1. Improved production of clavulanic acid by reverse engineering and overexpression of the regulatory genes in an industrial Streptomyces clavuligerus strain.
- Author
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Cho, Hang Soo, Jo, Jin Chul, Shin, Chang-Hun, Lee, Namil, Choi, Joon-Sun, Cho, Byung-Kwan, Roe, Jung-Hye, Kim, Chan-Wha, Kwon, Ho Jeong, and Yoon, Yeo Joon
- Subjects
REGULATOR genes ,REVERSE engineering ,CLAVULANIC acid ,STREPTOMYCES ,FRAMESHIFT mutation ,COMPARATIVE genomics ,GENETIC overexpression - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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