CAREER: Unraveling the impact of decoupling the carbon metabolism of microbial cell factories on bioproduction

Arizona State University, Scottsdale AZ

Investigators

Abstract

The need for cells to grow and thrive often limits the yield and rate of synthesis of a desired product. The cell balances the flows of energy and material, usually carbon, between these two activities. This limitation arises because cells tend to use a single carbon and energy source at a time. Modifying metabolism to utilize two sources at the same time could alleviate the limitation. Directing each source solely to either growth or product formation could abolish the current limitations. Applying computational approaches will facilitate achievement of these modifications. Designing a flexible biorefinery utilizing renewable feedstocks other than carbon dioxide and sugars is the goal. The project will also provide opportunities for undergraduate students, including students from two tribal schools, Navajo Technical University and Tohono O'odham Community College. The idea that decoupling carbon metabolism into compartments, wherein carbon flux through each compartment has its origin from a different carbon substrate, will lead to increased product titer, rate, and yield is the central hypothesis underlying this project. A metabolism decoupling toolbox based on genome scale modeling will be developed to aid in the identification of compartments within metabolic networks. The above hypothesis will be explored for two scenarios. In one case, two carbon substrates will be converted into two products in a single cell of the cyanobacterium Synechococcus sp. PCC 11901. The other case will use Corynebacterium glutamicum to valorize lignin while maintaining itself by metabolizing glucose. In addition, 13C-pathway analysis will be used to explore the metabolism of the engineered strains and to further understand the carbon contribution of the two carbon substrates towards bioproduction. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.