Coelomycin, a highly substituted 2,6-dioxo-pyrazine fungal metabolite antibacterial agent discovered by Staphylococcus aureus fitness test profiling.
Bacterial resistance to antibiotics, particularly to multiple antibiotics, is becoming a cause for significant concern. The only really viable course of action to counter this is to discover new antibiotics with novel modes of action. We have recently implemented a new antisense-based chemical genetic screening technology to accomplish this goal. The discovery and antibacterial activity of coelomycin, a fully substituted 2,6-dioxo pyrazine, illustrates the application of the Staphylococcus aureus fitness test strategy to natural products discovery.
Goetz
Michael A
MA
Merck Research Laboratories, Rahway, NJ 07065, USA.
Zhang
Chaowei
C
Zink
Deborah L
DL
Arocho
Marta
M
Vicente
Francisca
F
Bills
Gerald F
GF
Polishook
Jon
J
Dorso
Karen
K
Onishi
Russell
R
Gill
Charles
C
Hickey
Emily
E
Lee
Suzy
S
Ball
Richard
R
Skwish
Stephen
S
Donald
Robert G K
RG
Phillips
John W
JW
Singh
Sheo B
SB
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D001203:Ascomycota / Q000302:isolation & purification / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D018653:Juniperus / Q000382:microbiology; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011719:Pyrazines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000502:physiology*
D000900:Anti-Bacterial Agents; D011719:Pyrazines