Enhanced production of clavulanic acid by improving glycerol utilization using reporter-guided mutagenesis of an industrial Streptomyces clavuligerus strain.
- Resource Type
- Article
- Authors
- Chang-Hun Shin; Hang Su Cho; Hyung-Jin Won; Ho Jeong Kwon; Chan-Wha Kim; Yeo Joon Yoon
- Source
- Journal of Industrial Microbiology & Biotechnology. Apr2021, Vol. 48 Issue 3/4, p1-8. 8p.
- Subject
- *CLAVULANIC acid
*STREPTOMYCES
*MUTAGENESIS
*GLYCERIN
*OPERONS
*CELL growth
- Language
- ISSN
- 1367-5435
Clavulanic acid (CA) produced by Streptomyces clavuligerus is a clinically important ß-lactamase inhibitor. It is known that glycerol utilization can significantly improve cell growth and CA production of S. clavuligerus. We found that the industrial CAproducing 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. [ABSTRACT FROM AUTHOR]