Fluorine is a key element for the synthesis of molecules broadly used in medicine, agriculture, and materials. Adding fluorine atoms onto organic structures is a unique strategy for tuning molecular properties—yet organofluorines are rarely found in Nature, and approaches to integrate fluorometabolites into the chemistry of living cells are scarce. In this seminar, I will also discuss how synthetic metabolism can be implemented to expand the chemical landscape of bacteria, thus providing alternative biosynthetic strategies for fluorinated building-blocks. This general approach will be illustrated by showing how synthetic gene circuits can be engineered in the platform bacterium Pseudomonas putida for organofluorine biosynthesis. To this end, fluoride-responsive riboswitches, orthogonal RNA polymerases, and novel fluorinating enzymes mined from extreme environments were combined to drive in vivo biofluorination. Biosynthesis of fluoronucleotides and fluorosugars in engineered P. putida is demonstrated with mineral fluoride both as the only fluorine source (i.e., as a substrate of the pathway) and as an inducer of the synthetic circuit. Building on these results, prospects for bioproduction of fluorinated building blocks and materials will be likewise discussed.
About the Speaker:
Pablo I. Nikel earned a Ph.D. in Biotechnology and Molecular Biology (2009) in Buenos Aires, Argentina. During graduate school, his research focused on repurposing two-component signal transduction systems in Escherichia coli to produce biopolymers and biofuels. After receiving training in 13C-based quantitative physiology technologies in the USA (Rice University, supported by the ASM), Pablo moved to Europe in 2011 as a post-doctoral fellow in Prof. de Lorenzo’s laboratory in Madrid, funded by the European Molecular Biology Organization (EMBO) and the Marie Skłodowska-Curie Actions (MSCA) of the European Commission. During his post-doctoral training, he came across the world of environmental bacteria—particularly Pseudomonas putida. Inspired by this bacterium's unique possibilities for bioengineering, he is now leading the Systems Environmental Microbiology Group at DTU Biosustain. Pablo’s team aims to rewrite P. putida’s core biochemistry through synthetic metabolism for the biosynthesis of novel compounds, focusing on new-to-nature fine chemicals (www.sem-cfb.com). The ultimate ambition of this research program is to expand the limits of microbial biochemistry—granting access to compounds exclusively produced via traditional chemistry nowadays. Pablo also coordinates the H2020 project SinFonia (www.sinfoniabiotec.eu) and full Professor at the Technical University of Denmark (2023).