The biosynthesis of the polyether antibiotic nanchangmycin is controlled by two pathway-specific transcriptional activat
- PDF / 665,019 Bytes
- 12 Pages / 595.276 x 790.866 pts Page_size
- 50 Downloads / 161 Views
ORIGINAL PAPER
The biosynthesis of the polyether antibiotic nanchangmycin is controlled by two pathway-specific transcriptional activators Qing Yu • Aiqin Du • Tiangang Liu Zixin Deng • Xinyi He
•
Received: 4 June 2011 / Revised: 28 September 2011 / Accepted: 24 October 2011 / Published online: 23 November 2011 Ó Springer-Verlag 2011
Abstract The nanchangmycin (NAN) produced by Streptomyces nanchangensis NS3226 is a polyether antibiotic resembling monensin in their gene clusters and the chemical structures. They can inhibit gram-positive bacteria and be a growth promoter for ruminants. Within the nanchangmycin gene cluster (nan), we identified that two SARP-family regulatory genes, nanR1 and nanR2, were both required to activate the transcription of all nan polyketide genes. Overexpression of NanR1 and NanR2 in wild-type increase NAN yields by at least three folds. Bioinformatic analysis of the immediate upstream DNA sequence of each nan gene and quantitative real-time RT-PCR analysis of the nan operons identified five putative SARP binding sites. Moreover, deletion of an AraC-family repressor gene nanR4 increased expression of NanR1 and R2 and led to a threefold increase in NAN production.
Communicated by Erko Stackebrandt.
Electronic supplementary material The online version of this article (doi:10.1007/s00203-011-0768-8) contains supplementary material, which is available to authorized users. Q. Yu A. Du T. Liu Z. Deng (&) X. He (&) State Key Laboratory of Microbial Metabolism, and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China e-mail: [email protected] X. He e-mail: [email protected] Present Address: T. Liu School of Pharmacy, Wuhan University, 185 Donghu Rd., Wuhan 430071, China
Keywords SARP Nanchangmycin Streptomyces Regulation
Introduction Actinomycetes continue to be prolific sources of novel secondary metabolites with diverse biological activities useful for human medicine and agriculture (Hopwood 2007). The production of secondary metabolites generally occurs in a growth phase-dependent manner (Bibb 1996). Most antibiotic production starts at the onset of the stationary growth phase both in submerged liquid cultures and on the grown agar surface (Gramajo et al. 1993). The antibiotic biosynthetic pathways are under the control of global and pathwayspecific regulators that respond to the changing nutrient status and other environmental conditions (Martin et al. 2011). Numerous hierarchical regulatory genes have been identified and studied in different antibiotic producing streptomycetes (Bibb 2005). Global regulators control the expression of multiple antibiotic biosynthetic clusters that may exist in one strain, and morphological differentiation (Champness and Chater 1994). For example, AdpA of Streptomyces griseus is triggered by the hormone-like molecule butyrolactone A-factor and plays a global role in the regulation of antibiotic biosynthesis and morphological development (Ohnishi et al. 2005). The pathway-specific
Data Loading...
