Understanding and elimination of carbon catabolite repression in Escherichia coli

Abstract

Microorganisms often encounter a mixture of different carbon sources and therefore have control systems to selectively take up and metabolize those substrates that promise the best success in competition with other species through rapid growth. The aim of this thesis is to understand and eliminate carbon catabolite repression (CCR) in Escherichia coli for efficient utilization of multiple energy and carbon sources simultaneously. We studied a new CCR hierarchy that causes the preferential utilization of sugars (arabinose, galactose, glucose, mannose, and xylose) over a short-chain fatty acid (propionate). Meanwhile, the native promoters of xylose catabolic genes and xylose transporter genes were replaced with synthetic constitutive promoters to construct an E. coli strain capable of co-metabolizing glucose and xylose by eliminating the CCR of xylose metabolism by glucose. We showed that such an approach can provide a potential to eliminate CCR. This knowledge will be valuable to help strain improvement strategies for the simultaneous consumption of sugar mixtures, leading to shorter fermentation time and higher substrate range and productivity.