Application of 8-parallel micro-bioreactor system with non-invasive optical pH and DO biosensor in high-throughput screening of l-lactic acid producing strain

Abstract

Background

Compared with shake flask, bioreactor offers a relatively stable and controllable extracellular environment for cell growth and metabolism. Meanwhile, parallel micro-bioreactor system could well meet the screening flux requirement in the process of high-throughput strain screening. In this study, a self-developed 8-parallel micro-bioreactor system with non-invasive optical biosensors was introduced to substitute the traditional shake flask.

Results

Optical pH and DO biosensors could be well applied for the process monitoring and controlling in the cultures of commonly used microorganisms through maintaining constant temperature and bioreactor shading treatment. Subsequently, 8-parallel micro-bioreactor system was adopted in the rescreening procedure of high-throughput screening process, and it significantly increased the feasibility of scaling up a cultivating system without any sacrifice on the screening flux. As a result, a designated mutant strain Lactobacillus paracasei S4 was obtained, which presented an improvement of 18.9% on titer value of l-lactic acid. Moreover, the yield also increased from 0.903 ± 0.005 to 0.932 ± 0.013 g/g.

Conclusion

In this study, the micro-bioreactor system proved to be applicable and effective in the rescreening procedure of high-throughput screening process. The adopted approach provided a robust tool for screening the strain with high l-lactic acid producing performance.

Keywords

High-throughput screening / Lactic acid / Lactobacillus paracasei / Micro-bioreactor / Optical biosensor

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Funding

National Science Foundation for Young Scientists of China(31700038)

National Key Research and Development Program(2017YFB0309302)

the National Major Scientific Technological Special Project(2012YQ15008706)