School of Chemical, Materials and Biomedical Engineering, College of Engineering, The University of Georgia, Athens, GA, 30602, USA.
BiotecEra Inc., 220 Riverbend Rd., Athens, GA, 30602, USA.
Metab Eng. 2019 Sep;55:191-200. doi: 10.1016/j.ymben.2019.07.011. Epub 2019 Jul 23.
Microbial-based chemical synthesis serves as a promising approach for sustainable production of industrially important products. However, limited production performance caused by metabolic burden or genetic variations poses one of the major challenges in achieving an economically viable biomanufacturing process. To address this issue, one superior strategy is to couple the product synthesis with cellular growth, which renders production obligatory for cell survival. Here we create a pyruvate-driven metabolic scenario in engineered Escherichia coli for growth-coupled bioproduction, with which we demonstrate its application in boosting production of anthranilate and its derivatives. Deletion of a minimal set of endogenous pyruvate-releasing pathways engenders anthranilate synthesis as the salvage route for pyruvate generation to support cell growth, concomitant with simultaneous anthranilate production. Further introduction of native and non-native downstream pathways affords production enhancement of two anthranilate-derived high-value products including L-tryptophan and cis, cis-muconic acid from different carbon sources. The work reported here presents a new growth-coupled strategy with demonstrated feasibility for promoting microbial production.
微生物化学合成是一种很有前途的可持续生产工业重要产品的方法。然而，代谢负担或遗传变异导致的有限生产性能是实现经济可行的生物制造过程的主要挑战之一。为了解决这个问题，一种优越的策略是将产物合成与细胞生长偶联，使产物的合成成为细胞生存所必需的。在这里，我们在工程大肠杆菌中创建了一个丙酮酸驱动的代谢情景，用于生长偶联的生物生产，并用它来展示其在提高邻氨基苯甲酸及其衍生物生产中的应用。删除一组最小的内源性丙酮酸释放途径，使邻氨基苯甲酸合成成为丙酮酸生成的补救途径，以支持细胞生长，同时进行邻氨基苯甲酸的生产。进一步引入天然和非天然的下游途径，从不同的碳源生产两种邻氨基苯甲酸衍生的高价值产品，包括 L-色氨酸和顺式，顺式-粘康酸。这里报道的工作提出了一种新的生长偶联策略，证明了其促进微生物生产的可行性。
