The D’Auria Lab Plant Metabolic Engineering: From Cars to Mars TTU Center for Chemical Biology A green solution to the production of valuable organic compounds would be a boon to the environment, the economy, and to the advancement of our knowledge of metabolic pathways. Plants can be a tremendous and valuable resource for the production of complex compounds that would normally require vast resources and involve environmentally damaging chemicals when produced by traditional methods. The D’Auria lab at Texas Tech University is focused on engineering value added traits into plants and micro-organisms to be solutions for problems ranging from biofuels to space exploration. Currently, the research team led by Dr. D’Auria is focused on the engineering of the tropane alkaloid biosynthetic pathway for use as pharmaceutical compound production. Several tropane alkaloids are listed by the World Health Organization as the most essential medicines needed for basic health care. Other ongoing studies are focused on identification of gene controlling elements (promotors) involved in tissue specific expression. As an example, the figure on the right shows a plant construct where a seed specific promotor was identified. These control elements will be essential for targeted metabolic gene expression. In this case, genes encoding enzymes to modify seed oils for biofuels are targeted to the highly enriched oil producing seeds. Jirschitzka J, Mattern D, Gershenzon J, D’Auria JC, Learning from nature: New approaches to the metabolite engineering of plant defense pathways. Current Opinion in Biotechnology 24(2): 320-328 (2013) In another study, the D’Auria group identified key enzymes for modifying anthocyanins, the compounds responsible for the red to purple shades of colors in leaves and flowers. Anthocyanins are ingredients in ‘super foods’ because of their anti-oxidant and cancer fighting qualities. The figure to the left depicts normal Arabidopsis plants while the plant to the right was engineered to not only over-produce anthocyanins, but to modify the actual normal profile to a more valuable compound. D’Auria JC, Reichelt M, Luck K, Svatos A, Gershenzon J, Identification and characterization of the BAHD acyltransferase malonyl CoA: Anthocyanidin 5-O-glucoside-6''-O-malonyltransferase (At5MAT) in Arabidopsis thaliana. FEBS Letters 581 (5): 872-878 (2007) There are no petrochemicals in space. This one simple fact precludes making pharmaceuticals and other complex organic molecules on a manned mission to Mars or to the moon. Bringing up a pharmacopeia of relevant compounds would be weight prohibitive when there are better solutions. The D’Auria lab is interested in modifying the plants that would be grown in space for food and oxygen so that they would also produce the astronaut’s medicines. The first steps are fully understanding the pathways involved in the process of biosynthesizing these essential medicinal compounds. The next steps will include reengineering these pathways in plants and micro-organisms and optimizing their production. In the figure below, you can see the D’Auria labs efforts in the first stages of understanding tropane alkaloid production via multiple methods. These include MALDI imagining of where pharmaceuticals accumulate, protein crystallography and modeling of key biosynthetic enzymes as well as their localization via immunohistochemistry. Mixing and matching enzymes from different plant families wield broaden the possibilities for metabolic engineering of novel medicinal compounds. 1. Schmidt G, Jirschitzka J, Porta T, Reichelt M, Luck K, Pardo-Torre J, Dolke F, Varesio E, Hopfgartner G, Gershenzon J, D’Auria JC. The last step in cocaine biosynthesis is catalyzed by a BAHD acyltransferase. Plant Physiology 16(1), 89-101 (2015) 2. Jirschitzka J, Schmidt GW, Reichelt M, Schneider B, Gershenzon J, D’Auria JC, Plant tropane alkaloid biosynthesis evolved independently in the Solanaceae and Erythroxylaceae. Proceedings of the National Academy of Sciences 109 (26): 10304-10309 (2012)