## 2 Results
### MEP Pathway Genes Are Highly Coexpressed in IPAP Cells of Young Leaves  
The expression of MEP pathway genes was first analyzed using publically available RNA seq data (Table 2). Interestingly, the coexpression network built using DXS2.1 as a bait illustrated the strong coexpression of all available MEP pathway genes. Six of them were found within the first 20 positions of the network with the Pearson correlation coefficient >0.95. DXS2.2 was ranked 64 with a PCC > 0.90 and HDR was not found on the data set. We further analyzed the expression pattern of the eight genes on fully developed _C. roseus_ plants by RT-qPCR. Transcripts of each enzyme were detectable in all tested organs, including young and mature leaves, internodes, flower buds and flowers (Figure 3A-H). Figure 2: Functional characterization of DXS2.2, CMS, CMK and HDR by complementation of _E. coli_ mutant strains. DXS, CMS, CMK-deficient _E. coli_ cells (**A**) or HDR-deficient _E. coli_ cells (**B**) were transformed with constructs expressing the TP-deleted DXS2.2, CMS, CMK or HDR (HDR2 and HDR3 represent two different deletions of the transit peptide), respectively, or with the original pQE30 vector as a control. After recovering the transformed cells on plates supplemented with 1 mM mevalonate (MVA) to rescue the lethal deletion, colonies were replicated on new plates with (+MVA) or without MVA (\(-\)MVA) at 37 \({}^{\circ}\)C for DXS, CMS, CMK (**A**) or on plates containing MVA with Glucose (+Glc) or Arabinose (+Ara) for HDR. \begin{table}
\begin{tabular}{c c c c c c c c c} \hline
**RANK** & **1** & **2** & **8** & **14** & **16** & **20** & **64** & **NF** \\ \hline
**PCC** & **1** & **0,98859** & **0,96838** & **0,96244** & **0,96168** & **0,955751** & **0,921181** & **NF** \\ \hline
**CRA** & & & & & & & & \\
**LOCUS** & **618** & **4910** & **1424** & **7966** & **891** & **4962** & **381** & **2720** \\ \hline
**NAME** & **DXS2.1** & **CMK** & **HDS** & **MECS** & **CMS** & **DXR** & **DXS2.2** & **HDR** \\ \hline
**CRA\_AA** & **22** & **66** & **149** & **40** & **26** & **69** & **9** & \\
**CRA\_AN** & **49** & **65** & **144** & **82** & **33** & **65** & **15** & \\
**CRA\_AM** & **36** & **81** & **161** & **89** & **30** & **92** & **9** & \\
**CRA\_AO** & **34** & **37** & **48** & **27** & **10** & **52** & **16** & \\ \hline
**CRA\_AF** & **221** & **113** & **239** & **87** & **39** & **138** & **45** & \\  
** & **80** & **93** & **1154** & **385** & **136** & **1288** & **30** & \\ \hline \end{tabular}
\end{table} 
Table 2: MEP pathway gene RNA seq coexpression pattern. A _DXS2.1_ coexpression network was drawn using Medicinal Plant Genomics Ressource MPGR RNA seq data [44] showing the clustering of the MEP pathway genes. The codes for the 23 samples and the transcript accession numbers (i.e., cra locus numbers) are from MPGR. See methods for details. An overall coordinated expression pattern of the whole set of genes, except _DXS2.2_, could be observed with a high accumulation of transcripts in young and actively growing aerial organs (young leaves, flowers buds) but also to a lesser extent in roots and flowers, and with lower levels in internode and mature leaves. Such an expression profile also tightly correlates with that of the IDI gene analyzed on the same samples [34] and is in agreement with the high demand of IPP and DMAPP to fulfill the variety of MEP pathway-derived terpenoid metabolisms in these different organs. By contrast, the distribution pattern of _DXS2.2_ transcript distribution was somehow different from _DXS2.1_ with barely detectable transcripts in roots and highest expression in flower buds, suggesting that both isoforms could be involved in different physiological processes. Subsequently, we performed in situ RNA hybridization of _DXS2.2_, _CMS_, _CMK_ and _HDR_ transcripts on serial sections of young developing leaves, with _DXS2.1_, _DXR_, _MECS_ and _HDS_ as controls (Figure 4).