Discovery of lucensimycins A and B from Streptomyces lucensis MA7349 using an antisense strategy.
Inhibition of protein synthesis is one of the validated and highly successful targets for inhibition of bacterial growth; this mechanism is a target of a large number of clinical drugs. Ribosomal protein S4, a primary protein, is a potential target for the discovery of antibacterial agents. We describe, using an antisense-sensitized rpsD Streptomyces aureus strain, the discovery and activity of lucensimycins A and B. [structure: see text].
Singh
Sheo B
SB
Merck Research Laboratories, Rahway, New Jersey 07065, USA. sheo_singh@merck.com
Zink
Deborah L
DL
Huber
Joanne
J
Genilloud
Olga
O
Salazar
Oscar
O
Diez
M Teresa
MT
Basilio
Angela
A
Vicente
Francisca
F
Byrne
Kevin M
KM
D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000494:pharmacology; D016373:DNA, Antisense / Q000235:genetics*; D004269:DNA, Bacterial / Q000235:genetics; D015195:Drug Design; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D013141:Spiro Compounds / Q000494:pharmacology; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D016373:DNA, Antisense; D004269:DNA, Bacterial; D013141:Spiro Compounds; C522747:lucensimycin A; C522748:lucensimycin B