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PDBsum entry 2gfx
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Contents |
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* Residue conservation analysis
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Enzyme class:
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E.C.2.3.1.179
- beta-ketoacyl-[acyl-carrier-protein] synthase Ii.
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Reaction:
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(9Z)-hexadecenoyl-[ACP] + malonyl-[ACP] + H+ = 3-oxo-(11Z)- octadecenoyl-[ACP] + holo-[ACP] + CO2
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(9Z)-hexadecenoyl-[ACP]
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+
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malonyl-[ACP]
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+
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H(+)
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=
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3-oxo-(11Z)- octadecenoyl-[ACP]
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+
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holo-[ACP]
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+
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CO2
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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Nature
441:358-361
(2006)
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PubMed id:
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Platensimycin is a selective FabF inhibitor with potent antibiotic properties.
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J.Wang,
S.M.Soisson,
K.Young,
W.Shoop,
S.Kodali,
A.Galgoci,
R.Painter,
G.Parthasarathy,
Y.S.Tang,
R.Cummings,
S.Ha,
K.Dorso,
M.Motyl,
H.Jayasuriya,
J.Ondeyka,
K.Herath,
C.Zhang,
L.Hernandez,
J.Allocco,
A.Basilio,
J.R.Tormo,
O.Genilloud,
F.Vicente,
F.Pelaez,
L.Colwell,
S.H.Lee,
B.Michael,
T.Felcetto,
C.Gill,
L.L.Silver,
J.D.Hermes,
K.Bartizal,
J.Barrett,
D.Schmatz,
J.W.Becker,
D.Cully,
S.B.Singh.
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ABSTRACT
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Bacterial infection remains a serious threat to human lives because of emerging
resistance to existing antibiotics. Although the scientific community has avidly
pursued the discovery of new antibiotics that interact with new targets, these
efforts have met with limited success since the early 1960s. Here we report the
discovery of platensimycin, a previously unknown class of antibiotics produced
by Streptomyces platensis. Platensimycin demonstrates strong, broad-spectrum
Gram-positive antibacterial activity by selectively inhibiting cellular lipid
biosynthesis. We show that this anti-bacterial effect is exerted through the
selective targeting of beta-ketoacyl-(acyl-carrier-protein (ACP)) synthase I/II
(FabF/B) in the synthetic pathway of fatty acids. Direct binding assays show
that platensimycin interacts specifically with the acyl-enzyme intermediate of
the target protein, and X-ray crystallographic studies reveal that a specific
conformational change that occurs on acylation must take place before the
inhibitor can bind. Treatment with platensimycin eradicates Staphylococcus
aureus infection in mice. Because of its unique mode of action, platensimycin
shows no cross-resistance to other key antibiotic-resistant strains tested,
including methicillin-resistant S. aureus, vancomycin-intermediate S. aureus and
vancomycin-resistant enterococci. Platensimycin is the most potent inhibitor
reported for the FabF/B condensing enzymes, and is the only inhibitor of these
targets that shows broad-spectrum activity, in vivo efficacy and no observed
toxicity.
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Selected figure(s)
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Figure 1.
Figure 1: Characterization of platensimycin. a, Structure of
platensimycin. b, In vivo studies on platensimycin. Dosing at 50
 g
h^-1 showed small decrease in viable S. aureus cells from the
infected kidney. However, a 10^4–10^5 fold decrease (4 and 5
log reduction) were achieved with 100 and 150 g
h^-1, respectively. Dosing at 150 g
h^-1 showed 40% of the kidneys with no viable S. aureus, whereas
dosing at 100 g
h^-1 showed 20% of the kidneys without detectable viable S.
aureus. Error bars indicate s.d. observed with five infected
mice. The results were confirmed by a repeat experiment. c,
Whole-cell labelling assay^16 with platensimycin. The assay was
performed with a serial dilution of platensimycin, starting at
500 g
ml^-1. Platensimycin showed no significant inhibition against
syntheses of DNA (open circles), cell wall (filled triangles),
protein (open squares) and RNA (open triangles) but greatly
inhibited phospholipid synthesis (filled circles), providing an
IC[50] value of 0.1 g
ml^-1. Error bars indicate s.d. for three individual
experiments. d, Direct binding assay results of
[^3H]dihydroplatensimycin and E. coli FabF (ecFabF) in the
presence and absence of n-dodecanoyl coenzyme A (lauroyl-CoA;
C[12]-CoA) and the C163Q mutant protein. Error bars indicate
s.d. observed with six replicate wells. Experimental details are
given in Supplementary Information.
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Figure 2.
Figure 2: Interactions of platensimycin with ecFabF(C163Q) and
comparison with the apo structure. a, Superposition of
platensimycin (yellow, thicker sticks) on ecFabF, with
thiolactomycin (green) and cerulenin (cyan) shown for reference.
Side chains discussed in the text are labelled and coloured as
described above. The side chains from apo ecFabF are coloured
magenta. b, Interactions between the benzoic acid ring of
platensimycin (yellow) and ecFabF(C163Q). Side chains from the
protein discussed in the text are labelled and coloured green.
c, Interactions of ecFabF with the amide linker and ketolide of
platensimycin. The colour scheme is the same as in b. d, The
solvent-accessible surface area of FabF, coloured according to
electrostatic potential. Platensimycin is depicted as a stick
figure and coloured yellow, and is shown to be partly exposed to
solvent. Platensimycin buries 345 Å^2 of
solvent-accessible surface area on ecFabF, as calculated with
areaimol^24,25. Of that surface area, 122 Å^2 is a direct
result of the ketolide portion of the molecule, highlighting its
important contribution to platensimycin binding. Significant
interatomic distances (in ångströms) are marked in b
and c with red dashed lines and numbers.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(2006,
441,
358-361)
copyright 2006.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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A.S.Halavaty,
Y.Kim,
G.Minasov,
L.Shuvalova,
I.Dubrovska,
J.Winsor,
M.Zhou,
O.Onopriyenko,
T.Skarina,
L.Papazisi,
K.Kwon,
S.N.Peterson,
A.Joachimiak,
A.Savchenko,
and
W.F.Anderson
(2012).
