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an ultra-long-chain di-unsaturated acyl-[acyl-carrier protein] + a malonyl-[acyl-carrier protein]
an ultra-long-chain di-unsaturated 3-oxo-fatty acyl-[acyl-carrier protein] + CO2 + an [acyl-carrier protein]
an ultra-long-chain di-unsaturated acyl-[acyl-carrier protein] + malonyl-[acyl-carrier protein AcpM]
an ultra-long-chain di-unsaturated 3-oxo-fatty acyl-[acyl-carrier protein] + CO2 + [acyl-carrier protein AcpM]
-
-
-
-
?
an ultra-long-chain di-unsaturated acyl-[acyl-carrier protein] + palmitoyl-[acyl-carrier protein AcpM]
an ultra-long-chain di-unsaturated 3-oxo-fatty acyl-[acyl-carrier protein] + CO2 + [acyl-carrier protein AcpM]
-
-
-
-
?
C12:0-[acyl-carrier protein from Escherichia coli] + malonyl-[acyl-carrier protein from Escherichia coli]
?
-
very low activity
-
-
?
C20:0-[acyl-carrier protein from Escherichia coli] + malonyl-[acyl-carrier protein from Escherichia coli]
?
-
very low activity
-
-
?
C4:0-[acyl-carrier protein from Escherichia coli] + malonyl-[acyl-carrier protein from Escherichia coli]
?
-
very low activity
-
-
?
lauroyl-CoA + malonyl-CoA
?
-
2% activity compared to lauroyl-[acyl-carrier protein from Escherichia coli] plus malonyl-[acyl-carrier protein from Escherichia coli]
-
-
?
lauroyl-CoA + malonyl-phosphopantetheine
?
-
1% activity compared to lauroyl-[acyl-carrier protein from Escherichia coli] plus malonyl-[acyl-carrier protein from Escherichia coli]
-
-
?
lauroyl-CoA + malonyl-phosphopantetheine 14-mer
?
-
108% activity compared to lauroyl-[acyl-carrier protein from Escherichia coli] plus malonyl-[acyl-carrier protein from Escherichia coli]
-
-
?
lauroyl-CoA + malonyl-phosphopantetheine 16-mer
?
-
100% activity compared to lauroyl-[acyl-carrier protein from Escherichia coli] plus malonyl-[acyl-carrier protein from Escherichia coli]
-
-
?
lauroyl-CoA + malonyl-phosphopantetheine 8-mer
?
-
22% activity compared to lauroyl-[acyl-carrier protein from Escherichia coli] plus malonyl-[acyl-carrier protein from Escherichia coli]
-
-
?
lauroyl-[acyl-carrier protein from Escherichia coli] + malonyl-[acyl-carrier protein from Escherichia coli]
?
-
100% activity
-
-
?
myristoyl-[acyl-carrier protein] + biotinylated malonyl-[acyl-carrier protein]
?
-
-
-
-
?
palmitoyl-CoA + a malonyl-[acyl-carrier protein]
?
palmitoyl-CoA + malonyl-[acyl-carrier protein AcpM]
?
palmitoyl-CoA + malonyl-[acyl-carrier protein from Escherichia coli]
?
-
weak activity
-
-
?
palmitoyl-[acyl-carrier protein from Escherichia coli] + malonyl-[acyl-carrier protein from Escherichia coli]
?
-
best substrate
-
-
?
palmitoyl-[acyl-carrier protein M] + malonyl-[acyl-carrier protein M]
?
additional information
?
-
an ultra-long-chain di-unsaturated acyl-[acyl-carrier protein] + a malonyl-[acyl-carrier protein]
an ultra-long-chain di-unsaturated 3-oxo-fatty acyl-[acyl-carrier protein] + CO2 + an [acyl-carrier protein]
-
the enzyme synthesizes longer multi-unsaturated acyl chains averaging 54 carbons units
-
-
?
an ultra-long-chain di-unsaturated acyl-[acyl-carrier protein] + a malonyl-[acyl-carrier protein]
an ultra-long-chain di-unsaturated 3-oxo-fatty acyl-[acyl-carrier protein] + CO2 + an [acyl-carrier protein]
-
-
-
-
?
an ultra-long-chain di-unsaturated acyl-[acyl-carrier protein] + a malonyl-[acyl-carrier protein]
an ultra-long-chain di-unsaturated 3-oxo-fatty acyl-[acyl-carrier protein] + CO2 + an [acyl-carrier protein]
-
C38-C42
-
-
?
an ultra-long-chain di-unsaturated acyl-[acyl-carrier protein] + a malonyl-[acyl-carrier protein]
an ultra-long-chain di-unsaturated 3-oxo-fatty acyl-[acyl-carrier protein] + CO2 + an [acyl-carrier protein]
-
C38-C42
-
-
?
an ultra-long-chain di-unsaturated acyl-[acyl-carrier protein] + a malonyl-[acyl-carrier protein]
an ultra-long-chain di-unsaturated 3-oxo-fatty acyl-[acyl-carrier protein] + CO2 + an [acyl-carrier protein]
-
-
-
-
?
palmitoyl-CoA + a malonyl-[acyl-carrier protein]
?
