Organization of Advanced Science and Technology, Kobe University, Rokkodaicho, Nada-ku, Kobe, Hyogo, Japan.
Microb Cell Fact. 2011 Sep 8;10:70. doi: 10.1186/1475-2859-10-70.
While Saccharomyces cerevisiae is a promising host for cost-effective biorefinary processes due to its tolerance to various stresses during fermentation, the metabolically engineered S. cerevisiae strains exhibited rather limited production of higher alcohols than that of Escherichia coli. Since the structure of the central metabolism of S. cerevisiae is distinct from that of E. coli, there might be a problem in the structure of the central metabolism of S. cerevisiae. In this study, the potential production of higher alcohols by S. cerevisiae is compared to that of E. coli by employing metabolic simulation techniques. Based on the simulation results, novel metabolic engineering strategies for improving higher alcohol production by S. cerevisiae were investigated by in silico modifications of the metabolic models of S. cerevisiae.
The metabolic simulations confirmed that the high production of butanols and propanols by the metabolically engineered E. coli strains is derived from the flexible behavior of their central metabolism. Reducing this flexibility by gene deletion is an effective strategy to restrict the metabolic states for producing target alcohols. In contrast, the lower yield using S. cerevisiae originates from the structurally limited flexibility of its central metabolism in which gene deletions severely reduced cell growth.
The metabolic simulation demonstrated that the poor productivity of S. cerevisiae was improved by the introduction of E. coli genes to compensate the structural difference. This suggested that gene supplementation is a promising strategy for the metabolic engineering of S. cerevisiae to produce higher alcohols which should be the next challenge for the synthetic bioengineering of S. cerevisiae for the efficient production of higher alcohols.
由于酿酒酵母在发酵过程中能耐受各种压力，因此是一种很有前途的低成本生物炼制工艺宿主，但与大肠杆菌相比，经代谢工程改造的酿酒酵母菌株的高级醇产量相当有限。由于酿酒酵母的中心代谢结构与大肠杆菌不同，因此可能存在酿酒酵母中心代谢结构的问题。在这项研究中，通过代谢模拟技术，比较了酿酒酵母和大肠杆菌的高级醇潜在产量。基于模拟结果，通过对酿酒酵母代谢模型进行计算机模拟修改，研究了提高酿酒酵母高级醇产量的新型代谢工程策略。
代谢模拟证实，经过代谢工程改造的大肠杆菌菌株之所以能够大量生产丁醇和丙醇，是因为其中心代谢具有灵活的行为。通过基因缺失来降低这种灵活性是限制产生目标醇类的代谢状态的有效策略。相比之下，酿酒酵母的产量较低是由于其中心代谢的结构限制了其灵活性，基因缺失严重降低了细胞生长。
代谢模拟表明，通过引入大肠杆菌基因来补偿结构差异，可以提高酿酒酵母的低生产力。这表明基因补充是酿酒酵母代谢工程的一种很有前途的策略，这应该是酿酒酵母的合成生物工程高效生产高级醇的下一个挑战。
