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.
journal_name
J Ind Microbiol Biotechnoljournal_title
Journal of industrial microbiology & biotechnologyauthors
Cho HS,Jo JC,Shin CH,Lee N,Choi JS,Cho BK,Roe JH,Kim CW,Kwon HJ,Yoon YJdoi
10.1007/s10295-019-02196-0subject
Has Abstractpub_date
2019-08-01 00:00:00pages
1205-1215issue
8eissn
1367-5435issn
1476-5535pii
10.1007/s10295-019-02196-0journal_volume
46pub_type
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