Improved production of clavulanic acid by reverse engineering and overexpression of the regulatory genes in an industrial Streptomyces clavuligerus strain.
J Ind Microbiol Biotechnol
; 46(8): 1205-1215, 2019 Aug.
Article
in En
| MEDLINE
| ID: mdl-31165280
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Streptomyces
/
Gene Expression Regulation, Bacterial
/
Clavulanic Acid
/
Mixed Function Oxygenases
Language:
En
Journal:
J Ind Microbiol Biotechnol
Journal subject:
BIOTECNOLOGIA
/
MICROBIOLOGIA
Year:
2019
Document type:
Article