Transport Engineering Technology for Biotech

Plants synthesize a vast number of specialized small molecules (often referred to as natural products), many of which have large commercial potential. Because of the minute amounts found in natural sources, bio-engineering in microorganisms has emerged as a means for large-scale production of natural products.

Once the complex and highly resource-demanding effort of engineering a new biosynthetic pathway into microorganisms is accomplished, the next challenge is to make the production commercially viable.

Our hypothesis is that efficient export of products from engineered microorganisms into the growth medium will 1) increase yield by preventing autotoxicity and feed-back inhibition and 2) allow cost-efficient purification from the surrounding growth medium, which requires vastly simpler processing compared to purification from cell lysates after breaking the cells open.

Natural products are transported between tissues within plants, which means that exporters of natural products exist in nature. Currently, few approaches have been developed for identification of plant exporter genes, and these are very laborious, biased and low-throughput and thus not amenable for high-throughput identification of plant natural product exporters. In consequence, very few exporters of any plant natural product have been identified to date.

The success of transport engineering technology in bio-engineering approaches will depend upon the availability of an arsenal of exporter proteins with different substrate specificities and appropriate biochemical properties. To fulfill this need, we are generating a state-of-the-art exporter identification platform capable of identifying exporters of plant natural products. Implementation of these exporters in engineered yeast strains will not only enable cost-efficient production, but will also provide the first proof-of-concept for the power of transport engineering in bio-engineering approaches.