Dai Longhai, Li Jiao, Yang Jiangang, Zhu Yueming, Men Yan, Zeng Yan, Cai Yi, Dong Caixia, Dai Zhubo, Zhang Xueli, Sun Yuanxia
National Engineering Laboratory for Industrial Enzymes, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences , 32 Xiqi Road, Tianjin Airport Economic Area, Tianjin 300308, China.
University of Chinese Academy of Sciences , Beijing 100049, China.
J Agric Food Chem. 2018 Jan 31;66(4):943-949. doi: 10.1021/acs.jafc.7b03907. Epub 2018 Jan 22.
Ginsenosides are the principal bioactive ingredients of Panax ginseng and possess diverse notable pharmacological activities. UDP-glycosyltransferase (UGT)-mediated glycosylation of the C6-OH and C20-OH of protopanaxatriol (PPT) is the prominent biological modification that contributes to the immense structural and functional diversity of PPT-type ginsenosides. In this study, the glycosylation of PPT and PPT-type ginsenosides was achieved using a promiscuous glycosyltransferase (Bs-YjiC) from Bacillus subtilis 168. PPT was selected as the probe for the in vitro glycodiversification of PPT-type ginsenosides using diverse UDP-sugars as sugar donors. Structural analysis of the newly biosynthesized products demonstrated that Bs-YjiC can transfer a glucosyl moiety to the free C3-OH, C6-OH, and C12-OH of PPT. Five PPT-type ginsenosides were biosynthesized, including ginsenoside Rh1 and four unnatural ginsenosides. The present study suggests flexible microbial UGTs play an important role in the enzymatic synthesis of novel ginsenosides.
人参皂苷是人参的主要生物活性成分，具有多种显著的药理活性。原人参三醇（PPT）的C6-OH和C20-OH的UDP-糖基转移酶（UGT）介导的糖基化是导致PPT型人参皂苷巨大结构和功能多样性的主要生物修饰。在本研究中，使用来自枯草芽孢杆菌168的一种多底物糖基转移酶（Bs-YjiC）实现了PPT和PPT型人参皂苷的糖基化。选择PPT作为探针，使用多种UDP-糖作为糖供体，对PPT型人参皂苷进行体外糖基多样化。对新生物合成产物的结构分析表明，Bs-YjiC可以将葡萄糖基部分转移到PPT的游离C3-OH、C6-OH和C12-OH上。生物合成了五种PPT型人参皂苷，包括人参皂苷Rh1和四种非天然人参皂苷。本研究表明，灵活的微生物UGT在新型人参皂苷的酶促合成中起重要作用。
