Patricia León - Understanding the regulation and possible manipulation of the limiting enzymes of the MEP pathway required for the synthesis of central molecules in plants

The methylerythritol 4-phosphate (MEP) pathway is of paramount importance for generating plastidial isoprenoids. These compounds have essential biological functions in primary metabolism, regulation of plant growth, biotic and abiotic stresses responses and retrograde signals. Thus the MEP pathway is of special interest for manipulation of diversity of isoprenoids. The MEP pathway operates through seven enzymatic steps to synthesize IPP and DMAPP, the two basic blocks of all isoprenoids. Experimental evidence supports the idea that the first, second and last enzymes of the patway (DXS, DXR and HDR) act as a major flux-controling steps of the pathway. These enzymes are potential targets for manipulation of this route but this also depends on a deep understanding of the regulation of the expression and accumulation of these proteins.

Our group has analyzed the regulation of the genes and proteins of this pathway at the transcripctional and posttranscriptional levels. At the transcriptional level we demonstrated that light, one of the most important signals for plant, acts as a major regulator of the expression of the MEP pathway genes. The molecular mechanism of this regulation involves the participation of known light modulators that participate in a particular manner for each gene, exemplify the complexity of the coregulation of the MEP pathway genes. We have also found other signals including circadian rhythm and plastid development that modulate some of the genes in the pathway.

At the protein level we have found a major regulation of the protein stability for the DXS1 enzyme, the first enzyme of the pathway and we demonstrated that this regulation is maintained in evolution.

We have also explo red the manipulation of the limiting enzymes of this pathway by direct transformation of the genes encoding for these enzymes in tobacco chloroplasts. Our findings show that manipulation of the HDR enzyme of the pathway but not DXS1 impact in the synthesis of final products derived from this pathway. These findings also demonstrated the central role that posttranscriptional regulation plays for the DXS enzyme.