## 3 Terpene Compounds
### 1-Deoxyxylulose-5-phosphate Synthae (DXS)  
DXS is considered a major enzyme in the first stage of the MEP pathway of terpenoid biosynthesis, and it is an important rate-determining enzyme in some plant species [66; 67; 68]. There is an extremely conserved thiamine phosphate binding domain with DXS enzymes. Two distinct types of DXS genes have been identified based on their sequence properties and expression pattern: one type (type I) that is constitutively expressed in photosynthetic and floral tissues and is likely involved in the supply of substrate for primary isoprenoids such as carotenoids and phytol, and a second type (type II) that appears to be involved in the supply of substrate for specialized terpenoids [69; 62]. The cDNA cloning and functional recognition of three DXS-encoding genes were reported in Norway spruce (_Pica abies_) [70] (Table 1). The limited protein information for DXS was dependent on the species with different cDNA sequences; the mass of protein was about 70-80 kDa [71; 72; 73], and no additional data were obtained about the structure of the enzyme.  
Hydroxy-3-methylbut-2-enyl Diphosphate Synthae (HDS)/4-Hydroxy-3-methylbut-2-enyl Diphosphate Reductase (HDR)  
The production of terpenoids with more than five carbons needs a plentiful supply of isopentenyl diphosphate (IPP) and its more reactive, electrophilic isomer DMAPP. The enzyme HDS, also known as isoprenoid synthesis G (IspG), first transforms methyleryth-thiritol cyclodiphosphate in a two-electron reduction to 4-hydroxy-3-methylbut-2-enyl diphosphate (HMBPP) in the last two stages of the MEP pathway. In the final branching stage, HDR, also known as isoprenoid synthesis H (IspH), converts HMBPP to a mixture of IPP and DMAPP in a 5 to 6:1 ratio [74; 75; 76]. In plants, IPP/DMAPP isomerase (IDI) have been found in mitochondria, plastids, and cytosol by examination of enhanced green fluorescent protein fusions [77]. As a result, IPP isomerization appears to be less significant in plastids when the MEP route produces both C5 building blocks (DMAPP and IPP). However, plastidial IPP isomerase activity may be required to provide an optimum ratio of IPP and DMAPP for downstream condensation processes and to supply precursors for potential transport to the cytosol. However, it is different for the last enzyme IDI in MVA pathway, and it has been proven to play an essential role in terpene synthesis [78], such as farnesene [79], and so on. This is because the DMAPP can only produce from the IPP catalyzed with IDI in the MVA pathway.  
For the application of the MEP pathway (Table 1), overexpression of these main genes such as DXS, DXR, and IDI significantly increased metabolites yields [80; 81; 82; 83; 84]. The production of heterologous pathway genes is another option for ensuring increased precursor supply. The expression of a synthetic amorphadiene synthase gene was engineered with the mevalonate isoprenoid pathway from _Saccharomyces cerevisiae_ in _Escherichia coli_[85]. Amorphadiene, the sesquiterpene olefin precursor of artemisinin, has up to 24 g cryophyllene equivalent/mL concentrations. Several subsequent investigations revealed that heterologous pathway gene expression in _Escherichia coli_ has a beneficial effect on precursor synthesis [86; 87; 88; 89]. The introduction of the _Escherichia coli_ MEP pathway into yeast, on the other hand, has not been as effective. This is especially important since the last two enzymes of the MEP pathway, IspG and IspH, which contain iron-sulfur clusters and therefore need extra redox partners, appear to be the primary bottlenecks because they cannot be produced in yeast in a soluble form [90].