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

Hang Soo Cho, Jin Chul Jo, Chang Hun Shin, Namil Lee, Joon Sun Choi, Byung Kwan Cho, Jung Hye Roe, Chan Wha Kim, Ho Jeong Kwon, Yeo Joon Yoon

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalJournal of Industrial Microbiology and Biotechnology
DOIs
Publication statusPublished - 2019 Jan 1

Fingerprint

Clavulanic Acid
Reverse engineering
Streptomyces
Regulator Genes
Genes
Acids
Metabolic engineering
Fermenters
Metabolic Engineering
Mutagenesis
Frameshift Mutation
Gene encoding

Keywords

  • Clavulanic acid
  • Metabolic engineering
  • Reverse engineering
  • Streptomyces clavuligerus

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

Cite this

Improved production of clavulanic acid by reverse engineering and overexpression of the regulatory genes in an industrial Streptomyces clavuligerus strain. / 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; Yoon, Yeo Joon.

In: Journal of Industrial Microbiology and Biotechnology, 01.01.2019.

Research output: Contribution to journalArticle

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 ; Yoon, Yeo Joon. / Improved production of clavulanic acid by reverse engineering and overexpression of the regulatory genes in an industrial Streptomyces clavuligerus strain. In: Journal of Industrial Microbiology and Biotechnology. 2019.
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AU - Choi, Joon Sun

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