Structural characterization and comparison of three acyl-carrier-protein synthases from pathogenic bacteria.
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Acta Crystallogr D Biol Crystallogr,
68,
1359-1370.
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PDB codes:
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A.Fabbretti,
C.O.Gualerzi,
and
L.Brandi
(2011).
How to cope with the quest for new antibiotics.
|
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FEBS Lett,
585,
1673-1681.
|
|
|
|
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|
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D.Awasthi,
K.Kumar,
and
I.Ojima
(2011).
Therapeutic potential of FtsZ inhibition: a patent perspective.
|
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Expert Opin Ther Pat,
21,
657-679.
|
|
|
|
|
|
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J.Liu,
D.Obando,
V.Liao,
T.Lifa,
and
R.Codd
(2011).
The many faces of the adamantyl group in drug design.
|
| |
Eur J Med Chem,
46,
1949-1963.
|
|
|
|
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J.Wang,
and
H.O.Sintim
(2011).
Dialkylamino-2,4-dihydroxybenzoic Acids as Easily Synthesized Analogues of Platensimycin and Platencin with Comparable Antibacterial Properties.
|
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Chemistry,
17,
3352-3357.
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M.Wu,
S.B.Singh,
J.Wang,
C.C.Chung,
G.Salituro,
B.V.Karanam,
S.H.Lee,
M.Powles,
K.P.Ellsworth,
M.E.Lassman,
C.Miller,
R.W.Myers,
M.R.Tota,
B.B.Zhang,
and
C.Li
(2011).
Antidiabetic and antisteatotic effects of the selective fatty acid synthase (FAS) inhibitor platensimycin in mouse models of diabetes.
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Proc Natl Acad Sci U S A,
108,
5378-5383.
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N.J.Singh,
D.Shin,
H.M.Lee,
H.T.Kim,
H.J.Chang,
J.M.Cho,
K.S.Kim,
and
S.Ro
(2011).
Structural basis of triclosan resistance.
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J Struct Biol,
174,
173-179.
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PDB codes:
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O.Genilloud,
I.González,
O.Salazar,
J.Martín,
J.R.Tormo,
and
F.Vicente
(2011).
Current approaches to exploit actinomycetes as a source of novel natural products.
|
| |
J Ind Microbiol Biotechnol,
38,
375-389.
|
|
|
|
|
|
|
R.Flavin,
G.Zadra,
and
M.Loda
(2011).
Metabolic alterations and targeted therapies in prostate cancer.
|
| |
J Pathol,
223,
283-294.
|
|
|
|
|
|
|
A.B.Castoreno,
Y.Smurnyy,
A.D.Torres,
M.S.Vokes,
T.R.Jones,
A.E.Carpenter,
and
U.S.Eggert
(2010).
Small molecules discovered in a pathway screen target the Rho pathway in cytokinesis.
|
| |
Nat Chem Biol,
6,
457-463.
|
|
|
|
|
|
|
A.Gurvitz
(2010).
Triclosan inhibition of mycobacterial InhA in Saccharomyces cerevisiae: yeast mitochondria as a novel platform for in vivo antimycolate assays.
|
| |
Lett Appl Microbiol,
50,
399-405.
|
|
|
|
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|
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C.A.Machutta,
G.R.Bommineni,
S.R.Luckner,
K.Kapilashrami,
B.Ruzsicska,
C.Simmerling,
C.Kisker,
and
P.J.Tonge
(2010).
Slow onset inhibition of bacterial beta-ketoacyl-acyl carrier protein synthases by thiolactomycin.
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J Biol Chem,
285,
6161-6169.
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D.C.Waalboer,
S.H.Leenders,
T.Schülin-Casonato,
F.L.van Delft,
and
F.P.Rutjes
(2010).
Total synthesis and antibiotic activity of dehydrohomoplatencin.
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Chemistry,
16,
11233-11236.
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D.I.Chan,
and
H.J.Vogel
(2010).
Current understanding of fatty acid biosynthesis and the acyl carrier protein.
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Biochem J,
430,
1.
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D.Wu,
X.D.Wu,
X.F.You,
X.F.Ma,
and
W.X.Tian
(2010).
Inhibitory effects on bacterial growth and beta-ketoacyl-ACP reductase by different species of maple leaf extracts and tannic acid.
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Phytother Res,
24,
S35-S41.
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H.Brötz-Oesterhelt,
and
P.Sass
(2010).
Postgenomic strategies in antibacterial drug discovery.
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Future Microbiol,
5,
1553-1579.
|
|
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|
|
|
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H.H.Xu,
J.D.Trawick,
R.J.Haselbeck,
R.A.Forsyth,
R.T.Yamamoto,
R.Archer,
J.Patterson,
M.Allen,
J.M.Froelich,
I.Taylor,
D.Nakaji,
R.Maile,
G.C.Kedar,
M.Pilcher,
V.Brown-Driver,
M.McCarthy,
A.Files,
D.Robbins,
P.King,
S.Sillaots,
C.Malone,
C.S.Zamudio,
T.Roemer,
L.Wang,
P.J.Youngman,
and
D.Wall
(2010).
