Design and analysis of synthetic carbon fixation pathways
Design and analysis of synthetic carbon fixation pathways
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DOI：
10.1073/pnas.0907176107
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发表时间：
2010-05-11
影响因子：
11.1
通讯作者：
Milo, Ron
中科院分区：
文献类型：
--
作者：
Bar-Even, Arren;Noor, Elad;Milo, Ron
固碳是指二氧化碳被结合到有机化合物中的过程。在水、光和养分丰富的现代农业中，碳固定可能成为一个重要的生长限制因素。因此，提高固定率对于实现粮食和能源生产的可持续性至关重要。最近已经尝试提高Rubisco的速率和特异性，Rubisco是在Calvin-Benson循环中操作的羧化酶;然而，他们只取得了有限的成功。自然界采用了几种替代的碳固定途径，这促使我们询问是否可以设计出更有效的新型合成循环。利用自然界中已知的大约5,000种代谢酶的全部库，我们通过计算确定了替代的碳固定途径，这些途径结合了来自各种生物体的联合收割机现有代谢构件。我们比较了自然和合成途径的基础上的物理化学标准，包括动力学，能量学和拓扑结构。我们的研究表明，一些拟议的合成途径可能具有显着的定量优势，其天然对应物，如整体动力学速率。一个这样的循环，预计比卡尔文-本森循环快两到三倍，使用最有效的羧化酶，磷酸烯醇丙酮酸羧化酶，使用自然进化的C4循环的核心。虽然实施这种替代循环带来了与表达水平，活性，稳定性，定位和调控相关的艰巨挑战，但我们相信我们的研究结果表明，在通过代谢工程和合成生物学提高食品和可再生燃料生产的巨大挑战中，探索令人兴奋的途径。
Carbon fixation is the process by which CO2 is incorporated into organic compounds. In modern agriculture in which water, light, and nutrients can be abundant, carbon fixation could become a significant growth-limiting factor. Hence, increasing the fixation rate is of major importance in the road toward sustainability in food and energy production. There have been recent attempts to improve the rate and specificity of Rubisco, the carboxylating enzyme operating in the Calvin-Benson cycle; however, they have achieved only limited success. Nature employs several alternative carbon fixation pathways, which prompted us to ask whether more efficient novel synthetic cycles could be devised. Using the entire repertoire of approximately 5,000 metabolic enzymes known to occur in nature, we computationally identified alternative carbon fixation pathways that combine existing metabolic building blocks from various organisms. We compared the natural and synthetic pathways based on physicochemical criteria that include kinetics, energetics, and topology. Our study suggests that some of the proposed synthetic pathways could have significant quantitative advantages over their natural counterparts, such as the overall kinetic rate. One such cycle, which is predicted to be two to three times faster than the Calvin-Benson cycle, employs the most effective carboxylating enzyme, phosphoenolpyruvate carboxylase, using the core of the naturally evolved C4 cycle. Although implementing such alternative cycles presents daunting challenges related to expression levels, activity, stability, localization, and regulation, we believe our findings suggest exciting avenues of exploration in the grand challenge of enhancing food and renewable fuel production via metabolic engineering and synthetic biology.