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Improved production of clavulanic acid by reverse engineering and overexpression of the regulatory genes in an industrial Streptomyces clavuligerus strain
- Improved production of clavulanic acid by reverse engineering and overexpression of the regulatory genes in an industrial Streptomyces clavuligerus strain
- Cho H.S.; Jo J.C.; Shin C.-H.; Lee N.; Choi J.-S.; Cho B.-K.; Roe J.-H.; Kim C.-W.; Kwon H.J.; Yoon Y.J.
- Ewha Authors
- SCOPUS Author ID
- Issue Date
- Journal Title
- Journal of Industrial Microbiology and Biotechnology
- Journal of Industrial Microbiology and Biotechnology vol. 46, no. 8, pp. 1205 - 1215
- Clavulanic acid; Metabolic engineering; Reverse engineering; Streptomyces clavuligerus
- Springer Verlag
- SCI; SCIE; SCOPUS
- Document Type
- Genomic analysis of the clavulanic acid (CA)-high-producing Streptomyces clavuligerus strains, OL13 and OR, developed through random mutagenesis revealed a frameshift mutation in the cas1 gene-encoding clavaminate synthase 1. Overexpression of the intact cas1 in S. clavuligerus OR enhanced the CA titer by approximately 25%, producing ~ 4.95 g/L of CA, over the OR strain in the flask culture. Moreover, overexpression of the pathway-specific positive regulatory genes, ccaR and claR, in the OR strain improved CA yield by approximately 43% (~ 5.66 g/L) in the flask. However, co-expression of the intact cas1 with ccaR-claR did not further improve CA production. In the 7 L fermenter culture, maximum CA production by the OR strain expressing the wild-type cas1 and ccaR-claR reached approximately 5.52 g/L and 6.01 g/L, respectively, demonstrating that reverse engineering or simple rational metabolic engineering is an efficient method for further improvement of industrial strains. © 2019, Society for Industrial Microbiology and Biotechnology.
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