Robust Optimization of Metabolic Pathways, a Detailed Step-by-Step

Abstract

Understanding and optimizing the CO2 fixation process would allow human beings to address better current energy and biotechnology issues. My research group and I focused on modeling the C3 photosynthetic Carbon metabolism pathway with the aim of identifying the minimal set of enzymes whose biotechnological alteration could allow a functional re-engineering of the pathway. To achieve this result we merged in a single powerful pipeline Sensitivity Analysis (SA), Single- (SO) and Multi-Objective Optimization (MO) and Robustness Analysis (RA). By using our recently developed multipurpose optimization algorithms we extend our work exploring a large combinatorial solution space and most importantly, here we present an important reduction of the problem search space. From the initial number of 23 enzymes we have identified 11 enzymes whose targeting in the C3 photosynthetic Carbon metabolism would provide about 90% of the overall functional optimization. Both in terms of maximal CO2 Uptake and minimal Nitrogen consumption, these 11 sensitive enzymes are confirmed to play a key role. Finally it will be presented a Robustness Analysis to confirm our findings. On a separate track it will be detailed how Geobacter Sulfurreducens metabolism could be re-engineered, keeping biological constraints which are functional for the bacteria, moving towards functional strains which might be directly useful for biomass employment and electron production.

Bio: Dr. Renato Umeton earned his education at University of Calabria, Italy: both BS and MS in Computer Science, and his PhD in Mathematics and Informatics in 2010 with the thesis "Optimization and Ontology for Computational and Systems Biology". Since year 2008 he shares a research track with Professor Giuseppe Nicosia (U. Catania), Professor Pietro Lio' (U. of Cambridge, UK) and Dr. Giovanni Stracquadanio (Johns Hopkins University), whose aim is the investigation of metabolic pathways and their robust optimization; the Carbon metabolism and the Geobacter Sulfurreducens metabolism are currently studied. Since 2009 he is involved in a Harvard/MIT joint program; at MIT he spent 1.5 years in the laboratory of Professor C. Forbes Dewey. In this context he participates in an on- going research on the development of new computational paradigms for the ontological integration of biochemical information. In early 2011 he got hired as Postdoctoral research associate at Sapienza, University of Rome, at the Medical School, S. Andrea Hospital-site; there, in Professor Marco Salvetti group he studies Multiple Sclerosis, integrating (i) patient-centric bioinformatics information, (ii) ontology-aware evaluation of typical wet-lab experiments and (iii) and single-patient genetic data.