Staphylococcus aureus TargetArray: comprehensive differential essential gene expression as a mechanistic tool to profile antibacterials.
|
| |
Antimicrob Agents Chemother,
54,
3659-3670.
|
|
|
|
|
|
|
H.Rahman,
B.Austin,
W.J.Mitchell,
P.C.Morris,
D.J.Jamieson,
D.R.Adams,
A.M.Spragg,
and
M.Schweizer
(2010).
Novel anti-infective compounds from marine bacteria.
|
| |
Mar Drugs,
8,
498-518.
|
|
|
|
|
|
|
I.Eleftheriadou,
N.Tentolouris,
V.Argiana,
E.Jude,
and
A.J.Boulton
(2010).
Methicillin-resistant Staphylococcus aureus in diabetic foot infections.
|
| |
Drugs,
70,
1785-1797.
|
|
|
|
|
|
|
J.J.La Clair
(2010).
Natural product mode of action (MOA) studies: a link between natural and synthetic worlds.
|
| |
Nat Prod Rep,
27,
969-995.
|
|
|
|
|
|
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K.Palanichamy,
and
K.P.Kaliappan
(2010).
Discovery and syntheses of "superbug challengers"-platensimycin and platencin.
|
| |
Chem Asian J,
5,
668-703.
|
|
|
|
|
|
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K.Tiefenbacher,
A.Gollner,
and
J.Mulzer
(2010).
Syntheses and antibacterial properties of iso-platencin, Cl-iso-platencin and Cl-platencin: identification of a new lead structure.
|
| |
Chemistry,
16,
9616-9622.
|
|
|
|
|
|
|
M.A.Beaulieu,
C.Sabot,
N.Achache,
K.C.Guérard,
and
S.Canesi
(2010).
An oxidative Prins-pinacol tandem process and its application to the synthesis of (-)-platensimycin.
|
| |
Chemistry,
16,
11224-11228.
|
|
|
|
|
|
|
M.A.Goetz,
C.Zhang,
D.L.Zink,
M.Arocho,
F.Vicente,
G.F.Bills,
J.Polishook,
K.Dorso,
R.Onishi,
C.Gill,
E.Hickey,
S.Lee,
R.Ball,
S.Skwish,
R.G.Donald,
J.W.Phillips,
and
S.B.Singh
(2010).
Coelomycin, a highly substituted 2,6-dioxo-pyrazine fungal metabolite antibacterial agent discovered by Staphylococcus aureus fitness test profiling.
|
| |
J Antibiot (Tokyo),
63,
512-518.
|
|
|
|
|
|
|
M.Bucci,
C.Goodman,
and
T.L.Sheppard
(2010).
A decade of chemical biology.
|
| |
Nat Chem Biol,
6,
847-854.
|
|
|
|
|
|
|
M.N.Gwynn,
A.Portnoy,
S.F.Rittenhouse,
and
D.J.Payne
(2010).
Challenges of antibacterial discovery revisited.
|
| |
Ann N Y Acad Sci,
1213,
5.
|
|
|
|
|
|
|
N.Koyama,
S.Kojima,
K.Nonaka,
R.Masuma,
M.Matsumoto,
S.Omura,
and
H.Tomoda
(2010).
Calpinactam, a new anti-mycobacterial agent, produced by Mortierella alpina FKI-4905.
|
| |
J Antibiot (Tokyo),
63,
183-186.
|
|
|
|
|
|
|
P.Li,
and
H.Yamamoto
(2010).
Formal synthesis of platencin.
|
| |
Chem Commun (Camb),
46,
6294-6295.
|
|
|
|
|
|
|
R.Flavin,
S.Peluso,
P.L.Nguyen,
and
M.Loda
(2010).
Fatty acid synthase as a potential therapeutic target in cancer.
|
| |
Future Oncol,
6,
551-562.
|
|
|
|
|
|
|
S.Donadio,
S.Maffioli,
P.Monciardini,
M.Sosio,
and
D.Jabes
(2010).
Antibiotic discovery in the twenty-first century: current trends and future perspectives.
|
| |
J Antibiot (Tokyo),
63,
423-430.
|
|
|
|
|
|
|
S.Nisa,
M.C.Blokpoel,
B.D.Robertson,
J.D.Tyndall,
S.Lun,
W.R.Bishai,
and
R.O'Toole
(2010).
Targeting the chromosome partitioning protein ParA in tuberculosis drug discovery.
|
| |
J Antimicrob Chemother,
65,
2347-2358.
|
|
|
|
|
|
|
V.Singh,
B.C.Sahu,
V.Bansal,
and
S.M.Mobin
(2010).
Intramolecular cycloaddition in 6,6-spiroepoxycyclohexa-2,4-dienone: simple aromatics to (+/-)-platencin.
|
| |
Org Biomol Chem,
8,
4472-4481.
|
|
|
|
|
|
|
W.Balemans,
N.Lounis,
R.Gilissen,
J.Guillemont,
K.Simmen,
K.Andries,
and
A.Koul
(2010).
Essentiality of FASII pathway for Staphylococcus aureus.
|
| |
Nature,
463,
E3; discussion E4.
|
|
|
|
|
|
|
X.Liu,
E.Ashforth,
B.Ren,
F.Song,
H.Dai,
M.Liu,
J.Wang,
Q.Xie,
and
L.Zhang
(2010).
Bioprospecting microbial natural product libraries from the marine environment for drug discovery.
|
| |
J Antibiot (Tokyo),
63,
415-422.
|
|
|
|
|
|
|
Y.Chen,
M.J.Smanski,
and
B.Shen
(2010).
