Methylerythritol 4-phosphate (MEP) pathway metabolic regulation

Abstract

Covering: up to February 2014. The methylerythritol 4-phosphate (MEP) pathway is the recently discovered source of isoprenoid precursors isopentenyl diphosphate (IDP) and dimethylallyl diphosphate (DMADP) in most bacteria, some eukaryotic parasites, and the plastids of plant cells. The precursors lead to the formation of various isoprenoids having diverse roles in different biological processes. Some isoprenoids have important commercial uses. Isoprene, which is made in surprising abundance by some trees, plays a significant role in atmospheric chemistry. The genetic regulation of this pathway has been discussed but information about metabolic regulation is just now becoming available. This review covers metabolic regulation of the MEP pathway starting from the inputs of carbon, ATP, and reducing power. A number of different regulatory mechanisms involving intermediate metabolites and/or enzymes are discussed. Some recent data indicate that methylerythritol cyclodiphosphate (MEcDP), the fifth intermediate of this pathway, is a key metabolite. It has been found to play diverse roles in regulation within the pathway as well as coordinating other biological processes by acting as a stress regulator in bacteria and possibly a retrograde signal from plastids to the nucleus in plants. In this review we focus on the role of the MEP pathway in photosynthetic leaves during isoprene emission and more generally the metabolic regulation of the MEP pathway in both plants and bacteria.

Contribution of understorey vegetation and soil processes to boreal forest isoprenoid exchange

“…Earlier studies have also suggested that litter and decomposers are important isoprenoid sources (Hayward et al, 2001;Asensio et al, 2007Asensio et al, , 2008Isidorov et al, 2010;Insam and Seewald, 2010;Aaltonen et al, 2013;Greenberg et al, 2012;Faiola et al, 2014). Monoterpenes can be produced simultaneously by MEP pathways in plastids and by MVK pathways in cytoplasm, and at least some fungi and bacteria are capable of activating the MEP pathway (Rohmer et al, 1993(Rohmer et al, , 1996Eisenreich et al, 1998;Walter et al, 2000;Banerjee and Sharkey, 2014). Soil can also absorb 80 % of litter-produced VOCs (Ramirez et al, 2010), when soil and litter samples from a Pinus taeda stand on a loamy sand soil (pH 3.6, 50 % of the water holding capacity) were studied in a laboratory.…”

Discovery of a Unique Clp Component, ClpF, in Chloroplasts: A Proposed Binary ClpF-ClpS1 Adaptor Complex Functions in Substrate Recognition and Delivery

“…Considering all data, HDS is likely degraded by the Clp system, but multiple factors regulate its protein level and activity. It was noted that HDS, together with HDR immediately downstream of HDS, constitutes the light-regulated portion of the MEP pathway (Banerjee and Sharkey, 2014). Future studies should investigate the posttranslational mechanisms governing the stability of this candidate Clp target.…”

“…The 2-C-methyl-D-erythritol 4-phosphate/1-deoxy-D-xylulose 5-phosphate (MEP) pathway provides the isoprenoids in plastids needed for the biosynthesis of carotenoids and the phytyl moiety of chlorophylls, quinines, and tocopherols; this pathway is essential and tightly regulated at both the transcriptional and posttranscriptional levels (Banerjee and Sharkey, 2014;Rodríguez-Concepción and Boronat, 2015). The MEP pathway enzyme 4-hydroxy-3-methylbutyl diphosphate synthase (HDS) was found to be strongly upregulated (2-to 10-fold) in clpc1, clpt1 clpt2 double mutants, and ClpPR mutants Zybailov et al, 2009;Nishimura et al, 2013).…”

Metabolic Engineering of Microorganisms for the Production of Natural Compounds

“…[26] For the past 50 years, most of the regulatory mechanisms of the MEV pathway have been unraveled while those of the DXP pathway have only just begun to be under investigation, leaving much information on the latter pathway mechanisms unavailable. [29] Of the two pathways, the DXP pathway is more energetically balanced and efficient than the MEV pathway. [30] However, in the case of terpenoids production Enzymes that the corresponding genes encode are as follows: dxr, 1-deoxy-D-xylulose 5-phosphate reductoisomerase; dxs, 1-deoxy-D-xylulose 5-phosphate synthase; gapA, glyceraldehyde 3-phosphate dehydrogenase; idi, isopentenyl pyrophosphate isomerase; ispD, 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase; ispE, 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase; ispF, 4-diphosphocytidyl-2-Cmethyl-D-erythritol kinase; ispG, 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase; ispH, 4-hydroxy-3-methylbut-2-enyl diphosphate reductase; pps, phosphoenolpyruvate synthase.…”