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Applied and Environmental Microbiology, April 2009, p. 2158-2165, Vol. 75, No. 7
0099-2240/09/$08.00+0     doi:10.1128/AEM.02209-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Characterization of rrdA, a TetR Family Protein Gene Involved in the Regulation of Secondary Metabolism in Streptomyces coelicolor{triangledown}

Xijun Ou,1 Bo Zhang,1 Lin Zhang,1 Guoping Zhao,1,2,3* and Xiaoming Ding1*

State Key Laboratory of Genetic Engineering, Department of Microbiology and Microbial Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China,1 Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Centre at Shanghai, Shanghai 201203, China,2 Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China3

Received 24 September 2008/ Accepted 28 January 2009

Streptomyces not only exhibits complex morphological differentiation but also produces a plethora of secondary metabolites, particularly antibiotics. To improve our general understanding of the complex network of undecylprodigiosin (Red) biosynthesis regulation, we used an in vivo transposition system to identify novel regulators that influence Red production in Streptomyces coelicolor M145. Using this screening system, we obtained 25 Red-deficient mutants. Twenty-four of these mutants had a transposon inserted in the previously described Red biosynthetic gene cluster and produced different amounts of another secondary metabolite, actinorhodin (Act). One mutant was shown to have an insertion in a different region of the chromosome upstream of the previously uncharacterized gene rrdA (regulator of redD, sco1104), which encodes a putative TetR family transcription factor. Compared with wild-type strain M145, the rrdA null mutant exhibited increased Red production and decreased Act production. A high level of rrdA expression resulted in a severe reduction in Red production and Act overproduction. Reverse transcription-PCR analysis showed that RrdA negatively regulated Red production by controlling redD mRNA abundance, while no change was observed at the transcript level of the Act-specific activator gene, actII-orf4. The effects on Act biosynthesis might arise from competition for precursors that are common to both pathways.


* Corresponding author. Mailing address: Department of Microbiology and Microbial Engineering, School of Life Sciences, Fudan University, 220 Handan Road, Shanghai 200433, China. Phone: 86 21 65643616. Fax: 86 21 65650149. E-mail for Xiaoming Ding: xmding74{at}fudan.edu.cn. E-mail for Guoping Zhao: gpzhao{at}sibs.ac.cn

{triangledown} Published ahead of print on 5 February 2009.


Applied and Environmental Microbiology, April 2009, p. 2158-2165, Vol. 75, No. 7
0099-2240/09/$08.00+0     doi:10.1128/AEM.02209-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.