PMID- 16562839
OWN - NLM
STAT- MEDLINE
DCOM- 20060508
LR  - 20131121
IS  - 0163-3864 (Print)
IS  - 0163-3864 (Linking)
VI  - 69
IP  - 3
DP  - 2006 Mar
TI  - Discovery of bacterial fatty acid synthase inhibitors from a Phoma species as 
      antimicrobial agents using a new antisense-based strategy.
PG  - 377-80
AB  - Fatty acids are essential for bacterial growth and viability, with the type II 
      fatty acid synthesis (FAS II) pathway being a potential antibacterial target. A 
      new, selective, and highly sensitive whole cell-based antisense strategy has been 
      designed to screen for natural product inhibitors of FabH/F of the FAS II pathway 
      using a high-throughput two-plate agar-based differential sensitivity assay 
      (FabF(2)p). An antisense assay along with the FASII enzyme prepared from 
      Staphylococcus aureus was used for bioactivity-guided fractionation, leading to 
      the isolation of phomallenic acids A-C (1-3) from a leaf litter fungus identified 
      as Phoma sp. Compounds 1-3 exhibited minimum detection concentrations (MDC) of 
      0.63, 0.31, and 0.15 microg/mL in the FabF(2P) assay, IC(50) values of 22, 3.4, 
      and 0.77 microg/mL in the FASII enzyme assay, and minimum inhibitory 
      concentrations (MIC) of 250, 7.8, and 3.9 microg/mL, respectively, against 
      wild-type S. aureus. Phomallenic acid C (3), the analogue with the longest chain, 
      exhibited the best overall activity within the phomallenic acids obtained and was 
      superior to cerulenin and thiolactomycin, the two most studied and commonly used 
      FabF inhibitors.
FAU - Ondeyka, John G
AU  - Ondeyka JG
AD  - Natural Products Chemistry and Medicinal Chemistry and Human and Animal 
      Infectious Diseases, Merck Research Laboratories, Merck & Co., Inc., Rahway, New 
      Jersey 07065, USA.
FAU - Zink, Deborah L
AU  - Zink DL
FAU - Young, Katherine
AU  - Young K
FAU - Painter, Ronald
AU  - Painter R
FAU - Kodali, Srinivas
AU  - Kodali S
FAU - Galgoci, Andrew
AU  - Galgoci A
FAU - Collado, Javier
AU  - Collado J
FAU - Tormo, Jose Ruben
AU  - Tormo JR
FAU - Basilio, Angela
AU  - Basilio A
FAU - Vicente, Francisca
AU  - Vicente F
FAU - Wang, Jun
AU  - Wang J
FAU - Singh, Sheo B
AU  - Singh SB
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Nat Prod
JT  - Journal of natural products
JID - 7906882
RN  - 0 (Alkadienes)
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Fatty Acids)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (Thiophenes)
RN  - 0 (phomallenic acid A)
RN  - 0 (phomallenic acid B)
RN  - 0 (phomallenic acid C)
RN  - 82079-32-1 (thiolactomycin)
RN  - EC 2.3.1.- (Acetyltransferases)
RN  - EC 2.3.1.85 (Fatty Acid Synthases)
RN  - EC 6.- (Fatty Acid Synthase, Type II)
SB  - IM
MH  - Acetyltransferases/*antagonists & inhibitors
MH  - *Alkadienes/chemistry/isolation & purification/pharmacology
MH  - *Anti-Bacterial Agents/chemistry/isolation & purification/pharmacology
MH  - Ascomycota/*chemistry
MH  - Fatty Acid Synthase, Type II
MH  - Fatty Acid Synthases/*antagonists & inhibitors
MH  - Fatty Acids/biosynthesis
MH  - France
MH  - Methicillin Resistance
MH  - Microbial Sensitivity Tests
MH  - Molecular Structure
MH  - Multienzyme Complexes/*antagonists & inhibitors
MH  - Staphylococcus aureus/*drug effects
MH  - Thiophenes/pharmacology
EDAT- 2006/03/28 09:00
MHDA- 2006/05/09 09:00
CRDT- 2006/03/28 09:00
PHST- 2006/03/28 09:00 [pubmed]
PHST- 2006/05/09 09:00 [medline]
PHST- 2006/03/28 09:00 [entrez]
AID - 10.1021/np050416w [doi]
PST - ppublish
SO  - J Nat Prod. 2006 Mar;69(3):377-80. doi: 10.1021/np050416w.