Du Wei, Jongbloets Joeri A, Guillaume Max, van de Putte Bram, Battaglino Beatrice, Hellingwerf Klaas J, Branco Dos Santos Filipe
Molecular Microbial Physiology Group, Faculty of Life Sciences, Swammerdam Institute of Life Sciences , University of Amsterdam , Science Park 904 , 1098 XH Amsterdam , The Netherlands.
Applied Science and Technology Department , Politecnico di Torino , Corso Duca degli Abruzzi 24 , 10129 Torino , Italy.
ACS Synth Biol. 2019 Oct 18;8(10):2263-2269. doi: 10.1021/acssynbio.9b00289. Epub 2019 Oct 1.
Cyanobacterial cell factories are widely researched for the sustainable production of compounds directly from CO. Their application, however, has been limited for two reasons. First, traditional approaches have been shown to lead to unstable cell factories that lose their production capability when scaled to industrial levels. Second, the alternative approaches developed so far are mostly limited to growing conditions, which are not always the case in industry, where nongrowth periods tend to occur (e.g., darkness). We tackled both by generalizing the concept of growth-coupled production to fitness coupling. The feasibility of this new approach is demonstrated for the production of fumarate by constructing the first stable dual-strategy cell factory. We exploited circadian metabolism using both systems and synthetic biology tools, resulting in the obligatorily coupling of fumarate to either biomass or energy production. Resorting to laboratory evolution experiments, we show that this engineering approach is more stable than conventional methods.
蓝藻细胞工厂因其能够直接从二氧化碳可持续生产化合物而受到广泛研究。然而，其应用受到限制，原因有两个。首先，传统方法已被证明会导致细胞工厂不稳定，在扩大到工业规模时会失去生产能力。其次，迄今为止开发的替代方法大多局限于生长条件，而在工业中情况并非总是如此，工业中往往会出现非生长时期（例如黑暗）。我们通过将生长偶联生产的概念推广到适应性偶联来解决这两个问题。通过构建第一个稳定的双策略细胞工厂，证明了这种新方法用于生产富马酸盐的可行性。我们利用系统和合成生物学工具开发昼夜节律代谢，从而使富马酸盐与生物量或能量生产必然偶联。通过实验室进化实验，我们表明这种工程方法比传统方法更稳定。
