Redesigning thiamin synthesis: Prospects and potential payoffs
Redesigning thiamin synthesis: Prospects and potential payoffs
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DOI：
10.1016/j.plantsci.2018.01.019
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发表时间：
2018-08-01
期刊：
影响因子：
5.2
通讯作者：
Ding, Yousong
中科院分区：
文献类型：
--
作者：
Hanson, Andrew D.;Amthor, Jeffrey S.;Ding, Yousong
硫胺素是植物生长所必需的，但在体内是短暂的，并且产生使硫胺素生物合成成为通过重新设计进行改进的主要目标的组合在能量上非常昂贵。硫胺素由噻唑和嘧啶部分组成。其高生物合成成本源于使用自杀酶THI 4形成噻唑和使用近自杀酶THIC形成嘧啶。这些能量成本降低了生物质产量潜力，并可能因破坏硫胺素的环境压力而加剧，从而增加了必须制造硫胺素的速度。通过重构硫胺素生物合成途径，消除自杀性THI4和THIC反应，可以大幅削减能源成本。为了证实这一设计概念，我们首先记录了THI4和THIC步骤在途径中的能量成本，并解释了如何削减这些成本可以大幅增加作物生物量和谷物产量。然后，我们表明，重构的途径必须产生硫胺素本身，而不是一个剥离下来的类似物，因为硫胺素分子不能被简化而不失去生物活性。最后，我们考虑可能的节能替代品的效率低下的自然THI4和THIC介导的步骤。
Thiamin is essential for plant growth but is short-lived in vivo and energetically very costly to produce a combination that makes thiamin biosynthesis a prime target for improvement by redesign. Thiamin consists of thiazole and pyrimidine moieties. Its high biosynthetic cost stems from use of the suicide enzyme THI4 to form the thiazole and the near-suicide enzyme THIC to form the pyrimidine. These energetic costs lower biomass yield potential and are likely compounded by environmental stresses that destroy thiamin and hence increase the rate at which it must be made. The energy costs could be slashed by refactoring the thiamin biosynthesis pathway to eliminate the suicidal THI4 and THIC reactions. To substantiate this design concept, we first document the energetic costs of the THI4 and THIC steps in the pathway and explain how cutting these costs could substantially increase crop biomass and grain yields. We then show that a refactored pathway must produce thiamin itself rather than a stripped-down analog because the thiamin molecule cannot be simplified without losing biological activity. Lastly, we consider possible energy-efficient alternatives to the inefficient natural THI4- and THIC-mediated steps.