近日，荷兰阿姆斯特丹大学Bob van Sluijs团队报道了定时批量输入解锁酶级联的高产量。相关论文于2026年5月6日发表在《自然-化学》杂志上。
无细胞酶促反应网络（ERNs）能够在单一反应器中生产高价值化合物。然而，别构相互作用、产物抑制、反应可逆性以及对共享辅因子的竞争，只有在ERN组装完成后才会显现出来。这些涌现的动态特性形成了限制总产率的动力学障碍。
研究组提出了一种模型指导的最优设计策略，用于生成批式反应的时间依赖性“配方”，其中每个组分可在任意时间以指定量重复添加。将该方法应用于两个ERN：磷酸戊糖途径和一个分支型核苷酸补救合成途径。在磷酸戊糖途径中，优化输入使AMP产量提高了5.7倍，并采用时间依赖性输入将葡萄糖到产物的转化率从对照组的约12%提升至约48%。在补救合成途径中，时间依赖性加药平衡了竞争性分支，使UTP产率相比组分匹配的一次性加药提高了约21倍。定时分批投料为优化复杂反应序列提供了一种通用途径。
附：英文原文
Title: Timed batch inputs unlock substantially higher yields for enzymatic cascades
Author: Jaktait, Migl, Zhou, Tao, Nelissen, Frank H. T., Huck, Wilhelm T. S., van Sluijs, Bob
Issue&Volume: 2026-05-06
Abstract: Cell-free enzymatic reaction networks (ERNs) enable the production of value-added compounds in a single reaction. However, allosteric interactions, product inhibition, reversibility and competition for shared cofactors only become apparent once the ERN is assembled. These emergent dynamics create kinetic barriers that limit the overall yield. Here we introduce a model-guided optimal design strategy to generate time-dependent ‘recipes’ for batch reactions, in which every component can be added repeatedly at specified amounts, at any time. We apply the method to two ERNs: the pentose phosphate pathway and a branched nucleotide salvage pathway. In the pentose phosphate pathway, optimized inputs increased AMP production up to 5.7-fold and raised glucose-to-product conversion from ~12% in the control to ~48% using a time-dependent input. In the salvage pathway, time-dependent dosing balanced competing branches and increased UTP yield ~21-fold relative to composition-matched all-at-once dosing. Timed batch inputs provide a generally applicable route to optimizing a complex reaction sequence.
DOI: 10.1038/s41557-026-02138-1