-
-
-
-
?
palmitoyl-CoA + a malonyl-[acyl-carrier protein]
?
-
-
-
-
?
palmitoyl-CoA + malonyl-[acyl-carrier protein AcpM]
?
-
-
-
-
?
palmitoyl-CoA + malonyl-[acyl-carrier protein AcpM]
?
-
-
-
-
?
palmitoyl-[acyl-carrier protein M] + malonyl-[acyl-carrier protein M]
?
-
-
-
-
?
palmitoyl-[acyl-carrier protein M] + malonyl-[acyl-carrier protein M]
?
-
-
-
-
?
additional information
?
-
-
the beta-ketoacyl acyl carrier protein synthase II is a mycobacterial elongation condensing enzyme involved in FAS-II, FAS-II is considered to elongate medium chain length fatty acyl primers to provide long chain, C56, precursors of mycolic acids, mycolic acids are long chain alpha-alkyl branched, beta-hydroxy fatty acids that represent a characteristic component of the Mycobacterium tuberculosis cell wall
-
-
?
additional information
?
-
-
the enzyme catalyzes the Claisen-type condensation reaction
-
-
?
additional information
?
-
-
the beta-ketoacyl acyl carrier protein synthase II is a mycobacterial elongation condensing enzyme involved in FAS-II, FAS-II is considered to elongate medium chain length fatty acyl primers to provide long chain, C56, precursors of mycolic acids, mycolic acids are long chain alpha-alkyl branched, beta-hydroxy fatty acids that represent a characteristic component of the Mycobacterium tuberculosis cell wall
-
-
?
additional information
?
-
-
the enzyme catalyzes the Claisen-type condensation reaction
-
-
?
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an ultra-long-chain di-unsaturated acyl-[acyl-carrier protein] + a malonyl-[acyl-carrier protein]
an ultra-long-chain di-unsaturated 3-oxo-fatty acyl-[acyl-carrier protein] + CO2 + an [acyl-carrier protein]
an ultra-long-chain di-unsaturated acyl-[acyl-carrier protein] + malonyl-[acyl-carrier protein AcpM]
an ultra-long-chain di-unsaturated 3-oxo-fatty acyl-[acyl-carrier protein] + CO2 + [acyl-carrier protein AcpM]
-
-
-
-
?
an ultra-long-chain di-unsaturated acyl-[acyl-carrier protein] + palmitoyl-[acyl-carrier protein AcpM]
an ultra-long-chain di-unsaturated 3-oxo-fatty acyl-[acyl-carrier protein] + CO2 + [acyl-carrier protein AcpM]
-
-
-
-
?
additional information
?
-
an ultra-long-chain di-unsaturated acyl-[acyl-carrier protein] + a malonyl-[acyl-carrier protein]
an ultra-long-chain di-unsaturated 3-oxo-fatty acyl-[acyl-carrier protein] + CO2 + an [acyl-carrier protein]
-
the enzyme synthesizes longer multi-unsaturated acyl chains averaging 54 carbons units
-
-
?
an ultra-long-chain di-unsaturated acyl-[acyl-carrier protein] + a malonyl-[acyl-carrier protein]
an ultra-long-chain di-unsaturated 3-oxo-fatty acyl-[acyl-carrier protein] + CO2 + an [acyl-carrier protein]
-
-
-
-
?
an ultra-long-chain di-unsaturated acyl-[acyl-carrier protein] + a malonyl-[acyl-carrier protein]
an ultra-long-chain di-unsaturated 3-oxo-fatty acyl-[acyl-carrier protein] + CO2 + an [acyl-carrier protein]
-
C38-C42
-
-
?
an ultra-long-chain di-unsaturated acyl-[acyl-carrier protein] + a malonyl-[acyl-carrier protein]
an ultra-long-chain di-unsaturated 3-oxo-fatty acyl-[acyl-carrier protein] + CO2 + an [acyl-carrier protein]
-
C38-C42
-
-
?
an ultra-long-chain di-unsaturated acyl-[acyl-carrier protein] + a malonyl-[acyl-carrier protein]
an ultra-long-chain di-unsaturated 3-oxo-fatty acyl-[acyl-carrier protein] + CO2 + an [acyl-carrier protein]
-
-
-
-
?
additional information
?
