Enhancement of Clavulanic Acid by Replicative and Integrative Expressionof ccaR and cas2 in Streptomyces clavuligerus NRRL3585

• Published in: Journal of microbiology and biotechnology pp. 1538 - 1545
• Main Authors: HUNG, TRINH VIET, SAILESH MALLA, BYOUNG CHUL PARK, 류광경, HEI CHAN LEE, 송재경
• Format: Journal Article
• Language: Korean
• Published: 한국미생물·생명공학회 01.09.2007
• Subjects: 생물학
• ISSN: 1017-7825

Clavulanic acid (CA) is an inhibitor of β-lactamasethat is produced from Streptomyces clavuligerus NRL3585treatments. In order to increase the production of CA, thereplicative and integrative expresions of ccaR (encoding fora specific regulator of the CA biosynthetic operon) and cas2(encoding for the rate-limiting enzyme in the CA biosyntheticpathway) were applied. Six recombinant plasmids were designedfor this study. The pIBRHL1, pIBRHL3, and pIBRHL13 wereconstructed for overexpression, whereas pNQ3, pNQ2, andpNQ1 were constructed for chromosomal integration withccaR, cas2, and caR-cas2, respectively. All of these plasmidswere transformed into S. clavuligerus NRRL3585. CA productionin transformants resulted in a significantly enhanced amountgreater than that of the wild type, a 2.25-fold increase withpIBRHL1, a 9.28-fold increase with pNQ3, a 5.06-foldincrease with pIBRHL3, a 2.93-fold increase with pNQ2integration, a 5.79-fold increase with pIBRHL13, and a 23.8-fold increase with pNQ1. The integrative pNQ1 strain hasbeen successfully applied to enhance production. KCI Citation Count: 1