Improved production of clavulanic acid by reverse engineering and overexpression of the regulatory genes in an industrial Streptomyces clavuligerus strain
- 주제(키워드) Clavulanic acid , Metabolic engineering , Reverse engineering , Streptomyces clavuligerus
- 등재 SCIE, SCOPUS
- OA유형 Bronze
- 발행기관 Springer Verlag
- 발행년도 2019
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000161344
- 본문언어 영어
- Published As http://dx.doi.org/10.1007/s10295-019-02196-0
- PubMed https://pubmed.ncbi.nlm.nih.gov/31165280
- 저작권 이화여자대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
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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