(4dp) Engineering Microbial Production Platforms for Efficient Carbon Utilization

The diverse chemistries of cellular metabolism make microbial systems an attractive solution to grand challenges in bioenergy, sustainability and human health.  Among these are successes in the production of high-valued bulk and specialty chemicals such as isoprene and artemisinic acid (an antimalarial agent).  The full economic potential of such systems, however, remains unrealized due to challenges inherent in driving carbon flux towards the desired product.  Drawing on tools from synthetic biology, metabolic engineering, systems biology, and next generation sequencing and synthesis, my research has focused on the development of molecular strategies to increase the viability of these processes, and the elucidation of cellular responses to such intervention.  My overall goal is to elucidate fundamental cellular strategies for the design of efficient metabolic pathways in next generation microbial production platforms which exploit robust and versatile features of microorganisms.

Here, I present my work towards the engineering of more efficient bacterial and eukaryotic systems.  In my doctoral research (with Kristala Prather, Chemical Engineering, MIT), I developed transcriptional and post-transcriptional tools that dynamically divert carbon from central metabolism into a pathway of interest in E. coli.  These tools pave the way for the development of new classes of metabolic pathways and compounds and allow for the optimization of existing pathways by reducing carbon waste.  As a postdoc (with Michelle O’Malley, Chemical Engineering, UCSB), I am studying the effects of compartmentalized expression of metabolic pathways on productivity.  This approach has tremendous potential to both locally concentrate metabolites and enzymes leading to greater productivity, and limit carbon loss to metabolic side reactions localized elsewhere.  While these examples pursue more efficient carbon utilization, there still remains the challenge of sustainable, cost-effective feedstocks for these processes.  Towards that end, I am also analyzing next generation sequencing data to identify novel biomass-degrading enzymes from anaerobic gut fungi and to elucidate their hydrolytic strategies against diverse lignocellulosic substrates.  Such research strives to secure sustainable feedstocks for biotechnology and presents a unique opportunity to examine novel design strategies in a non-model organism.