Clocking out and letting go to unleash green biotech applications in a photosynthetic host

• 成果类型: Article
• 署名作者: Xu, Yao; Jabbur, Maria Luisa; Mori, Tetsuya; Young, Jamey D.; Johnson, Carl Hirschie
• 署名单位: Vanderbilt University; Vanderbilt University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10684
• DOI: 10.1073/pnas.2318690121
• 发表日期: 2024-05-21
• 关键词: circadian gene-expression; transcriptional control; bacterial luciferase; rhythms; cyanobacteria; identification; oscillations; reporter; SYSTEM

摘要

Cyanobacteria are photosynthetic bacteria whose gene expression patterns are globally regulated by their circadian (daily) clocks. Due to their ability to use sunlight as their energy source, they are also attractive hosts for green production of pharmaceuticals, renewable fuels, and chemicals. However, despite the application of traditional genetic tools such as the identification of strong promoters to enhance the expression of heterologous genes, cyanobacteria have lagged behind other microorganisms such as Escherichia coli and yeast as economically efficient cell factories. The previous approaches have ignored large - scale constraints within cyanobacterial metabolic networks on transcription, predominantly the pervasive control of gene expression by the circadian (daily) clock. Here, we show that reprogramming gene expression by releasing circadian repressor elements in the transcriptional regulatory pathways coupled with inactivation of the central oscillating mechanism enables a dramatic enhancement of expression in cyanobacteria of heterologous genes encoding both catalytically active enzymes and polypeptides of biomedical significance.