Improvement of secondary metabolite production in Streptomyces by manipulating pathway regulation.
|
| |
Appl Microbiol Biotechnol,
86,
19-25.
|
|
|
|
|
|
|
Y.Du,
J.E.Gisselberg,
J.D.Johnson,
P.J.Lee,
S.T.Prigge,
and
B.O.Bachmann
(2010).
Lactococcus lactis fabH, encoding beta-ketoacyl-acyl carrier protein synthase, can be functionally replaced by the Plasmodium falciparum congener.
|
| |
Appl Environ Microbiol,
76,
3959-3966.
|
|
|
|
|
|
|
Y.Jiang,
R.M.Morgan-Kiss,
J.W.Campbell,
C.H.Chan,
and
J.E.Cronan
(2010).
Expression of Vibrio harveyi acyl-ACP synthetase allows efficient entry of exogenous fatty acids into the Escherichia coli fatty acid and lipid A synthetic pathways.
|
| |
Biochemistry,
49,
718-726.
|
|
|
|
|
|
|
Y.Shen,
J.Liu,
G.Estiu,
B.Isin,
Y.Y.Ahn,
D.S.Lee,
A.L.Barabási,
V.Kapatral,
O.Wiest,
and
Z.N.Oltvai
(2010).
Blueprint for antimicrobial hit discovery targeting metabolic networks.
|
| |
Proc Natl Acad Sci U S A,
107,
1082-1087.
|
|
|
|
|
|
|
Z.Yu,
M.J.Smanski,
R.M.Peterson,
K.Marchillo,
D.Andes,
S.R.Rajski,
and
B.Shen
(2010).
Engineering of Streptomyces platensis MA7339 for overproduction of platencin and congeners.
|
| |
Org Lett,
12,
1744-1747.
|
|
|
|
|
|
|
A.K.Barczak,
and
D.T.Hung
(2009).
Productive steps toward an antimicrobial targeting virulence.
|
| |
Curr Opin Microbiol,
12,
490-496.
|
|
|
|
|
|
|
A.K.Brown,
R.C.Taylor,
A.Bhatt,
K.Fütterer,
and
G.S.Besra
(2009).
Platensimycin activity against mycobacterial beta-ketoacyl-ACP synthases.
|
| |
PLoS One,
4,
e6306.
|
|
|
|
|
|
|
A.K.Ghosh,
and
K.Xi
(2009).
Total synthesis of (-)-platensimycin, a novel antibacterial agent.
|
| |
J Org Chem,
74,
1163-1170.
|
|
|
|
|
|
|
C.J.Zheng,
M.J.Sohn,
and
W.G.Kim
(2009).
Vinaxanthone, a new FabI inhibitor from Penicillium sp.
|
| |
J Antimicrob Chemother,
63,
949-953.
|
|
|
|
|
|
|
C.T.Walsh,
and
M.A.Fischbach
(2009).
Repurposing libraries of eukaryotic protein kinase inhibitors for antibiotic discovery.
|
| |
Proc Natl Acad Sci U S A,
106,
1689-1690.
|
|
|
|
|
|
|
C.Zhang,
J.G.Ondeyka,
D.L.Zink,
A.Basilio,
F.Vicente,
O.Salazar,
O.Genilloud,
K.Dorso,
M.Motyl,
K.Byrne,
and
S.B.Singh
(2009).
Discovery of okilactomycin and congeners from Streptomyces scabrisporus by antisense differential sensitivity assay targeting ribosomal protein S4.
|
| |
J Antibiot (Tokyo),
62,
55-61.
|
|
|
|
|
|
|
C.Zhang,
J.Ondeyka,
Z.Guan,
L.Dietrich,
B.Burgess,
J.Wang,
and
S.B.Singh
(2009).
Isolation, structure and biological activities of platensimycin B4 from Streptomyces platensis.
|
| |
J Antibiot (Tokyo),
62,
699-702.
|
|
|
|
|
|
|
G.D.Wright
(2009).
Making sense of antisense in antibiotic drug discovery.
|
| |
Cell Host Microbe,
6,
197-198.
|
|
|
|
|
|
|
H.Jayasuriya,
D.Zink,
A.Basilio,
F.Vicente,
J.Collado,
G.Bills,
M.L.Goldman,
M.Motyl,
J.Huber,
G.Dezeny,
K.Byrne,
and
S.B.Singh
(2009).
Discovery and antibacterial activity of glabramycin A-C from Neosartorya glabra by an antisense strategy.
|
| |
J Antibiot (Tokyo),
62,
265-269.
|
|
|
|
|
|
|
J.E.Bandow,
and
N.Metzler-Nolte
(2009).
New ways of killing the beast: prospects for inorganic-organic hybrid nanomaterials as antibacterial agents.
|
| |
Chembiochem,
10,
2847-2850.
|
|
|
|
|
|
|
K.C.Nicolaou,
G.S.Tria,
D.J.Edmonds,
and
M.Kar
(2009).
Total syntheses of (+/-)-platencin and (-)-platencin.
|
| |
J Am Chem Soc,
131,
15909-15917.
|
|
|
|
|
|
|
K.C.Nicolaou,
J.S.Chen,
D.J.Edmonds,
and
A.A.Estrada
(2009).
Recent advances in the chemistry and biology of naturally occurring antibiotics.
|
| |
Angew Chem Int Ed Engl,
48,
660-719.
|
|
|
|
|
|
|
K.C.Nicolaou,
J.S.Chen,
and
S.M.Dalby
(2009).
