Complete biosynthesis of the clinical agent escin Ia
Abstract
Abstract Escin Ia is a barrigenol-type triterpenoid specific to Aesculus seeds and is widely utilized in clinical practice for the treatment of cerebral edema, swelling, and venous insufficiency. Here, we fully elucidated its biosynthetic pathway by identifying ten previously uncharacterized enzymes from Aesculus chinensis . AcCYP716BX1/2 catalyze the C-22α and C-28 hydroxylation of the β-amyrin scaffold, and AcCYP714E67 mediates the C-24 hydroxylation to produce protoaescigenin. Sequential glycosylation at the 2’- O and 4’- O positions is catalyzed by AcUGT94AK1/3/6 and AcUGT87AZ3, respectively, forming aesculuside B. AcCCL3 catalyzes the formation of tigloyl-CoA, and AcBAHD13/17 catalyze the C-21β tigloylation of aesculuside B to yield desacetylescin Ia. These enzymes significantly broaden the catalytic versatility of their respective gene families. Finally, we successfully reconstructed the complete pathway in Nicotiana benthamiana , enabling the heterologous production of escin Ia. This work fully elucidates the biosynthesis of escin Ia and establishes a foundation for the green production of barrigenol-type triterpenoid saponins.
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Authors: Huihua Wan, Mofan Zhang, Ranran Gao, Xuehua Xie, Xiangxiao Meng, Songchun Guan, Weiqiang Chen, Xue Cao, Wei Yang, Hui Yao, Chen Qin, YinDi Zhu, Yi Zhang, Zhaohua Shi, Xiang Chen, Lichun Ye, 高慧媛, Shilin Chen, Zhichao Xu, Wei Sun
Institutions: Sun Yat-sen University, Chinese Academy of Medical Sciences & Peking Union Medical College, Chengdu University of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wenzhou Medical University, Tianjin University of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Wuhan Ship Development & Design Institute, Northeast Forestry University, State Forestry and Grassland Administration, China Academy of Chinese Medical Sciences