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

2 Citations (Scopus)

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

Keywords

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

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

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