Cyanobacterial biofuels: new insights and strain design strategies revealed by computational modeling.
Cyanobacterial biofuels: new insights and strain design strategies revealed by computational modeling.
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DOI：
10.1186/s12934-014-0128-x
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发表时间：
2014-09-19
影响因子：
6.4
通讯作者：
Klamt S
中科院分区：
文献类型：
--
作者：
Erdrich P;Knoop H;Steuer R;Klamt S
蓝藻被越来越多地认为是从阳光、二氧化碳和水中生产可再生生物燃料和化学原料的有前途的细胞工厂。然而，这些生物的大多数生物技术应用仍然具有产量低的特点。因此，提高蓝藻的生产性能仍然是关键的一步。在这项工作中，我们使用了聚球藻的化学计量网络模型。PCC 6803与CASOP和最小割集分析相结合，系统地识别和表征适用于生物燃料合成的菌株设计策略，特别是乙醇和异丁醇。作为一个关键的结果，我们在其他工作的基础上，证明了高阶基因敲除策略存在于该模型中，该策略导致光营养条件下生长与高产生物燃料合成的耦合。列举所有潜在的敲除策略(割集)揭示了所识别的品系设计背后的统一原则，即减少由光合作用电子传递链产生的ATP与NADPH的比率。因此，合适的敲除策略试图阻止循环和其他交替的电子流，从而使ATP和NADPH仅通过其ATP/NADPH比低于生物质合成所需的线性电子流来合成。然后，电池将感兴趣的产品用作过量还原当量的汇。重要的是，计算的干预策略不依赖于最优生长的假设，它们确保在没有光的情况下维持新陈代谢仍然可行。我们的分析进一步表明，通过ATP无用循环或其他ATP浪费机制实现适度增加的ATP周转率，是实现提高生物燃料产量的一个有希望的目标。我们的研究揭示了蓝藻生产生物燃料的合理代谢工程策略的关键原则。结果清楚地表明，与异养生物相比，在光合细菌中实现生长和产物合成的强制性耦合需要根本不同的干预策略。本文的在线版本(doi：10.1186/s12934-0140128-x)包含补充材料，授权用户可以使用。
Cyanobacteria are increasingly recognized as promising cell factories for the production of renewable biofuels and chemical feedstocks from sunlight, CO2, and water. However, most biotechnological applications of these organisms are still characterized by low yields. Increasing the production performance of cyanobacteria remains therefore a crucial step. In this work we use a stoichiometric network model of Synechocystis sp. PCC 6803 in combination with CASOP and minimal cut set analysis to systematically identify and characterize suitable strain design strategies for biofuel synthesis, specifically for ethanol and isobutanol. As a key result, improving upon other works, we demonstrate that higher-order knockout strategies exist in the model that lead to coupling of growth with high-yield biofuel synthesis under phototrophic conditions. Enumerating all potential knockout strategies (cut sets) reveals a unifying principle behind the identified strain designs, namely to reduce the ratio of ATP to NADPH produced by the photosynthetic electron transport chain. Accordingly, suitable knockout strategies seek to block cyclic and other alternate electron flows, such that ATP and NADPH are exclusively synthesized via the linear electron flow whose ATP/NADPH ratio is below that required for biomass synthesis. The products of interest are then utilized by the cell as sinks for reduction equivalents in excess. Importantly, the calculated intervention strategies do not rely on the assumption of optimal growth and they ensure that maintenance metabolism in the absence of light remains feasible. Our analyses furthermore suggest that a moderately increased ATP turnover, realized, for example, by ATP futile cycles or other ATP wasting mechanisms, represents a promising target to achieve increased biofuel yields. Our study reveals key principles of rational metabolic engineering strategies in cyanobacteria towards biofuel production. The results clearly show that achieving obligatory coupling of growth and product synthesis in photosynthetic bacteria requires fundamentally different intervention strategies compared to heterotrophic organisms. The online version of this article (doi:10.1186/s12934-014-0128-x) contains supplementary material, which is available to authorized users.
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DOI：
10.1098/rstb.2000.0704
发表时间：
2000-10-29
影响因子：
6.3
作者：
Bader, MR;von Caemmerer, S;Nakano, H
通讯作者：
Nakano, H
影响因子：
4.3
作者：
Knoop H;Gründel M;Zilliges Y;Lehmann R;Hoffmann S;Lockau W;Steuer R
通讯作者：
Steuer R
影响因子：
--
作者：
Kim J;Reed JL
通讯作者：
Reed JL
影响因子：
1.6
作者：
Klamt, S
通讯作者：
Klamt, S
影响因子：
4.1
作者：
Haedicke, Oliver;Klamt, Steffen
通讯作者：
Klamt, Steffen