From nature to the laboratory and into the clinic.
|
| |
Bioorg Med Chem,
17,
2290-2303.
|
|
|
|
|
|
|
K.Shimamura,
H.Takahashi,
H.Kitazawa,
Y.Miyamoto,
A.Nagumo,
C.Tang,
D.Dean,
T.Nagase,
N.Sato,
and
S.Tokita
(2009).
Identification and characterization of a selective radioligand for ELOVL6.
|
| |
J Biochem,
146,
429-437.
|
|
|
|
|
|
|
M.A.Fischbach,
and
C.T.Walsh
(2009).
Antibiotics for emerging pathogens.
|
| |
Science,
325,
1089-1093.
|
|
|
|
|
|
|
M.J.Smanski,
R.M.Peterson,
S.R.Rajski,
and
B.Shen
(2009).
Engineered Streptomyces platensis strains that overproduce antibiotics platensimycin and platencin.
|
| |
Antimicrob Agents Chemother,
53,
1299-1304.
|
|
|
|
|
|
|
M.Patra,
G.Gasser,
A.Pinto,
K.Merz,
I.Ott,
J.E.Bandow,
and
N.Metzler-Nolte
(2009).
Synthesis and biological evaluation of chromium bioorganometallics based on the antibiotic platensimycin lead structure.
|
| |
ChemMedChem,
4,
1930-1938.
|
|
|
|
|
|
|
N.Nakashima,
and
T.Tamura
(2009).
Conditional gene silencing of multiple genes with antisense RNAs and generation of a mutator strain of Escherichia coli.
|
| |
Nucleic Acids Res,
37,
e103.
|
|
|
|
|
|
|
O.V.Barykina,
K.L.Rossi,
M.J.Rybak,
and
B.B.Snider
(2009).
Synthesis and antibacterial properties of (-)-nor-platencin.
|
| |
Org Lett,
11,
5334-5337.
|
|
|
|
|
|
|
P.J.Lee,
J.B.Bhonsle,
H.W.Gaona,
D.P.Huddler,
T.N.Heady,
M.Kreishman-Deitrick,
A.Bhattacharjee,
W.F.McCalmont,
L.Gerena,
M.Lopez-Sanchez,
N.E.Roncal,
T.H.Hudson,
J.D.Johnson,
S.T.Prigge,
and
N.C.Waters
(2009).
Targeting the fatty acid biosynthesis enzyme, beta-ketoacyl-acyl carrier protein synthase III (PfKASIII), in the identification of novel antimalarial agents.
|
| |
J Med Chem,
52,
952-963.
|
|
|
|
|
|
|
R.Pathania,
S.Zlitni,
C.Barker,
R.Das,
D.A.Gerritsma,
J.Lebert,
E.Awuah,
G.Melacini,
F.A.Capretta,
and
E.D.Brown
(2009).
Chemical genomics in Escherichia coli identifies an inhibitor of bacterial lipoprotein targeting.
|
| |
Nat Chem Biol,
5,
849-856.
|
|
|
|
|
|
|
S.Brinster,
G.Lamberet,
B.Staels,
P.Trieu-Cuot,
A.Gruss,
and
C.Poyart
(2009).
Type II fatty acid synthesis is not a suitable antibiotic target for Gram-positive pathogens.
|
| |
Nature,
458,
83-86.
|
|
|
|
|
|
|
S.R.Luckner,
C.A.Machutta,
P.J.Tonge,
and
C.Kisker
(2009).
Crystal structures of Mycobacterium tuberculosis KasA show mode of action within cell wall biosynthesis and its inhibition by thiolactomycin.
|
| |
Structure,
17,
1004-1013.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
S.Zlitni,
and
E.D.Brown
(2009).
Drug discovery: Not as fab as we thought.
|
| |
Nature,
458,
39-40.
|
|
|
|
|
|
|
X.Chen,
C.Burton,
X.Song,
L.McNamara,
A.Langella,
S.Cianetti,
C.H.Chang,
and
J.Wang
(2009).
An apoA-I mimetic peptide increases LCAT activity in mice through increasing HDL concentration.
|
| |
Int J Biol Sci,
5,
489-499.
|
|
|
|
|
|
|
X.Z.Li,
and
H.Nikaido
(2009).
Efflux-mediated drug resistance in bacteria: an update.
|
| |
Drugs,
69,
1555-1623.
|
|
|
|
|
|
|
A.R.Coates,
and
Y.Hu
(2008).
Targeting non-multiplying organisms as a way to develop novel antimicrobials.
|
| |
Trends Pharmacol Sci,
29,
143-150.
|
|
|
|
|
|
|
B.Bagautdinov,
Y.Ukita,
M.Miyano,
and
N.Kunishima
(2008).
Structure of 3-oxoacyl-(acyl-carrier protein) synthase II from Thermus thermophilus HB8.
|
| |
Acta Crystallogr Sect F Struct Biol Cryst Commun,
64,
358-366.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
C.Salmi,
C.Loncle,
N.Vidal,
Y.Letourneux,
J.Fantini,
M.Maresca,
N.Taïeb,
J.M.Pagès,
and
J.M.Brunel
(2008).
Squalamine: an appropriate strategy against the emergence of multidrug resistant gram-negative bacteria?
|
| |
PLoS ONE,
3,
e2765.
|
|
|
|
|
|
|
C.Zhang,
J.Ondeyka,
D.L.Zink,
B.Burgess,
J.Wang,
and
S.B.Singh
(2008).
