible for biosynthesizing the branched sugar chain of bioactive steroidal saponins from a widely known medicinal plant Paris polyphylla var. yunnanensis. Among them, a 2'-O-rhamnosyltransferase and three 6'-O-glucosyltrasferases catalyzed a cascade of glycosylation to produce steroidal diglycosides and triglycosides, respectively. These UDP-glycosyltransferases showed astonishing substrate promiscuity, resulting in the generation of a panel of 24 terpenoid glycosides including 15 previously undescribed compounds. A mutant library containing 44 variants was constructed based on the identification of critical residues by molecular docking simulations and protein model alignments, and a mutant UGT91AH1Y187A with increased catalytic efficiency was obtained. The steroidal saponins exhibited remarkable antifungal activity against four widespread strains of human pathogenic fungi attributed to ergosterol-dependent damage of fungal cell membranes, and 2'-O-rhamnosylation appeared to correlate with strong antifungal effects. The findings elucidated the biosynthetic machinery for their production of steroidal saponins and revealed their potential as new antifungal agents.
