High-level and -yield orotic acid production in Escherichia coli through systematic modular engineering and "Chaos to Order Cycles" fermentation.

Autor: Li C; College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, PR China; Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education, Tianjin University of Science & Technology, Tianjin 300457, PR China., Shi T; College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, PR China; Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education, Tianjin University of Science & Technology, Tianjin 300457, PR China., Fan W; College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, PR China; Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education, Tianjin University of Science & Technology, Tianjin 300457, PR China., Yuan M; College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, PR China; Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education, Tianjin University of Science & Technology, Tianjin 300457, PR China., Li L; College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, PR China; Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education, Tianjin University of Science & Technology, Tianjin 300457, PR China., Yu Z; College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, PR China; Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education, Tianjin University of Science & Technology, Tianjin 300457, PR China., Chen Z; College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, PR China; Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education, Tianjin University of Science & Technology, Tianjin 300457, PR China., Xu Q; College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, PR China; Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education, Tianjin University of Science & Technology, Tianjin 300457, PR China. Electronic address: xuqingyang@tust.edu.cn.
Jazyk: angličtina
Zdroj: Bioresource technology [Bioresour Technol] 2024 Nov; Vol. 411, pp. 131345. Date of Electronic Publication: 2024 Aug 23.
DOI: 10.1016/j.biortech.2024.131345
Abstrakt: Orotic acid is widely used in healthcare and cosmetic industries. However, orotic acid-producing microorganisms are auxotrophic, which results in inefficient microbial production. Herein, a plasmid-free, uninduced, non-auxotrophic orotic acid hyperproducer was constructed from Escherichia coli W3110. Initially, the orotic acid degradation pathway was blocked and the carbamoyl phosphate supply was enriched. Subsequently, pyr operon from Bacillus subtilis F126 was heterologously expressed and precursors' supply was optimized. Thereafter, pyrE was dynamically regulated to reconstruct the non-auxotrophic pathway. Employing fed-batch cultivation, orotic acid titer, yield, and productivity of strain Ora21 reached 182.5 g/L, 0.58 g/g, and 3.80 g/L/h, respectively, the highest levels reported so far. Finally, a novel "Chaos to Order Cycles (COC)" fermentation was developed, which effectively increased the yield to 0.63 g/g. This research is a remarkable achievement in orotic acid production by microbial fermentation and has vast potential for industrial applications.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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