Centre of Excellence In Molecular Cell Engineering

A3.

A3. Engineering the isoprenoid biosynthesis pathway

Isoprenoids are the most diverse metabolites produced by all freeliving organisms. Plants produce a particularly large number of isoprenoids, ranging from components essential for photosynthesis, phytohormones for normal development to diverse volatile compounds that serve specialized roles in plant communication with the environment (11). These biochemicals have great pharmaceutical and industrial value. Despite their structural diversity, all isoprenoids are derived from the same C5 building units. 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 ratelimiting 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, semibiosynthetic, synthetic (including organocatalytic and other green chemistry methods) will be developed to provide streamlined solutions for chemical production of various isoprenoids. 

Contact:

Institute of Technology
University of Tartu
Nooruse 1
Tartu 50411
Estonia
Location

Tanel Tenson
Professor, PI
Tanel.Tenson@ut.ee
+372 737 4844