Isolation, structure and fatty acid synthesis inhibitory activities of platensimycin B1-B3 from Streptomyces platensis.
|
| |
Chem Commun (Camb),
(),
5034-5036.
|
|
|
|
|
|
|
D.I.Chan,
T.Stockner,
D.P.Tieleman,
and
H.J.Vogel
(2008).
Molecular Dynamics Simulations of the Apo-, Holo-, and Acyl-forms of Escherichia coli Acyl Carrier Protein.
|
| |
J Biol Chem,
283,
33620-33629.
|
|
|
|
|
|
|
F.von Nussbaum,
S.Anlauf,
C.Freiberg,
J.Benet-Buchholz,
J.Schamberger,
T.Henkel,
G.Schiffer,
and
D.Häbich
(2008).
Total synthesis and initial structure-activity relationships of longicatenamycin A.
|
| |
ChemMedChem,
3,
619-626.
|
|
|
|
|
|
|
G.E.Schujman,
S.Altabe,
and
D.de Mendoza
(2008).
A malonyl-CoA-dependent switch in the bacterial response to a dysfunction of lipid metabolism.
|
| |
Mol Microbiol,
68,
987-996.
|
|
|
|
|
|
|
G.Parthasarathy,
R.Cummings,
J.W.Becker,
and
S.M.Soisson
(2008).
Surface-entropy reduction approaches to manipulate crystal forms of beta-ketoacyl acyl carrier protein synthase II from Streptococcus pneumoniae.
|
| |
Acta Crystallogr D Biol Crystallogr,
64,
141-148.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
J.Krauss,
V.Knorr,
V.Manhardt,
S.Scheffels,
and
F.Bracher
(2008).
Synthesis of platensimycin analogues and their antibiotic potency.
|
| |
Arch Pharm (Weinheim),
341,
386-392.
|
|
|
|
|
|
|
J.L.Guler,
E.Kriegova,
T.K.Smith,
J.Lukes,
and
P.T.Englund
(2008).
Mitochondrial fatty acid synthesis is required for normal mitochondrial morphology and function in Trypanosoma brucei.
|
| |
Mol Microbiol,
67,
1125-1142.
|
|
|
|
|
|
|
K.C.Nicolaou,
A.F.Stepan,
T.Lister,
A.Li,
A.Montero,
G.S.Tria,
C.I.Turner,
Y.Tang,
J.Wang,
R.M.Denton,
and
D.J.Edmonds
(2008).
Design, synthesis, and biological evaluation of platensimycin analogues with varying degrees of molecular complexity.
|
| |
J Am Chem Soc,
130,
13110-13119.
|
|
|
|
|
|
|
O.R.Sipahi
(2008).
Economics of antibiotic resistance.
|
| |
Expert Rev Anti Infect Ther,
6,
523-539.
|
|
|
|
|
|
|
P.Johansson,
B.Wiltschi,
P.Kumari,
B.Kessler,
C.Vonrhein,
J.Vonck,
D.Oesterhelt,
and
M.Grininger
(2008).
Inhibition of the fungal fatty acid synthase type I multienzyme complex.
|
| |
Proc Natl Acad Sci U S A,
105,
12803-12808.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
P.L.Taylor,
and
G.D.Wright
(2008).
Novel approaches to discovery of antibacterial agents.
|
| |
Anim Health Res Rev,
9,
237-246.
|
|
|
|
|
|
|
R.L.Lock,
and
E.J.Harry
(2008).
Cell-division inhibitors: new insights for future antibiotics.
|
| |
Nat Rev Drug Discov,
7,
324-338.
|
|
|
|
|
|
|
R.Pathania,
and
E.D.Brown
(2008).
Small and lethal: searching for new antibacterial compounds with novel modes of action.
|
| |
Biochem Cell Biol,
86,
111-115.
|
|
|
|
|
|
|
A.Pantosti,
A.Sanchini,
and
M.Monaco
(2007).
Mechanisms of antibiotic resistance in Staphylococcus aureus.
|
| |
Future Microbiol,
2,
323-334.
|
|
|
|
|
|
|
A.R.Coates,
and
Y.Hu
(2007).
Novel approaches to developing new antibiotics for bacterial infections.
|
| |
Br J Pharmacol,
152,
1147-1154.
|
|
|
|
|
|
|
B.Wilkinson,
and
J.Micklefield
(2007).
Mining and engineering natural-product biosynthetic pathways.
|
| |
Nat Chem Biol,
3,
379-386.
|
|
|
|
|
|
|
C.E.Christensen,
B.B.Kragelund,
P.von Wettstein-Knowles,
and
A.Henriksen
(2007).
Structure of the human beta-ketoacyl [ACP] synthase from the mitochondrial type II fatty acid synthase.
|
| |
Protein Sci,
16,
261-272.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
C.J.Balibar,
S.Garneau-Tsodikova,
and
C.T.Walsh
(2007).
Covalent CouN7 enzyme intermediate for acyl group shuttling in aminocoumarin biosynthesis.
|
| |
Chem Biol,
14,
679-690.
|
|
|
|
|
|
|
C.Qiao,
D.J.Wilson,
E.M.Bennett,
and
C.C.Aldrich
(2007).
A mechanism-based aryl carrier protein/thiolation domain affinity probe.
|
| |
J Am Chem Soc,
129,
6350-6351.
|
|
|
|
|
|
|
D.Braaten
(2007).
Bugs vs Drugs.
|
| |
Nat Med,
13,
522-523.
|
|
|
|
|
|
|
D.D.Baker,
M.Chu,
U.Oza,
and
V.Rajgarhia
(2007).
