# Phytosterols in Seaweeds: An Overview on Biosynthesis to Biomedical Applications
## 2 Biosynthesis of Phytosterols
### Biosynthesis of Isoprene  
Isoprene is the basic unit of all isoprenoids and terpenoids with a five-carbon functional group [17]. In a eukaryotic cell, the synthesis of isoprenes, namely isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) can be carried out through two unique pathways called mevalonate (MVA) and methylerythntol phosphate (MEP) pathways. All plant species can utilize both these pathways to generate the precursors of isoprenes. In contrast, green macroalgae are found to use the MEP pathway, as they lack the genes involved in the MVA pathway. However, red algae have the potency to synthesize IPP and DMAPP through both these cytosolic- and plastid-relying mechanisms. It is postulated that during endosymbiosis, green algae could have lost machinery from the MVA pathway and evolved with most relying on the MEP pathway for all fundamental aspects of isoprenoid synthesis. Conversely, primary endosymbionts, such as plants and red algae, have retained both MVA and MEP pathways over their evolutions [18]. Most portions of the MVA and MEP pathways transpire in the cytoplasm and plastid, respectively. Interestingly, all the sequential events of the MEP pathway ensue in plastids; however, the genes involved in these processes are encoded by the nuclear genome [19; 20]. Furthermore, the MEP pathway produces both IPP and DMAPP directly, whereas MVA produces only IPP that is followed by isomerization of IPP into DMAPP by IPP isomerase (IPPI). As green algae rely solely on the MEP pathway for isoprenoid synthesis, they have evolved to express chloroplast membranal antiporters to maintain a balanced flux of IPP/DMAPP between plastid and cytosol [21]. Though the MEP pathway produces both these precursors, the ratio of IPP: DMAPP generated through this event varies among plant species.  
The MVA pathway comprises six enzymatic reactions, which commence with acetyl-CoA condensation by acetyl-CoA C-acetyltransferase (ACCT), followed by synthesis of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) by HMG-CoA synthase (HMGS) with subsequent reduction by HMG reductase (HMGR) to form MVA as an intermediate. MVA is then pyrophosphphorylated and decarboxylated in subsequent steps by mevalonic acid (MK), phosphomevalonate (PMK) kinases and mevalonate-5-diphosphate decarboxylase (MPDC), respectively, to form the final isoprene unit, IPP. In the MEP pathway, the final product pyruvate, and intermediate- glyceraldehyde-3-phosphate (G3P), of glycolysis are converted into isoprene via seven successive steps. Pyruvate and G3P are condensed together to produce 1-deoxy-D-xylulose 5-phosphate (DXP) by DXP synthase (DXS), followed by reduction, cytidylation, phosphorylation, dectidylation and final reduction by DXP-reducoisomerase (DXR), 2-C-methyl-derythritol 4-phosphate cytidylylyttransferase (MCT), 4-(cytidine 5\({}^{\prime}\)-diphospho)-2-C-methyl-D-erythritol kinase (CMK), 2-C-methyl- D-erythritol 2-4-cyclodiphosphate synthase (MDS), 4-hydroxy-3-methylbut-2-enyldiphosphate (HMBPP) synthase (HDS) and HMBPP reductase (HDR), respectively, to generate the end isoprene products IPP and DMAPP (Figure 1A).