Guillaume Maxwell Calvin, Branco Dos Santos Filipe
Molecular Microbial Physiology Group, Swammerdam Institute for Life Sciences, Faculty of Science, University of Amsterdam, Science Park 904, Amsterdam 1098 XH, the Netherlands.
Molecular Microbial Physiology Group, Swammerdam Institute for Life Sciences, Faculty of Science, University of Amsterdam, Science Park 904, Amsterdam 1098 XH, the Netherlands.
Curr Opin Biotechnol. 2023 Apr;80:102899. doi: 10.1016/j.copbio.2023.102899. Epub 2023 Jan 30.
Cyanobacteria have promising potential as sustainable cell factories. However, one challenge that is still largely unreported in scaling-up cyanobacteria bioproduction is phenotypic instability, where the emergence and selection of nonproducing cells leading to loss in production has longer evolutionary timescales to take place in industrial-scale bioreactors. Quantifying phenotypic instability early on in strain development allows researchers to make informed decisions on whether to proceed with scalable designs, or if present, devise countermeasures to reduce instability. One particularly effective strategy to mitigate instability is the use of genome-scale metabolic models to design growth-coupled production strains. In silico studies have predicted that creating certain cofactor imbalances or removing recycling reactions in cyanobacteria can be exploited to stably produce a wide variety of metabolites.
蓝细菌作为可持续的细胞工厂具有广阔的潜力。然而，在扩大蓝细菌生物生产规模方面，一个仍未得到充分报道的挑战是表型不稳定性，即在工业规模的生物反应器中，非生产性细胞的出现和选择导致产量损失，这需要更长的进化时间尺度。在菌株开发的早期阶段对表型不稳定性进行量化，有助于研究人员就是否采用可扩展设计做出明智的决策，或者如果存在表型不稳定性，制定对策以降低不稳定性。减轻不稳定性的一种特别有效的策略是使用基因组规模的代谢模型来设计生长偶联型生产菌株。计算机模拟研究预测，在蓝细菌中制造某些辅因子失衡或去除循环反应，可用于稳定生产多种代谢物。
