Intelligent microbial cell factory with genetic pH shooting (GPS) for cell self-responsive base/acid regulation
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Microbial Cell Factories Open Access
RESEARCH
Intelligent microbial cell factory with genetic pH shooting (GPS) for cell self‑responsive base/ acid regulation Chenyi Li1†, Xiaopeng Gao1,2†, Xiao Peng1, Jinlin Li1, Wenxin Bai1, Jiadong Zhong1, Mengchao He2, Ke Xu1,3, Ying Wang1* and Chun Li1,2,3*
Abstract Background: In industrial fermentation, pH fluctuation resulted from microbial metabolism influences the strain performance and the final production. The common way to control pH is adding acid or alkali after probe detection, which is not a fine-tuned method and often leads to increased costs and complex downstream processing. Here, we constructed an intelligent pH-sensing and controlling genetic circuits called “Genetic pH Shooting (GPS)” to realize microbial self-regulation of pH. Results: In order to achieve the self-regulation of pH, GPS circuits consisting of pH-sensing promoters and acid-/ alkali-producing genes were designed and constructed. Designed pH-sensing promoters in the GPS can respond to high or low pHs and generate acidic or alkaline substances, achieving endogenously self-responsive pH adjustments. Base shooting circuit (BSC) and acid shooting circuit (ASC) were constructed and enabled better cell growth under alkaline or acidic conditions, respectively. Furthermore, the genetic circuits including GPS, BSC and ASC were applied to lycopene production with a higher yield without an artificial pH regulation compared with the control under pH values ranging from 5.0 to 9.0. In scale-up fermentations, the lycopene titer in the engineered strain harboring GPS was increased by 137.3% and ammonia usage decreased by 35.6%. Conclusions: The pH self-regulation achieved through the GPS circuits is helpful to construct intelligent microbial cell factories and reduce the production costs, which would be much useful in industrial applications. Keyword: Genetic pH regulation, Base-regulating circuit, Acid-regulating circuit, Microbial cell factory, Escherichia coli Background pH control in the fermentation process is a widespread concern as its fluctuation results in numerous problems. Cell viability and production can be influenced by the surrounding pH. The activities of enzymes will decrease under an improper pH, and eventually, their biosynthetic *Correspondence: [email protected]; [email protected] † Chenyi Li, Xiaopeng Gao Co-first authors 1 Institute of Biochemical Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, People’s Republic of China Full list of author information is available at the end of the article
efficiencies will reduce. Furthermore, an inappropriate pH can change the fermentation profile of microorganisms. For example, Aspergillus Niger can produce citric acid at an acidic pH, but a higher initial pH will lead to the accumulation of oxalic acid [1]. Therefore, a suitable environmental pH is essential for high fermentation productivity, and the optimization of pH in the fermentation process is critical. However, problems conc
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