Rewiring carbon catabolite repression for microbial cell factory

Abstract

Carbon catabolite repression (CCR) is a key regulatory system found in most microorganisms that ensures preferential utilization of energy-efficient carbon sources. CCR helps microorganisms obtain a proper balance between their metabolic capacity and the maximum sugar uptake capability. It also constrains the deregulated utilization of a preferred cognate substrate, enabling microorganisms to survive and dominate in natural environments. On the other side of the same coin lies the tenacious bottleneck in microbial production of bioproducts that employs a combination of carbon sources in varied proportion, such as lignocellulose-derived sugar mixtures. Preferential sugar uptake combined with the transcriptional and/or enzymatic exclusion of less preferred sugars turns out one of the major barriers in increasing the yield and productivity of fermentation process. Accumulation of the unused substrate also complicates the downstream processes used to extract the desired product. To overcome this difficulty and to develop tailor-made strains for specific metabolic engineering goals, quantitative and systemic understanding of the molecular interaction map behind CCR is a prerequisite. Here we comparatively review the universal and strain-specific features of CCR circuitry and discuss the recent efforts in developing synthetic cell factories devoid of CCR particularly for lignocellulose-based biorefinery. [BMB reports 2012; 45(2): 59-70]

Reciprocal Regulation ofl-Arabinose andd-Xylose Metabolism in Escherichia coli

“…Not surprisingly, numerous design strategies have been proposed to enable simultaneous sugar utilization in E. coli as well as other bacteria and yeast. Most of these efforts have focused on the coutilization of glucose and another sugar (36). Less effort has been directed toward the coutilization of nonglucose sugar (7,(37)(38)(39).…”

Simultaneous Fermentation of Glucose and Xylose to Butanol by Clostridium sp. Strain BOH3

“…Gu et al have shown that C. acetobutylicum ATCC 824 utilized 86% of glucose within 40 h, whereas only 6% of xylose was consumed even after an elongated incubation time (14). This sequential utilization extends fermentation time and results in incomplete substrate consumption (21,33). The phenomenon of preferring glucose over xylose is referred to as carbon catabolite repression, in which microorganisms preferentially utilize a rapidly metabolizable carbon source and inhibit the expression of some genes and enzyme activities related to the catabolism of nonpreferred carbon resources (21,33).…”

“…This sequential utilization extends fermentation time and results in incomplete substrate consumption (21,33). The phenomenon of preferring glucose over xylose is referred to as carbon catabolite repression, in which microorganisms preferentially utilize a rapidly metabolizable carbon source and inhibit the expression of some genes and enzyme activities related to the catabolism of nonpreferred carbon resources (21,33). Unless glucose and xylose are both utilized efficiently, converting lignocellulosic biomass into biologically based products is unfavorable from an economic viewpoint (19,20,22), as yields would be limited.…”

Soluble Carbohydrates Repress the Cellulolytic Activity of Clostridium cellulovorans and Eubacterium cellulosolvens

“…Originally known as the "glucose effect" [1], this mechanism enables some bacteria to preferentially catabolize certain energy substrates, e.g., Escherichia coli has preference for glucose even when lactose is readily available [2,3]. This "glucose effect" is often referred to as carbon catabolite repression (CCR) [4,5]. Depending upon the bacterial species, CCR involves one or a combination of mechanisms in gram-positive bacteria [2][3][4][5][6][7][8].…”

“…This "glucose effect" is often referred to as carbon catabolite repression (CCR) [4,5]. Depending upon the bacterial species, CCR involves one or a combination of mechanisms in gram-positive bacteria [2][3][4][5][6][7][8]. The repression can also be activated by catabolites other than glucose [2,8,9].…”