High-level and -yield orotic acid production in Escherichia coli through systematic modular engineering and "Chaos to Order Cycles" fermentation.
Bioresour Technol
; : 131345, 2024 Aug 23.
Article
em En
| MEDLINE
| ID: mdl-39182798
ABSTRACT
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 182.5â¯g/L, 0.58â¯g/g, and 3.80â¯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 0.63â¯g/g. This research is a remarkable achievement in orotic acid production by microbial fermentation and has vast potential for industrial applications.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Bioresour Technol
Assunto da revista:
ENGENHARIA BIOMEDICA
Ano de publicação:
2024
Tipo de documento:
Article
País de publicação:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM