Engineering central metabolism – a grand challenge for plant biologists
Engineering central metabolism – a grand challenge for plant biologists
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DOI：
10.1111/tpj.13464
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发表时间：
2017-05
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影响因子：
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通讯作者：
L. Sweetlove;J. Nielsen;A. Fernie
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作者：
L. Sweetlove;J. Nielsen;A. Fernie
许多雄心勃勃的研究项目正在寻求重新设计光合作用生物化学，以实现提高作物生产力和养分利用效率的目标。这些项目中的许多将需要对中枢新陈代谢的通量进行实质性改变。然而，正如在微生物等更简单的系统中已经充分证明的那样，中枢新陈代谢极难理性地设计。这是因为维持代谢稳定状态的多层调控，以及中枢代谢高度相关的本质。在这篇综述中，我们讨论了代谢工程的新方法，这些方法具有解决这些问题的潜力，并极大地提高了我们可以合理地设计植物中央代谢的成功。特别是，我们主张采用迭代的‘设计-建造-测试-学习’循环，使用快速改造的模型工厂作为试验台。这种方法可以通过将新的分子工具与计算机建模相结合来实现，这些工具将核和叶绿体基因组中的多个转基因与设计工程策略和了解工程有机体的代谢表型相结合。我们还设想，突变可以用来微调内源代谢网络和引入的酶之间的平衡。最后，我们强调将植物作为一个完整的系统而不是孤立的器官来考虑的重要性：如果同时设计源代谢和库代谢，将实现作物生产力的最大提高。
The goal of increasing crop productivity and nutrient-use efficiency is being addressed by a number of ambitious research projects seeking to re-engineer photosynthetic biochemistry. Many of these projects will require the engineering of substantial changes in fluxes of central metabolism. However, as has been amply demonstrated in simpler systems such as microbes, central metabolism is extremely difficult to rationally engineer. This is because of multiple layers of regulation that operate to maintain metabolic steady state and because of the highly connected nature of central metabolism. In this review we discuss new approaches for metabolic engineering that have the potential to address these problems and dramatically improve the success with which we can rationally engineer central metabolism in plants. In particular, we advocate the adoption of an iterative 'design-build-test-learn' cycle using fast-to-transform model plants as test beds. This approach can be realised by coupling new molecular tools to incorporate multiple transgenes in nuclear and plastid genomes with computational modelling to design the engineering strategy and to understand the metabolic phenotype of the engineered organism. We also envisage that mutagenesis could be used to fine-tune the balance between the endogenous metabolic network and the introduced enzymes. Finally, we emphasise the importance of considering the plant as a whole system and not isolated organs: the greatest increase in crop productivity will be achieved if both source and sink metabolism are engineered.