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Improved production of clavulanic acid by reverse engineering and overexpression of the regulatory genes in an industrial Streptomyces clavuligerus strain

Title
Improved production of clavulanic acid by reverse engineering and overexpression of the regulatory genes in an industrial Streptomyces clavuligerus strain
Authors
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
윤여준
SCOPUS Author ID
윤여준scopus
Issue Date
2019
Journal Title
Journal of Industrial Microbiology and Biotechnology
ISSN
1367-5435JCR Link
Citation
Journal of Industrial Microbiology and Biotechnology vol. 46, no. 8, pp. 1205 - 1215
Keywords
Clavulanic acidMetabolic engineeringReverse engineeringStreptomyces clavuligerus
Publisher
Springer Verlag
Indexed
SCI; SCIE; SCOPUS scopus
Document Type
Article
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. © 2019, Society for Industrial Microbiology and Biotechnology.
DOI
10.1007/s10295-019-02196-0
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자연과학대학 > 화학·나노과학전공 > Journal papers
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