Rewiring carbon catabolite repression for microbial cell factory

Carbon catabolite repression (CCR) is a key regulatory systemfound in most microorganisms that ensures preferential utilizationof energy-efficient carbon sources. CCR helps microorganismsobtain a proper balance between their metaboliccapacity and the maximum sugar uptake capability. It alsoconstrains the deregulated utilization of a preferred cognatesubstrate, enabling microorganisms to survive and dominate innatural environments. On the other side of the same coin liesthe tenacious bottleneck in microbial production of bioproductsthat employs a combination of carbon sources in variedproportion, such as lignocellulose-derived sugar mixtures.Preferential sugar uptake combined with the transcriptionaland/or enzymatic exclusion of less preferred sugars turns outone of the major barriers in increasing the yield and productivityof fermentation process. Accumulation of the unusedsubstrate also complicates the downstream processes used toextract the desired product. To overcome this difficulty and todevelop tailor-made strains for specific metabolic engineeringgoals, quantitative and systemic understanding of the molecularinteraction map behind CCR is a prerequisite. Here wecomparatively review the universal and strain-specific featuresof CCR circuitry and discuss the recent efforts in developingsynthetic cell factories devoid of CCR particularly for lignocellulose-based biorefinery. [BMB reports 2012; 45(2): 59-70]