Divergent contribution of the MVA and MEP pathways to the formation of polyprenols and dolichols in Arabidopsis

Abstract

Isoprenoids, including dolichols (Dols) and polyprenols (Prens), are ubiquitous components of eukaryotic cells. In plant cells there are two pathways that produce precursors utilized for isoprenoid biosynthesis: the mevalonate (MVA) pathway and the methylerythritol phosphate (MEP) pathway. In this work the contribution of these two pathways to the biosynthesis of Prens and Dols was addressed using an in planta experimental model. Treatment of plants with pathway-specific inhibitors and analysis of the effects of various light conditions indicated distinct biosynthetic origin of Prens and Dols. Feeding with deuteriated, pathway-specific precursors revealed that Dols, present in leaves and roots, were derived from both MEP and MVA pathways and their relative contributions were modulated in response to precursor availability. In contrast, Prens, present in leaves, were almost exclusively synthesized via the MEP pathway. Furthermore, results obtained using a newly introduced here ‘competitive’ labeling method, designed so as to neutralize the imbalance of metabolic flow resulting from feeding with a single pathway-specific precursor, suggest that under these experimental conditions one fraction of Prens and Dols is synthesized solely from endogenous precursors (deoxyxylulose or mevalonate), while the other fraction is synthesized concomitantly from endogenous and exogenous precursors. Additionally, this report describes a novel methodology for quantitative separation of 2H and 13C distributions observed for isotopologues of metabolically labeled isoprenoids. Collectively, these in planta results show that Dol biosynthesis, which uses both pathways, is significantly modulated depending on pathway productivity, while Prens are consistently derived from the MEP pathway.

Integrative metabolomic and transcriptomic reveals potential mechanism for promotion of ginsenoside synthesis in Panax ginseng leaves under different light intensities

“…Therefore, high light intensity not only enhanced the synthesis of triterpenoid saponins but also promoted the accumulation of other terpenoid components in P. ginseng leaves. Terpenoid metabolism begins with acetyl coenzyme A, which is further synthesized through the mevalonate (MVA) pathway and methylerythritol-4-phosphate (MEP) pathways (Lipko et al, 2023). As shown in the transcriptome data, the expression levels of HMGR, FPS, and other genes were upregulated under high light intensity.…”

Hydroxamate-Containing Bisphosphonates as Fosmidomycin Analogues: Design, Synthesis, and Proherbicide Activity

“…7,8 The two pathways exist independently and cannot compensate for one another, allowing the seven key enzymes in the MEP pathway to be potential targets for new bactericide and herbicide development. 9,10 The second enzyme, 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR), which catalyzes transformation of the substrate 1-deoxy-D-xylulose 5-phosphate (DXP) to MEP (Figure 1), is the most studied target for the bactericide development thus far. 11−13 The research on herbicide discovery with DXR as a mode of action, however, is rather rare.…”

“…In plants, the MVA pathway primarily operates in the cytoplasm, responsible for the biosynthesis of terpenoids such as squalene and phytosterol starting with acetyl CoA, while the MEP pathway occurs predominantly in plastids for biosynthesis of the terpenoids such as phytol and carotene from pyruvate and glyceraldehyde 3-phosphonate (GAP) (Figure ). , The two pathways exist independently and cannot compensate for one another, allowing the seven key enzymes in the MEP pathway to be potential targets for new bactericide and herbicide development. , The second enzyme, 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR), which catalyzes transformation of the substrate 1-deoxy-D-xylulose 5-phosphate (DXP) to MEP (Figure ), is the most studied target for the bactericide development thus far. − The research on herbicide discovery with DXR as a mode of action, however, is rather rare. Considering the importance of new modes of action toward sustainable agriculture, developing novel herbicidal lead compounds targeting the DXR enzyme would be of great significance.…”

Design, Synthesis and Bioactivity Evaluation of Heterocycle-Containing Mono- and Bisphosphonic Acid Compounds

“…The products of the MEP pathway, isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), are crucial precursors for the synthesis of various isoprenoids [4]. For example, plants utilize IPP and DMAPP produced via the MEP pathway to synthesize phytol, β-carotene and other substances that are essential to the photosynthesis process and physiological regulation (Figure 1) [5]. The second enzyme in this pathway, 1-deoxy-D-xylulose 5-phosphate reductoisomerase, shortly named DXR and also known as IspC, which catalyzes the isomerization and reduction of 1-deoxy-D-xylulose 5-phosphate (DXP) to produce MEP [6], is the most encouraging target for the development of novel antibacterial and antimalarial drugs because two naturally occurring products, fosmidomycin (FOS) and FR900098 (FR), have been found active in targeting this enzyme, and the inhibition mechanism has been well documented [7,8].…”