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提高用于平台化学品生产的连续发酵的稳定性。

Enhancing the stability of continuous fermentations for platform chemical production.

作者信息

Outram Victoria, Yiakoumetti Andrew, Green Charlotte, King Rebekah, Ward John M, Conradie Alex

机构信息

Sustainable Process Technologies, Faculty of Engineering, University of Nottingham, University Park, Nottingham NG7 2RD, UK.

Department of Biochemical Engineering, University College London, Bernard Katz Building, Gower Street, London WC1E 6BT, UK.

出版信息

iScience. 2025 Jan 30;28(3):111786. doi: 10.1016/j.isci.2025.111786. eCollection 2025 Mar 21.

Abstract

A significant bottleneck of continuous fermentation is the stability of plasmid-based expression systems. This work tested five plasmid addiction systems based on essential gene complementation in continuous fermentation. The essential genes tested were , , , , and and evaluated under phosphate-limited continuous fermentation at two dilution rates (0.033 h and 0.1 h) and two temperatures (30°C and 37°C). Of these, plasmids stabilized by , , and complementation were segregationally stable under all operating conditions. While a lower dilution rate decreased structural stability, this could be remedied by lowering the temperature. At 0.033 h and 30°C, addiction systems based on , , and complementation conferred segregational stability with no detriment to structural stability, enabling higher yields at lower dilution rates. This work expands the potential of continuous fermentations for bio-based platform chemical production using plasmid addiction systems to ensure plasmid stability.

摘要

连续发酵的一个重大瓶颈是基于质粒的表达系统的稳定性。这项工作在连续发酵中测试了五种基于必需基因互补的质粒成瘾系统。所测试的必需基因有 、 、 、 和 ,并在两种稀释率(0.033 h⁻¹ 和 0.1 h⁻¹)以及两种温度(30°C 和 37°C)下的磷酸盐限制连续发酵条件下进行评估。其中,通过 、 和 互补稳定的质粒在所有操作条件下都是分离稳定的。虽然较低的稀释率会降低结构稳定性,但这可以通过降低温度来补救。在 0.033 h⁻¹ 和 30°C 条件下,基于 、 和 互补的成瘾系统赋予了分离稳定性,且对结构稳定性没有损害,从而能够在较低稀释率下实现更高的产量。这项工作扩展了利用质粒成瘾系统确保质粒稳定性进行基于生物的平台化学品生产的连续发酵的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/151f/11875142/de675c70a238/gr1.jpg

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