The value of natural products to future pharmaceutical discovery.
|
| |
Nat Prod Rep,
24,
1225-1244.
|
|
|
|
|
|
|
D.M.Byers,
and
H.Gong
(2007).
Acyl carrier protein: structure-function relationships in a conserved multifunctional protein family.
|
| |
Biochem Cell Biol,
85,
649-662.
|
|
|
|
|
|
|
G.C.Kedar,
V.Brown-Driver,
D.R.Reyes,
M.T.Hilgers,
M.A.Stidham,
K.J.Shaw,
J.Finn,
and
R.J.Haselbeck
(2007).
Evaluation of the metS and murB loci for antibiotic discovery using targeted antisense RNA expression analysis in Bacillus anthracis.
|
| |
Antimicrob Agents Chemother,
51,
1708-1718.
|
|
|
|
|
|
|
G.D.Wright,
and
A.D.Sutherland
(2007).
New strategies for combating multidrug-resistant bacteria.
|
| |
Trends Mol Med,
13,
260-267.
|
|
|
|
|
|
|
G.Pappenberger,
T.Schulz-Gasch,
E.Kusznir,
F.Müller,
and
M.Hennig
(2007).
Structure-assisted discovery of an aminothiazole derivative as a lead molecule for inhibition of bacterial fatty-acid synthesis.
|
| |
Acta Crystallogr D Biol Crystallogr,
63,
1208-1216.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
H.Jayasuriya,
K.Herath,
J.G.Ondeyka,
C.Zhang,
D.L.Zink,
M.Brower,
F.P.Gailliot,
J.Greene,
G.Birdsall,
J.Venugopal,
M.Ushio,
B.Burgess,
G.Russotti,
A.Walker,
M.Hesse,
A.Seeley,
B.Junker,
N.Connors,
O.Salazar,
O.Genilloud,
K.Liu,
P.Masurekar,
J.F.Barrett,
and
S.B.Singh
(2007).
Isolation and structure elucidation of thiazomycin- a potent thiazolyl peptide antibiotic from Amycolatopsis fastidiosa.
|
| |
J Antibiot (Tokyo),
60,
554-564.
|
|
|
|
|
|
|
H.T.Wright,
and
K.A.Reynolds
(2007).
Antibacterial targets in fatty acid biosynthesis.
|
| |
Curr Opin Microbiol,
10,
447-453.
|
|
|
|
|
|
|
J.L.Stephens,
S.H.Lee,
K.S.Paul,
and
P.T.Englund
(2007).
Mitochondrial fatty acid synthesis in Trypanosoma brucei.
|
| |
J Biol Chem,
282,
4427-4436.
|
|
|
|
|
|
|
J.Wang,
S.Kodali,
S.H.Lee,
A.Galgoci,
R.Painter,
K.Dorso,
F.Racine,
M.Motyl,
L.Hernandez,
E.Tinney,
S.L.Colletti,
K.Herath,
R.Cummings,
O.Salazar,
I.González,
A.Basilio,
F.Vicente,
O.Genilloud,
F.Pelaez,
H.Jayasuriya,
K.Young,
D.F.Cully,
and
S.B.Singh
(2007).
Discovery of platencin, a dual FabF and FabH inhibitor with in vivo antibiotic properties.
|
| |
Proc Natl Acad Sci U S A,
104,
7612-7616.
|
|
|
|
|
|
|
J.Z.Lu,
S.P.Muench,
M.Allary,
S.Campbell,
C.W.Roberts,
E.Mui,
R.L.McLeod,
D.W.Rice,
and
S.T.Prigge
(2007).
Type I and type II fatty acid biosynthesis in Eimeria tenella: enoyl reductase activity and structure.
|
| |
Parasitology,
134,
1949-1962.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
K.C.Nicolaou,
Y.Tang,
and
J.Wang
(2007).
Formal synthesis of (+/-)-platensimycin.
|
| |
Chem Commun (Camb),
(),
1922-1923.
|
|
|
|
|
|
|
K.L.Dormann,
and
R.Brückner
(2007).
Variable synthesis of the optically active thiotetronic acid antibiotics thiolactomycin, thiotetromycin, and 834-B1.
|
| |
Angew Chem Int Ed Engl,
46,
1160-1163.
|
|
|
|
|
|
|
K.Ohlsen,
and
U.Lorenz
(2007).
Novel targets for antibiotics in Staphylococcus aureus.
|
| |
Future Microbiol,
2,
655-666.
|
|
|
|
|
|
|
K.S.Lam
(2007).
New aspects of natural products in drug discovery.
|
| |
Trends Microbiol,
15,
279-289.
|
|
|
|
|
|
|
L.C.Rasmussen,
H.U.Sperling-Petersen,
and
K.K.Mortensen
(2007).
Hitting bacteria at the heart of the central dogma: sequence-specific inhibition.
|
| |
Microb Cell Fact,
6,
24.
|
|
|
|
|
|
|
M.Casenghi,
S.T.Cole,
and
C.F.Nathan
(2007).
New approaches to filling the gap in tuberculosis drug discovery.
|
| |
PLoS Med,
4,
e293.
|
|
|
|
|
|
|
M.Dermyer,
S.C.Wise,
T.Braden,
and
T.P.Holler
(2007).
Simultaneous screening of multiple bacterial tRNA synthetases using an Escherichia coli S30-based transcription and translation assay.
|
| |
Assay Drug Dev Technol,
5,
515-521.
|
|
|
|
|
|
|
M.Iwatsuki,
R.Uchida,
Y.Takakusagi,
A.Matsumoto,
C.L.Jiang,
Y.Takahashi,
M.Arai,
S.Kobayashi,
M.Matsumoto,
J.Inokoshi,
H.Tomoda,
and
S.Omura
(2007).
