Wright Naia Risager, Rønnest Nanna Petersen, Sonnenschein Nikolaus
Novo Nordisk A/S, Bagsvaerd, Denmark.
Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark.
Front Bioeng Biotechnol. 2020 Dec 18;8:579841. doi: 10.3389/fbioe.2020.579841. eCollection 2020.
There is a growing interest in continuous manufacturing within the bioprocessing community. In this context, the chemostat process is an important unit operation. The current application of chemostat processes in industry is limited although many high yielding processes are reported in literature. In order to reach the full potential of the chemostat in continuous manufacture, the output should be constant. However, adaptation is often observed resulting in changed productivities over time. The observed adaptation can be coupled to the selective pressure of the nutrient-limited environment in the chemostat. We argue that population heterogeneity should be taken into account when studying adaptation in the chemostat. We propose to investigate adaptation at the single-cell level and discuss the potential of different single-cell technologies, which could be used to increase the understanding of the phenomena. Currently, none of the discussed single-cell technologies fulfill all our criteria but in combination they may reveal important information, which can be used to understand and potentially control the adaptation.
生物加工领域对连续制造的兴趣日益浓厚。在此背景下，恒化器工艺是一项重要的单元操作。尽管文献中报道了许多高产工艺，但目前恒化器工艺在工业中的应用仍然有限。为了在连续制造中充分发挥恒化器的潜力，其产量应保持恒定。然而，人们经常观察到适应性变化，导致生产率随时间改变。观察到的适应性变化可能与恒化器中营养物质受限环境的选择压力有关。我们认为，在研究恒化器中的适应性时，应考虑群体异质性。我们建议在单细胞水平上研究适应性，并讨论不同单细胞技术的潜力，这些技术可用于增进对这些现象的理解。目前，所讨论的单细胞技术均未完全满足我们的所有标准，但综合使用它们可能会揭示重要信息，这些信息可用于理解并潜在地控制适应性。
