Engineered Streptomyces platensis strains that overproduce antibiotics platensimycin and platencin.
Platensimycin, which is isolated from Streptomyces platensis MA7327, and platencin, which is isolated from S. platensis MA7339, are two recently discovered natural products that serve as important antibiotic leads. Here we report on 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/liter and 255 +/- 30 mg/liter, respectively. These results illustrate the effectiveness of genetic manipulation for the rational engineering of improvements in titers.
Smanski
Michael J
MJ
Division of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin-Madison, Madison, WI 53705-2222, USA.
Peterson
Ryan M
RM
Rajski
Scott R
SR
Shen
Ben
B
D000218:Adamantane / Q000378:metabolism*; D062365:Aminobenzoates / Q000378:metabolism*; D000627:Aminophenols / Q000378:metabolism*; D000813:Anilides / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D005285:Fermentation; D005818:Genetic Engineering; D006836:Hydro-Lyases / Q000235:genetics; D005810:Multigene Family; D011083:Polycyclic Compounds / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism*
D062365:Aminobenzoates; D000627:Aminophenols; D000813:Anilides; D000900:Anti-Bacterial Agents; D011083:Polycyclic Compounds; C111160:3-amino-5-hydroxybenzoic acid synthase; D006836:Hydro-Lyases; D000218:Adamantane; C510909:platensimycin; C520340:platencin