AAC Accepts, published online ahead of print on 21 January 2009

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Antimicrob. Agents Chemother. doi:10.1128/AAC.01358-08
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Engineered Streptomyces platensis strains that overproduce antibiotics platensimycin and platencin

Michael J. Smanski, Ryan M. Peterson, Scott R. Rajski, and Ben Shen^*

Microbiology Doctoral Training Program, Division of Pharmaceutical Sciences, University of Wisconsin National Cooperative Drug Discovery Group, and Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA

^* To whom correspondence should be addressed. Email: bshen{at}pharmacy.wisc.edu.

Platensimycin, isolated from Streptomyces platensis MA7327, and platencin, isolated from S. platensis MA7339, are two recently discovered natural products that serve as important antibiotic leads. Here we report the identification of S. platensis MA7327 as a dual producer of both platensimycin and platencin. A PCR-based approach was used to locate and clone the locus involved in platensimycin and platencin production including ptmR1, which encodes a putative GntR-like transcriptional regulator. Deletion of this gene from the producing organism allowed us to isolate strains that overproduce platensimycin and platencin with yields of 323 ± 29 mg/L and 255 ± 30 mg/L, respectively. These results illustrate the effectiveness of genetic manipulation for the rational engineering of titer improvement.