Jouhten Paula, Huerta-Cepas Jaime, Bork Peer, Patil Kiran Raosaheb
European Molecular Biology Laboratory, Heidelberg, Germany.
European Molecular Biology Laboratory, Heidelberg, Germany; Molecular Medicine Partnership Unit, University of Heidelberg and European Molecular Biology Laboratory, 69117 Heidelberg, Germany; Max Delbrück Centre for Molecular Medicine, 13125 Berlin, Germany; Department of Bioinformatics, Biocenter, University of Würzburg, 97074 Würzburg, Germany.
Metab Eng. 2017 Mar;40:1-4. doi: 10.1016/j.ymben.2017.02.010. Epub 2017 Feb 21.
Microbial cell factories based on renewable carbon sources are fundamental to a sustainable bio-economy. The economic feasibility of producer cells requires robust performance balancing growth and production. However, the inherent competition between these two objectives often leads to instability and reduces productivity. While algorithms exist to design metabolic network reduction strategies for aligning these objectives, the biochemical basis of the growth-product coupling has remained unresolved. Here, we reveal key reactions in the cellular biochemical repertoire as universal anchor reactions for aligning cell growth and production. A necessary condition for a reaction to be an anchor is that it splits a substrate into two or more molecules. By searching the currently known biochemical reaction space, we identify 62 C-C cleaving anchor reactions, such as isocitrate lyase (EC 4.1.3.1) and L-tryptophan indole-lyase (EC 4.1.99.1), which are relevant for biorefining. The here identified anchor reactions mark network nodes for basing growth-coupled metabolic engineering and novel pathway designs.
基于可再生碳源的微生物细胞工厂是可持续生物经济的基础。生产细胞的经济可行性要求在生长和生产之间实现稳健的性能平衡。然而，这两个目标之间固有的竞争往往会导致不稳定性并降低生产力。虽然存在设计代谢网络简化策略以协调这些目标的算法，但生长-生产耦合的生化基础仍未得到解决。在此，我们揭示了细胞生化库中的关键反应，作为协调细胞生长和生产的通用锚定反应。一个反应成为锚定反应的必要条件是它将一种底物分解成两个或更多分子。通过搜索当前已知的生化反应空间，我们鉴定出62种碳-碳裂解锚定反应，如异柠檬酸裂解酶（EC 4.1.3.1）和L-色氨酸吲哚裂解酶（EC 4.1.99.1），它们与生物精炼相关。这里鉴定出的锚定反应为基于生长耦合的代谢工程和新途径设计标记了网络节点。
