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重塑微生物细胞工厂的碳分解代谢物阻遏。

Rewiring carbon catabolite repression for microbial cell factory.

机构信息

School of Nano-Bioscience and Chemical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 689-798, Korea.

出版信息

BMB Rep. 2012 Feb;45(2):59-70. doi: 10.5483/BMBRep.2012.45.2.59.

DOI:10.5483/BMBRep.2012.45.2.59
PMID:22360882
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.

摘要

碳分解代谢物阻遏(CCR)是大多数微生物中发现的一种关键调控系统,它确保了对节能碳源的优先利用。CCR 有助于微生物在代谢能力和最大糖摄取能力之间取得适当的平衡。它还限制了对首选同源底物的不受调节的利用,使微生物能够在自然环境中生存和占主导地位。另一方面,微生物利用多种比例的碳源(如木质纤维素衍生的糖混合物)生产生物制品的能力存在着顽强的瓶颈。优先糖摄取加上对较少优选糖的转录和/或酶排除,成为提高发酵过程产率和生产力的主要障碍之一。未使用的底物的积累也使用于提取所需产物的下游工艺变得复杂。为了克服这一困难并为特定的代谢工程目标开发定制菌株,定量和系统地了解 CCR 背后的分子相互作用图谱是先决条件。在这里,我们比较地综述了 CCR 电路的普遍和菌株特异性特征,并讨论了最近在开发无 CCR 的合成细胞工厂,特别是用于木质纤维素基生物炼制方面的努力。

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