New control pathways in synthesis of plant chemical defences

Secondary metabolites: defense and adaptation to the environment

The study analyses the synthesis of saponins, a group of secondary metabolites found in many plants. Saponins defend plants against environmental aggressions (pathogens, herbivores, etc.), by altering membrane permeability, and have importance in pharmaceutical and industrial sectors as antimicrobial, anticancer and haemolytic agents.

Saponins derive from the isoprenoid (terpenoid) biosynthetic pathway, a metabolic route in which the HMGR (3-hydroxy-3-methylglutaryl-CoA reductase) enzyme plays key role. As Professor Narciso Campos mentions, "HMGR was identified four decades ago in mammals, and a few years later in plants and fungi. In the case of humans, it has a key regulatory role in the synthesis of cholesterol, the imbalance of which causes severe abnormalities, such as atherosclerosis. In the case of plants and fungi, the enzyme plays also a crucial role in sterol biosynthesis. Because its biomedical interest, isoprenoid biosynthesis is the subject with the highest number of Nobel Prizes."

A molecular brake in saponin biosynthesis

The new research is focused on the plant Medicago truncatula, a legume used as a model in physiological and molecular studies. When plants detect an external challenge, massive accumulation of saponins is triggered by the phytohormone methyl jasmonate. More precisely, this biochemical signal induces different isoforms of the enzyme HMGR and, subsequently, the synthesis of the defensive saponins. As proposed in the published work, there is brake for this metabolic cascade which was unknown to date: E3 ubiquitin ligase; it negatively regulates HMGR activity and, consequently, saponin synthesis.

"Ubiquitin ligase is a subunit of the protein degradation system ubiquitin-proteasome system. which recognises the molecular target to be degraded. In protein biology, degradative processes are as important as biosynthetic ones. In fact, many human diseases are due to the accumulation of proteins which have not been conveniently degraded," points out Narciso Campos, member of the Research Group Plant Molecular Genetics of UB and the Centre for Research in Agricultural Genomics (CRAG).

A highly complex pathway in plants

Unlike other organisms, plants have a highly complex isoprenoid biosynthetic pathway. To date, around 35,000 isoprenoid compounds, most from plants, have been described. The identified compounds, which are only a part of those present in nature, have an extraordinary biotechnological and industrial potential. Isoprenoids are essential for many plant functions (respiration, photosynthesis, development, cell organization, etc.) and for the plant interaction with the environment (defense, insect attraction, etc.). "Each group of plants has its particular set of isoprenoids," explains Narciso Campos.

Progress in the elucidation of isoprenoid biosynthetic pathway, in plants, opens new paths in the research of cholesterol metabolism. Yeast, mammal and plant HMGR have a bipartite structure formed by the catalytic domain and a membrane domain inserted in the endoplasmic reticulum. Several studies have shown that the expression of the HMGR membrane domain leads to massive accumulation of endoplasmic reticulum membranes. Narciso Campos points out that this has been maintained through evolution and could be related to the control of sterol biosynthesis.