Isoprenoids artemisinin

Besides their essential roles in nature, isoprenoids are of commercial importance in industry. Some isoprenoids have been used as flavors, fragrances, spices, and food additives, while many are used as pharmaceuticals to treat an array of human diseases, such as cancer (Taxol), malaria (artemisinin), and HIV (coumarins). In contrast to the huge market demand, isoprenoids are present only in low abundance in their host organisms. Thus, isolation of the required isoprenoids consumes a large quantity of natural resources. Furthermore, owing to their structural complexity, total chemical synthesis is often not commercially feasible. For these reasons, metabolic engineering may provide an alternative to produce these valuable isoprenoids [88,89]. 

The IPP monomer serves as the universal building block for the production of all isoprenoids, including artemisinine, carotenoids, and Taxol. Thus, an engineered strain with high potential for generating IPP provides a platform for production of a variety of complex isoprenoids. The presence of two IPP synthesis pathways allows two approaches for engineering such strains. One is to introduce a heterozygous pathway and the other is to alter or modify the native pathway. Both approaches have been accomplished in E. coli. 

IPP, and/or DMAPP) can also cause sharp growth inhibition, which can be alleviated by the coexpression of a codon-optimized terpene synthase from the artemisinin pathway [27, 28]. Additionally, the production of lycopene was increased in E. coli by assembling a synthetic mevalonate pathway, which included mevalonate kinase and 5-diphosphomevalonate decarboxylase from yeast, human 5-phosphomevalonate kinase, and E. coli IPP/DMAPP isomerase [29]. Finally, studies on isoprenoid production in S. cerevisiae mainly focused on the mevalonate pathway. For example, Shiba et al. successfully amplified the flux to mevalonate in S. cerevisiae by overexpressing acetyl-CoA synthetase from Salmonella enterica and acetaldehyde dehydrogenase [30]. 

A variety of microorganisms produce hydrocarbons or their precursors. For example, bacteria, primarily Bacillus, produce isoprene (Kuzma et al. 1995). Iso-prenoid compounds are common in nature, mostly in plants, and find application in human life in the production of pharmaceuticals, flavours, fragrances and pigments (Walsh 2007). Due to interest in these applications, strains of E. coli and S. cerevisiae have been established for the overproduction of certain isoprenoids. One instance is artemisinic acid, a precursor to artemisinin and an antimalaria drug... 

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