Person

Nicolas Thilo Wirth
Ph.D. Student

Enthusiast of microbial metabolic engineering and synthetic biology and excited to work at the front of a dawning biotechnological era.


Research

One in four of all molecules currently licensed as pharmaceutical drugs contains fluorine. Its introduction into biologically-active molecules can dramatically modify a number of parameters, e.g. hydrophobicity, binding to a target receptor or enzyme, transport within an organism or metabolic stability. The chemical reactions used to selectively attach F to organic molecules are often challenging to perform due to the high reactivity and toxicity of the reagents involved, thus limiting the substrate scope. Furthermore, all current processes for fluorination rely on chemical synthesis. Nature has not found any biological role for this element aside from its rare occurrence within a handful of biogenic compounds. One reason for the virtual absence of fluorinated compounds in biological systems is that F, being the most electronegative of all elements in the periodic table, is extremely reactive and its bond with carbon (C―F) is highly polarized and extraordinarily strong (i.e. beyond the catalytic scope of most enzymes). On the other hand, these chemical properties confer F a prominent role within the structure of so many commercial compounds. The main goal of my Ph.D. thesis is to re-draw Nature’s biochemical boundaries by establishing a novel metabolic architecture that hosts reactions involving F. To fulfil this challenge, the soil bacterium Pseudomonas putida represents an ideal biotechnological platform since it has an extremely flexible metabolism that enables adaptation to many different physicochemical conditions and to high concentrations of toxic substances. I will engineer P. putida to provide highly valuable fluorinated building blocks for chemical syntheses from inexpensive resources. Since my projects include extensive genome editing, I also work actively in optimizing and extending the available synthetic biology toolbox for genome manipulation of P. putida.