Lariatins, novel anti-mycobacterial peptides with a lasso structure, produced by Rhodococcus jostii K01-B0171.
|
| |
J Antibiot (Tokyo),
60,
357-363.
|
|
|
|
|
|
|
M.J.Llewelyn,
and
J.Cohen
(2007).
Tracking the microbes in sepsis: advancements in treatment bring challenges for microbial epidemiology.
|
| |
Clin Infect Dis,
44,
1343-1348.
|
|
|
|
|
|
|
M.J.Pucci
(2007).
Novel genetic techniques and approaches in the microbial genomics era: identification and/or validation of targets for the discovery of new antibacterial agents.
|
| |
Drugs R D,
8,
201-212.
|
|
|
|
|
|
|
M.M.Alhamadsheh,
F.Musayev,
A.A.Komissarov,
S.Sachdeva,
H.T.Wright,
N.Scarsdale,
G.Florova,
and
K.A.Reynolds
(2007).
Alkyl-CoA disulfides as inhibitors and mechanistic probes for FabH enzymes.
|
| |
Chem Biol,
14,
513-524.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
N.Dixon,
L.S.Wong,
T.H.Geerlings,
and
J.Micklefield
(2007).
Cellular targets of natural products.
|
| |
Nat Prod Rep,
24,
1288-1310.
|
|
|
|
|
|
|
P.Li,
J.N.Payette,
and
H.Yamamoto
(2007).
Enantioselective route to platensimycin: an intramolecular Robinson annulation approach.
|
| |
J Am Chem Soc,
129,
9534-9535.
|
|
|
|
|
|
|
S.B.Singh,
J.Occi,
H.Jayasuriya,
K.Herath,
M.Motyl,
K.Dorso,
C.Gill,
E.Hickey,
K.M.Overbye,
J.F.Barrett,
and
P.Masurekar
(2007).
Antibacterial evaluations of thiazomycin- a potent thiazolyl peptide antibiotic from Amycolatopsis fastidiosa.
|
| |
J Antibiot (Tokyo),
60,
565-571.
|
|
|
|
|
|
|
S.H.Lee,
J.L.Stephens,
and
P.T.Englund
(2007).
A fatty-acid synthesis mechanism specialized for parasitism.
|
| |
Nat Rev Microbiol,
5,
287-297.
|
|
|
|
|
|
|
S.Sridharan,
L.Wang,
A.K.Brown,
L.G.Dover,
L.Kremer,
G.S.Besra,
and
J.C.Sacchettini
(2007).
X-ray crystal structure of Mycobacterium tuberculosis beta-ketoacyl acyl carrier protein synthase II (mtKasB).
|
| |
J Mol Biol,
366,
469-480.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
U.Holzgrabe
(2007).
[Two flies with one blow--platencin, an new antibiotic]
|
| |
Pharm Unserer Zeit,
36,
418-419.
|
|
|
|
|
|
|
Y.Zou,
C.H.Chen,
C.D.Taylor,
B.M.Foxman,
and
B.B.Snider
(2007).
Formal synthesis of (+/-)-platensimycin.
|
| |
Org Lett,
9,
1825-1828.
|
|
|
|
|
|
|
A.P.Bhavsar,
and
E.D.Brown
(2006).
The worm turns for antimicrobial discovery.
|
| |
Nat Biotechnol,
24,
1098-1100.
|
|
|
|
|
|
|
C.Sheridan
(2006).
Antibiotics au naturel.
|
| |
Nat Biotechnol,
24,
1494-1496.
|
|
|
|
|
|
|
D.Häbich,
and
F.von Nussbaum
(2006).
Platensimycin, a new antibiotic and "superbug challenger" from nature.
|
| |
ChemMedChem,
1,
951-954.
|
|
|
|
|
|
|
D.I.Andersson
(2006).
The biological cost of mutational antibiotic resistance: any practical conclusions?
|
| |
Curr Opin Microbiol,
9,
461-465.
|
|
|
|
|
|
|
E.D.Brown
(2006).
Microbiology: antibiotic stops 'ping-pong' match.
|
| |
Nature,
441,
293-294.
|
|
|
|
|
|
|
F.E.Koehn
(2006).
Therapeutic potential of natural product signal transduction agents.
|
| |
Curr Opin Biotechnol,
17,
631-637.
|
|
|
|
|
|
|
J.Clardy,
M.A.Fischbach,
and
C.T.Walsh
(2006).
New antibiotics from bacterial natural products.
|
| |
Nat Biotechnol,
24,
1541-1550.
|
|
|
|
|
|
|
K.C.Nicolaou,
A.Li,
and
D.J.Edmonds
(2006).
Total synthesis of platensimycin.
|
| |
Angew Chem Int Ed Engl,
45,
7086-7090.
|
|
|
|
|
|
|
N.Nakashima,
T.Tamura,
and
L.Good
(2006).
Paired termini stabilize antisense RNAs and enhance conditional gene silencing in Escherichia coli.
|
| |
Nucleic Acids Res,
34,
e138.
|
|
|
|
|
|
|
P.Fernandes
(2006).
Antibacterial discovery and development--the failure of success?
|
| |
Nat Biotechnol,
24,
1497-1503.
|
|
|
|
|
|
|
U.Holzgrabe,
T.Dingermann,
and
I.Zündorf
(2006).
[An old pathway to new antibiotics--platensimycin]
|
| |
Pharm Unserer Zeit,
35,
388-389.
|
|
|
|
|
|
The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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|
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