Targeting metabolic driving and minimization of by-products synthesis for high-yield production of D-pantothenate in Escherichia coli.

Biotechnol J

Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, P. R. China.

Published: January 2022

Background: d-Pantothenate (DPA) is an important functional chemical that has been widely applied in healthcare, cosmetics, animal food, and feed industries.

Methods And Results: In this study, a high-yield DPA-producing strain was constructed by metabolic engineering strategies with targeting metabolic driving and by-products minimization. The metabolic driving force of push and pull was firstly obtained to improve the production of DPA via enrichment of precursor pool and synthetic pathway, accumulating 4.29 g L DPA in shake flask fermentation. To eliminate the metabolic pressure on DPA production, an amino throttling system was proposed and successfully attenuated the synthesis of four competitive amino acids by a single-step regulation of gdhA. Further minimization of acetate was carried out by pta deletion, and utilization of β-alanine was improved via enhancing its uptake system with producing 5.78 g L DPA. Finally, the engineered strain produced 66.39 g L DPA with β-alanine addition in fermentor under fed-batch fermentation.

Conclusion: This study paved a foundation for the industrial production of DPA.

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Source
http://dx.doi.org/10.1002/biot.202100431DOI Listing

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