Full Biosynthetic Pathway of Astragalus Saponin Astragaloside Elucidated: Six Enzymes Identified

The entire process by which astragalosides, the key components of astragalus (Astragalus membranaceus), a medicinal herb used for more than 2,000 years, are made inside the plant has been uncovered. Researchers at the Kunming Institute of Botany, Chinese Academy of Sciences, and Chengdu University of Traditional Chinese Medicine assembled a new chromosome-level genome of astragalus, used it to elucidate the whole biosynthetic pathway, and reported the work in Nature Plants.

Six enzymes found in a gene cluster

The researchers first found two tailoring enzymes essential for astragaloside synthesis, and used them as clues to identify a triterpenoid biosynthetic gene cluster. The pathway is structured so that selective hydroxylation, epoxidation and sugar attachment occur in sequence, involving three cytochrome P450 enzymes, one 2-oxoglutarate-dependent oxidase (2-ODD) and two glycosyltransferases. When these genes were introduced into Nicotiana benthamiana, a relative of tobacco, astragaloside IV was produced.

Securing a stable supply of raw material has been cited as a challenge for astragalosides. With the pathway in hand, there is now a basis for designing production methods that do not depend on cultivation, and the researchers said it also broadens understanding of the diversity of plant terpene gene clusters.

However, this achievement is at the stage of showing the pathway and reproducing it in an experimental plant, and it did not address production yield or economics. It is also not a study that tested the effects of astragalosides in people.