Plant Metabolism and Engineering – From Cars to Mars:
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 the IPK in Gatersleben is interested in 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.
The D’Auria lab is also interested in functional metabolomics. As an example, we have 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 right depicts normal Arabidopsis plants while the plant to the right was engineered to not only over-produce anthocyanins, but to modify the actual normal end-product into accumulating an intermediate anthocyanin to high concentrations.
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 re-engineering these pathways in plants and micro-organisms and optimizing their production. The D'Auria labs efforts are focused on understanding tropane alkaloid and hypericin/hyperforin production via multiple methods. These include MALDI imaging 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.
Hypericum research – connecting transcriptomics to metabolomics
Hypericum perforatum, also known as Saint John’s Wort (SJW), is part of a genus including over 400 species distributed all around the world and characterized by great diversity (Crockett and Robson 2012). Saint John’s Wort is a popular medicinal plant that produces bio active compounds and is recognized for its mild antidepressant properties (Schallau et al 2010; Galla et al 2011; Rizzo 2016). Hypericin is one of the many bioactive compounds produced by SJW that got the attention of the scientific community thanks to its potential use in the treatment of the Alzheimer disease (Sgarbossa et al 2008; Bramanti et al 2010) and to its applications in cancer photodynamic therapy (Garg et al 2010, 2012; Dudek-Peric 2015). Despite the long effort in the study of hypericin production, this biosynthetic pathway remains mostly uncharacterized.
Dr. Paride Rizzo, a postdoc of the D’Auria lab, is interested in the developmental biology of SJW. His research lead to the identification of contrasting phenotypes of glanded and glandless tissues (G-/G+ PT) in the flowers of H. perforatum (Rizzo et al 2019).
We compare these phenotypes to identify the main metabolic and transcriptomic differences between glanded and glandless tissues. Using this combination of genetic and metabolic subtraction, we identify candidate genes for the biosynthesis of hypericin and for the differentiation of dark glands.
Currently the MD group is implementing a pipeline for the test of such genes using expression assays in microorganisms as well as in plants.
Considering the high metabolic cost of synthesizing hypericin and producing glands to keep it compartmentalized, we are curious about the ecological and evolutionary advantages of its biosynthesis. With this in mind, we explore the metabolic and genomic diversity of H. perforatum and combine the phylogenesis of this species with its hypericin production patterns in order to understand if the trait of dark glands formation has a geographical structure and if it is going to be lost in evolution.
While we characterize several genotypes of the species perforatum, we are also addressing the interspecific diversity of the genus Hypericum thanks to a germplasm collection that we are currently growing in our lab.
Our research is embedded in a network of partners including: IPB Halle, Halle University, University of Braunschweig, University of Saskatchewan and University of Heidelberg.
With our research on Hypericum we want to generate new scientific results that will be useful for the implementation of future applications in the pharmaceutical industry and in medical research.