Engineering of Streptomyces platensis MA7339 for overproduction of platencin and congeners.
Platensimycin (1) and platencin (2) are novel antibiotic leads against multidrug resistant pathogens. The production of 2 in Streptomyces platensis MA7339 is under the control of ptnR1, a GntR-like transcriptional regulator. Inactivating ptnR1 afforded S. platensis MA7339 mutant strain SB12600 that overproduces 2 at a titer approximately 100-fold greater than that from the wild-type strain and accumulates platencin A(1) (3) and eight new congeners, platencins A(2)-A(9) (4-11). The isolation, structural elucidation, and antibacterial activity of 4-11, in comparison to 1-3, are described.
Division of Pharmaceutical Sciences, University of Wisconsin, Madison, Wisconsin 53705, USA.
Zhiguo
Z
Yu
Michael J
MJ
Smanski
Ryan M
RM
Peterson
Karen
K
Marchillo
David
D
Andes
Scott R
SR
Rajski
Ben
B
Shen
D000627:Aminophenols / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D005818:Genetic Engineering / Q000379:methods*; D008826:Microbial Sensitivity Tests; D011083:Polycyclic Compounds / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism*
D000627:Aminophenols; D000900:Anti-Bacterial Agents; D011083:Polycyclic Compounds; C520340:platencin