Enhanced production of clavulanic acid by improving glycerol utilization using reporter-guided mutagenesis of an industrial Streptomyces clavuligerus strain. (25th January 2021)

• Record Type: Journal Article
• Authors: Shin, Chang-Hun; Cho, Hang Su; Won, Hyung-Jin; Kwon, Ho Jeong; Kim, Chan-Wha; Yoon, Yeo Joon
• Is Part Of: Journal of industrial microbiology & biotechnology. Volume 48:Number 3/4(2021)
• Publication Date: 2021-01-25
• Subjects: Clavulanic acid -- Streptomyces clavuligerus -- Glycerol utilization -- Reporter-guided selection; Industrial microbiology -- Periodicals; 660.62
• DOI: 10.1093/jimb/kuab004
• Languages: English
• ISSNs: 1367-5435

Abstract

Abstract: Clavulanic acid (CA) produced by Streptomyces clavuligerus is a clinically important β-lactamase inhibitor. It is known that glycerol utilization can significantly improve cell growth and CA production of S. clavuligerus . We found that the industrial CA-producing S. clavuligerus strain OR generated by random mutagenesis consumes less glycerol than the wild-type strain; we then developed a mutant strain in which the glycerol utilization operon is overexpressed, as compared to the parent OR strain, through iterative random mutagenesis and reporter-guided selection. The CA production of the resulting S. clavuligerus ORUN strain was increased by approximately 31.3% (5.21 ± 0.26 g/l) in a flask culture and 17.4% (6.11 ± 0.36 g/l) in a fermenter culture, as compared to that of the starting OR strain. These results confirmed the important role of glycerol utilization in CA production and demonstrated that reporter-guided mutant selection is an efficient method for further improvement of randomly mutagenized industrial strains.