Past Event: Oden Institute Seminar

Using computations to model and reshape metabolism

Costas D. Maranas, Professor, Department of Chemical Engineering, Penn State University, University Park, PATBA

Abstract

Metabolism is defined as the full complement of chemical transformations in living systems. In many biotechnological applications an organism must be endowed with additional metabolic capabilities. To support this goal, we introduced computational tools for constructing thermodynamically feasible, carbon and energy efficient, overall conversion stoichiometries by globally assessing all possible co-reactant/products combinations. Protein engineering, either de novo or through directed evolution, can expand upon the parts-list available for constructing pathways by re-purposing existing enzymes for novel conversions. However, minimizing the use of novel steps and combining them with existing reactions has remained so far elusive. In response to this unmet need, we developed novoStoic, which allows for seamlessly blending known reactions with de novo steps to construct atom and energy balanced pathways using reaction atom mapping information. Atom tracking through reactions also enables metabolic flux elucidation at a genome-scale revealing how the assumptions implied by core metabolic models may propagate in the inference of internal metabolic fluxes. Finally, we will highlight ongoing efforts that make use of multiple flux datasets of deletion mutants to robustly parameterize kinetic models that approach genome-scale for E. coli and other microbes. We will conclude by offering insight and lessons gained from the application of these tools on a variety of bioproduction challenges. Bio Costas D. Maranas is the Donald B. Broughton Professor in the Department of Chemical Engineering at The Pennsylvania State University. He received a Diploma in Chemical Engineering at the Aristotle University, Greece in 1990 and a Ph.D. in Chemical Engineering from Princeton University in 1995. He has been in the faculty of the department of Chemical Engineering at Penn State since 1995. He is the recipient of the Allan P. Colburn Award for Excellence in Publications by a Young Member of AIChE (2002), the Outstanding Young Investigator Award of the Computing and Systems Technology AIChE Division (2006), the S.V. Sotirchos Lectureship at 6th Panhellenic Chemical Engineering Conference (2007), the Penn State Engineering Alumni Society (PSEAS) Premier Research Award (2016) and Outstanding Research Award in (2012). He is a member of a number of journal Editorial Boards including PLOS Computational Biology, BMC Systems Biology, Biotechnology Journal and Metabolic Engineering. He is a Fellow of the American Institute of Medical and Biological Engineering (AIMBE). He is a member of advisory/steering committees for PNNL/EMSL and EcoCyc and the “Use Inspired Research” Lead in the Center for Bioenergy Innovation (CBI) DOE center. The C. Maranas group develops and deploys computational framework informed by systems engineering and mathematical optimization to understand, analyze and redesign metabolism and proteins. Research interests include: Computational protein design; enzyme and antibody engineering; design of protein pores for bioseparations; reconstruction, curation and analysis of metabolic networks; computational strain design and synthetic biology; metabolism of photosynthetic organisms; metabolism of obligatory anaerobes; modeling of microbial communities; optimization theory and algorithms. He has co-authored over 180 refereed journal publications including a textbook on “Optimization Methods in Metabolic Networks” (2016). He has supervised 32 PhD theses with many group alumni occupying leading positions in industry and academia. http://maranasgroup.com