A3. Isoprenoidi biosünteesi raja tehnika

Isoprenoidid on kõige mitmekesisemad vabalt elavate organismide poolt toodetavad metaboliidid. Taimed toodavad eriti suurel hulgal isoprenoide, alates fotosünteesiks vajalikest komponentidest, mitmekesiste ebapüsivate fütohormoonideni, mis on olulised taime suhtlemisel keskkonnaga. Neil biokemikaalidel on suur farmatseutiline ja tööstuslik tähtsus. Vaatamata nende struktuursele mitmekesisusele on kõik isoprenoidid saadud samast C5 elemendist.

  Plants retain and actively use two distinct pathways for the production of these building units in two separate cellular compartments: the cytoplasmic MVA pathway and the plastidial MEP pathway (12). Bioengineering of isoprenoids, as well as functional characterization of downstream genes have been hindered by limited substrate pools. Group 4 has initiated a project aiming to increase the carbon flux for biosynthesis of isoprenoid building units in plants. Unlike the conventional approach of overexpressing genes encoding rate‐ limiting enzymes, we are enhancing the efficiency of these pathways via formation of artificial metabolomes, which are enzyme complexes arranged in a spatially designed manner that allow substrate channeling. This concept has been demonstrated in prokaryotes, and recently also in yeast and mammalian cells (13, 14). Since plants are the host of many valuable isoprenoids, we will first establish plant expression platforms with increased carbon flux for the production of isoprenoid building units. These platforms will be used for further engineering to increase production of specific isoprenoids. As a next step we aim to transfer the essential pathways of isoprenoid biosynthesis to various organisms for higher yield and ease of production. The synthetic biology efforts of group 4 will be complemented with downstream chemical modification steps by group 6. The appropriate biosynthetic, semi‐biosynthetic, synthetic (including organocatalytic and other green chemistry methods) will be developed to provide streamlined solutions for chemical production of various isoprenoids.