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Research on the mechanism of synthesis of chicory acid, the active ingredient of Echinacea purpurea

By | 19/03/2021 03:22

On March 10, Zhang Yang's team, a researcher in the College of Life Sciences at Sichuan University, published a research paper online in Nature Communications, which completely analyzed the biosynthetic pathway of chicory acid, the main active ingredient

Research on the mechanism of synthesis of chicory

 

Echinacea is a medicinal plant native to North America and was originally used by the Indians of the Great Plains region of North America to treat snake bites, coughs and colds. Echinacea had a medicinal history of more than 400 years before the Europeans set foot in the New World, and was later introduced to Europe and used to this day. At present, Echinacea has become one of the most widely used medicinal plants in Europe and America. Modern scientific research has shown that Echinacea has immunomodulatory effects and can shorten the cold and flu cycle. 2019 sales of Echinacea in the mainstream U.S. market reached $120 million, and in the first half of 2020 sales have surged, with annual sales expected to exceed $200 million.

Chicory acid is the main component of Echinacea, with levels up to 4% of dry weight. Although several studies in recent years have found that chicory acid has a variety of biological activities, such as HIV integrase inhibition, anti-inflammatory, antioxidant, anti-virus, obesity inhibition, anti-tumor, etc., however, its biosynthetic pathway has been unclear.

On March 10, Zhang Yang's team, a researcher from the College of Life Sciences of Sichuan University, published a research paper online in Nature Communications, which completely analyzed the biosynthetic pathway of chicory acid, the main active ingredient in Echinacea purpurea.

In order to explore the biosynthetic pathway of chicory acid and lay the foundation for subsequent synthetic biology research, the team combined traditional biochemical methods and modern plant molecular biology research tools, firstly, successfully established an in vitro enzyme reaction system, and screened the candidate structural genes through enzyme isolation and purification, combined with protein profiling. Secondly, the functions of the candidate genes were confirmed by molecular cloning, heterologous expression, in vitro enzyme activity verification, in vivo overexpression and silencing verification, and the related properties of the enzymes were investigated in the process. Finally, the biosynthetic pathway of chicoric acid in Echinacea was successfully resolved, and the heterologous construct was successfully realized in tobacco.

The biosynthesis of chicoric acid involves the two known families of acyltransferases BAHD and SCPL in plants. in the cytoplasm, two BAHD family members EpHTT and EpHQT catalyze the reaction of caffeoyl coenzyme A with tartaric acid and quinic acid to produce caffeoyl tartaric acid and chlorogenic acid, respectively. the two products enter the vesicles and are catalyzed by EpCAS, a member of SCPL family, to produce chicoric acid and quinic acid. While the identified functional SCPL-like acyltransferases mainly use 1-O-β-glucoside as the acyl donor, the EpCAS acyl donor changed to chlorogenic acid, a finding that changed the perception of the SCPL family acyltransferases. Meanwhile, by comparing with some species known to be able to synthesize chicory acid, the researchers found that this newly identified chicory acid synthesis pathway is unique to Echinacea, suggesting that the chicory acid synthesis pathway may have evolved convergently in different species.

This study is an important advance in the field of medicinal plant research and provides new research ideas for the elucidation of biosynthetic pathways of medicinal components. All three reviewers gave high evaluations to this work. One of the reviewers specifically noted, "This study shows that solid biochemical and enzymatic research techniques remain the most important way to discover original compound synthesis pathways in non-model plants, as opposed to the current conventional thinking that relies on genome resolution and co-expression analysis."

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