%0 Journal Article
%T Role of sgcR3 in positive regulation of enediyne antibiotic C-1027 production of Streptomyces globisporus C-1027
%A Lifei Wang
%A Yunfeng Hu
%A Yanjuan Zhang
%A Songmei Wang
%A Zhihui Cui
%A Yi Bao
%A Wei Jiang
%A Bin Hong
%J BMC Microbiology
%D 2009
%I BioMed Central
%R 10.1186/1471-2180-9-14
%X Overexpression of sgcR3 in S. globisporus C-1027 resulted in a 30¨C40% increase in C-1027 production. Consistent with this, disruption of sgcR3 abolished C-1027 production. Complementation of the sgcR3-disrupted strain R3KO with intact sgcR3 gene could restore C-1027 production. The results from real time RT-PCR analysis in R3KO mutant and wild type strain indicated that not only transcripts of biosynthetic structural genes such as sgcA1 and sgcC4, but also putative regulatory genes, sgcR1 and sgcR2, were significantly decreased in R3KO mutant. The cross-complementation studies showed that sgcR1R2 could functionally complement sgcR3 disruption in trans. Purified N-terminal His10-tagged SgcR3 showed specific DNA-binding activity to the promoter region of sgcR1R2.The role of SgcR3 has been proved to be a positive regulator of C-1027 biosynthesis in S. globisporus C-1027. SgcR3 occupies a higher level than SgcR1 and SgcR2 in the regulatory hierarchy that controls C-1027 production and activates the transcription of sgcR1 and sgcR2 by binding directly to the promoter region of sgcR1R2.C-1027, also called lidamycin, is a chromoprotein antitumor antibiotic produced by Streptomyces globisporus C-1027 [1]. As a member of the enediyne family characterized by two acetylenic groups conjugated to a double bond within a 9- or 10-membered ring, C-1027 is 1,000 times more potent than adriamycin, one of the most effective chemotherapeutic agents [2]. C-1027 is a complex consisting of a 1:1 non-covalently associated mixture of an apoprotein and a 9-membered enediyne chromophore. The chromophore of the enediyne family can undergo a rearrangement to form a transient benzenoid diradical species that can abstract hydrogen atoms from DNA to initiate a cascade leading to DNA breaks, ultimately leading to cell death [3,4]. This novel mode of action has attracted great interest in developing these compounds into therapeutic agents for cancer. A CD33 monoclonal antibody (mAB)-calicheamicin (C
%U http://www.biomedcentral.com/1471-2180/9/14