Marschall Lukas, Sagmeister Patrick, Herwig Christoph
Institute of Chemical Engineering, Research Area Biochemical Engineering, Vienna University of Technology, Vienna, Austria.
Exputec GmbH, Vienna, Austria.
Appl Microbiol Biotechnol. 2017 Jan;101(2):501-512. doi: 10.1007/s00253-016-8045-z. Epub 2016 Dec 21.
Tuning of transcription is a promising strategy to overcome challenges associated with a non-suitable expression rate like outgrowth of segregants, inclusion body formation, metabolic burden and inefficient translocation. By adjusting the expression rate-even on line-to purposeful levels higher product titres and more cost-efficient production processes can be achieved by enabling culture long-term stability and constant product quality. Some tunable systems are registered for patents or already commercially available. Within this contribution, we discuss the induction mechanisms of various Escherichia coli inherent promoter systems with respect to their tunability and review studies using these systems for expression tuning. According to the current level of knowledge, some promoter systems were successfully used for expression tuning, and in some cases, analytical evidence on single-cell level is still pending. However, only a few studies using tunable strains apply a suitable process control strategy. So far, expression tuning has only gathered little attention, but we anticipate that expression tuning harbours great potential for enabling and optimizing the production of a broad spectrum of products in E. coli.
转录调控是一种很有前景的策略，可用于克服与不合适的表达速率相关的挑战，如分离菌的生长、包涵体形成、代谢负担和低效转运。通过调整表达速率——即使是在线调整到目标水平，也可以通过实现培养物的长期稳定性和恒定的产品质量来获得更高的产品滴度和更具成本效益的生产过程。一些可调控系统已申请专利或已在商业上可用。在本论文中，我们讨论了各种大肠杆菌固有启动子系统的诱导机制及其可调控性，并综述了使用这些系统进行表达调控的研究。根据目前的知识水平，一些启动子系统已成功用于表达调控，在某些情况下，单细胞水平的分析证据仍有待确定。然而，只有少数使用可调控菌株的研究应用了合适的过程控制策略。到目前为止，表达调控只受到了很少的关注，但我们预计，表达调控在实现和优化大肠杆菌中广泛产品的生产方面具有巨大潜力。
