Phylogenetic analysis and functional characterization of norcoclaurine synthase involved in benzylisoquinoline alkaloids biosynthesis in Stephania tetrandra
Artikel i vetenskaplig tidskrift, 2024
Benzylisoquinoline alkaloids (BIAs) are a class of secondary metabolites that possess diverse pharmaceutical properties and are exclusively accumulated in specific plant genera. The Pictet–Spengler condensation, catalyzed by norcoclaurine synthase (NCS), represents a key enzymatic reaction in the biosynthetic pathway of BIAs. While NCS genes have been identified in several plant families such as Papaveraceae, Berberidaceae, and Ranunculaceae, no NCS genes have been reported in Menispermaceae, which is another genus known to accumulate BIAs. Here, NCSs were isolated and functionally characterized from the Menispermaceae family plant Stephania tetrandra. In vitro enzyme assay identified two functional StNCSs which could catalyze the formation of (S)-norcoclaurine. These functionally characterized genes were then integrated into engineered yeast to enable the production of norcoclaurine. Phylogenetic analysis of the NCS enzymes revealed that the StNCSs predominantly clustered into two clades. The functional StNCSs clustered with known NCSs, highlighting the presence of a specific NCS catalytic domain. This study not only provides additional genetic components for the synthetic biology-based production of BIAs in yeast but also contributes to the understanding of the phylogenetic relationships and structure–function relationship of NCS genes involved in the origin and production of BIAs.
norcoclaurine synthase
benzylisoquinoline alkaloids
Pictet–Spengler condensation
phylogenetic analysis
Menispermaceae
Författare
Xinyi Li
China Academy of Chinese Medical Sciences
Chengdu University of Traditional Chinese Medicine
Qishuang Li
China Academy of Chinese Medical Sciences
China Pharmaceutical University
Xiang Jiao
Chalmers, Life sciences, Systembiologi
Hao Tang
Nanjing University of Traditional Chinese Medicine
China Academy of Chinese Medical Sciences
Yatian Cheng
China Academy of Chinese Medical Sciences
Ying Ma
China Academy of Chinese Medical Sciences
Guanghong Cui
China Academy of Chinese Medical Sciences
Jinfu Tang
China Academy of Chinese Medical Sciences
Yun Chen
Chalmers, Life sciences, Systembiologi
Juan Guo
China Academy of Chinese Medical Sciences
Luqi Huang
China Academy of Chinese Medical Sciences
Journal of Cellular Physiology
0021-9541 (ISSN) 1097-4652 (eISSN)
Vol. 239 10 e31065Microbial synthesis of medicinal natural products
STINT (CH2019-8258), 2020-04-01 -- 2023-12-31.
Ämneskategorier
Biokemi och molekylärbiologi
Organisk kemi
DOI
10.1002/jcp.31065
PubMed
37357496