Identification of regulatory enzymes is fundamental for engineering metabolic pathways such as the isoprenoid one. All too often, investigation of gene expression remains the major trend in unraveling regulation mechanisms of the isoprenoid cytosolic mevalonate and the plastid-localized methylerythritol phosphate metabolic pathways. But such metabolic regulatory enzymes are frequently multilevel-regulated, especially at a post-translational level. A prominent example is the endoplasmic reticulum-bound 3-hydroxy-3-methylglutaryl coenzyme A reductase catalyzing the synthesis of mevalonic acid. Despite the discovery and the intense efforts made to understand regulation of the methylerythritol phosphate pathway, this enzyme remains a leading player in the regulation of the whole isoprenoid pathway. Strict correlation between this enzyme's gene expression, protein level and enzyme activity is not observed, thus confirming multilevel-regulation. In this context, besides post-translational modifications of proteins, we have to consider feedback of metabolic flow and allosteric regulation, alternative protein structures, targeted proteolysis and/or redox regulation. Such multilevel-regulation processes deliver a range of benefits including rapid response to environmental and physiological challenges or metabolic fluctuations. This review specially emphasizes essential functions of these post-translational events that permit the close regulation of key enzymes involved in plant isoprenoid precursor biosynthesis.
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