Pablo I. Nikel

I received my PhD degree in Molecular Biology & Biotechnology from the University of San Martín (Buenos Aires, Argentina) in 2009. After receiving training in quantitative physiology techniques in USA, I wanted to further develop my skills in a laboratory interested in Systems Biology approaches of industrially-relevant microorganisms. Over the last few years, I have been carrying post-doctoral research in Prof. de Lorenzo’s Laboratory with financial support from the European Molecular Biology Organization (EMBO) and the Marie Skłodowska-Curie Actions Program from the EC.

My general scientific interests revolve around how bacteria adapt their central metabolic pathways in response to environmental cues. The focus of my projects is not only on the curiosity-driven exploration of the metabolic lifestyle of environmental bacteria, but also the rational application of this information in metabolic engineering strategies. In this sense, Pseudomonas putida is often considered a treasure trove of metabolic and degradation activities that can be harnessed for different purposes – but how did this bug gear its central metabolism to cope with the challenges of the highly polluted sites it usually thrives in? The general objective of my research project is therefore to increase the current understanding of the regulation of metabolic pathways in P. putida by applying systems and synthetic biology methods to assist in elucidating and quantifying metabolic properties of the cells.

With a focus on diversity rather than efficiency, the central metabolism of this bacterium is geared for the catabolism of a large variety of substrates, especially organic acids. From an industrial point of view, it would be rather useful to have P. putida strains that efficiently use readily available carbon substrates (inter alia, glucose), and also able to grow under different conditions of oxygen availability. In order to re-design and engineer these relevant properties, the very central metabolic core of P. putida has to be streamlined for these purposes. We have explored the operation of the central carbon metabolism of P. putida by employing a multi-omic approach (i.e., transcriptomic, metabolomic, and fluxomic). Interestingly, we observed that part of the trioses generated during glucose catabolism are recycled back into hexoses phosphate (see accompanying figure), in a way that suggests that extra redox currency (in the form of NADPH) can be generated by a cyclic operation of components from the Entner-Doudoroff pathway, the (incomplete) Embden-Meyerhof-Parnas pathway, and the pentose phosphate pathway. We are currently investigating the reasons of such conspicuous metabolic architecture and the potential consequences it may have both from an environmental and an applied point of view. In a parallel project, closely connected with the metabolic features of P. putida described above, we will attempt to detach both small and large metabolic modules from the rest of the metabolic network (i.e., metabolic orthogonalization) in order to re-direct key metabolic intermediates into alternative native and heterologous pathways. Finally, I am also interested in the development of Synthetic Biology tools that can be used for the generation of efficient microbial cell factories.

Fig_Pag_web_Pablo

Central carbon metabolism in Pseudomonas putida. The architecture of central carbon metabolism is shown along the key elements belonging to the Entner-Doudoroff pathway (in green), the (incomplete) Embden-Meyerhof-Parnas pathway (in purple), and the pentose phosphate pathway (in red). Key metabolites are highlighted in blue along with the enzymes involved in their biochemical transformations. Reactions downwards pyruvate are collectively indicated with a wide shaded arrow.