(6dr) Engineering Microbial Production Platforms for Efficient Carbon Utilization

Microbial production platforms promise to be a sustainable alternative to today’s petrochemical industry.  By harnessing the breadth and flexibility of cellular metabolism to process available energy sources, ‘living foundries’ can be engineered that convert renewable sugar feedstocks directly into a number of enantiopure commodity and high-value specialty chemicals.  Despite isolated successes, however, these platforms have been unable to scale to meet the gap created by increasing oil prices 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.

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 product classes within E. coli 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 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.

In the future, my research program will focus on the development of next generation microbial platforms with applications in sustainability, health and energy.  My approach is to use the tools of data-driven science to formulate novel hypotheses and elucidate emergent systems-level properties of native systems, and engineer innovative solutions with synthetic biology which exploit robust and versatile features of microorganisms.