-
-
the beta-ketoacyl acyl carrier protein synthase II is a mycobacterial elongation condensing enzyme involved in FAS-II, FAS-II is considered to elongate medium chain length fatty acyl primers to provide long chain, C56, precursors of mycolic acids, mycolic acids are long chain alpha-alkyl branched, beta-hydroxy fatty acids that represent a characteristic component of the Mycobacterium tuberculosis cell wall
-
-
?
additional information
?
-
-
the beta-ketoacyl acyl carrier protein synthase II is a mycobacterial elongation condensing enzyme involved in FAS-II, FAS-II is considered to elongate medium chain length fatty acyl primers to provide long chain, C56, precursors of mycolic acids, mycolic acids are long chain alpha-alkyl branched, beta-hydroxy fatty acids that represent a characteristic component of the Mycobacterium tuberculosis cell wall
-
-
?
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malfunction
-
an inactive enzyme-deficient mutant has less density of mycolic acid, embedded in periplasmic space, with normal thickness in the cell envelope, which results in loss of acid-fastness
malfunction
-
enzyme gene deletion in Mycobacterium tuberculosis causes loss of acid-fastness and subclinical latent tuberculosis in immunocompetent mice. An additional outcome of enzyme gene deletion is the loss of ketomycolic acid trans-cyclopropanation and a drastic reduction in methoxymycolic acid trans-cyclopropanation. Although deletion of the enzyme also markedly alters the colony morphology and abolishes classic serpentine growth (cording), the most profound effect of enzyme gene deletion is the ability of the mutant strain to persist in infected immunocompetent mice for up to 600 days without causing disease or mortality
malfunction
-
enzyme mutants exhibit strikingly altered cell wall permeability, leading to a marked increase in susceptibility to lipophilic antibiotics and the host antimicrobial molecules defensing and lysozyme. The predominant chain lengths are 2-4 carbons shorter for oxygenated mycolates in the absence of the enzyme
malfunction
-
an inactive enzyme-deficient mutant has less density of mycolic acid, embedded in periplasmic space, with normal thickness in the cell envelope, which results in loss of acid-fastness
-
malfunction
-
enzyme mutants exhibit strikingly altered cell wall permeability, leading to a marked increase in susceptibility to lipophilic antibiotics and the host antimicrobial molecules defensing and lysozyme. The predominant chain lengths are 2-4 carbons shorter for oxygenated mycolates in the absence of the enzyme
-
metabolism
-
the enzyme can catalyze both saturated and unsaturated fatty acid biosynthesis
metabolism
-
the enzyme is involved in fatty acid and mycolic acid biosynthesis
metabolism
-
when enzyme KasB is coexpressed with KasA, it appears to be capable of facilitating the production of lipids of the length of full meromycolic acids. KasB therefore may accept primers directly from KasA that average 40 carbons in length. KasA and KasB thus function in tandem to carrier out acyl chain elongation to achieve meromycolic acid synthesis from acyl primers provided by type I fatty acid synthase system
metabolism
-
the enzyme is involved in fatty acid and mycolic acid biosynthesis
-
metabolism
-
when enzyme KasB is coexpressed with KasA, it appears to be capable of facilitating the production of lipids of the length of full meromycolic acids. KasB therefore may accept primers directly from KasA that average 40 carbons in length. KasA and KasB thus function in tandem to carrier out acyl chain elongation to achieve meromycolic acid synthesis from acyl primers provided by type I fatty acid synthase system
-
physiological function
-
enzyme-dependent mycolate elongation is essential for cording and cell wall impermeability. Enzyme-dependent cell wall impermeability is essential for antibiotic resistance. The enzyme is essential for resistance to macrophage antimicrobial activity
physiological function
-
the enzyme is involved in cording and acid-fast staining and is required for survival and virulence in infected mice
physiological function
-
enzyme-dependent mycolate elongation is essential for cording and cell wall impermeability. Enzyme-dependent cell wall impermeability is essential for antibiotic resistance. The enzyme is essential for resistance to macrophage antimicrobial activity
-
physiological function
-
the enzyme is involved in cording and acid-fast staining and is required for survival and virulence in infected mice
-
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Sridharan, S.; Wang, L.; Brown, A.K.; Dover, L.G.; Kremer, L.; Besra, G.S.; Sacchettini, J.C.
X-ray crystal structure of Mycobacterium tuberculosis beta-ketoacyl acyl carrier protein synthase II (mtKasB)
J. Mol. Biol.
366
469-480
2007
Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv
brenda
Borgaro, J.; Chang, A.; MacHutta, C.; Zhang, X.; Tonge, P.
Substrate recognition by beta-ketoacyl-ACP synthases
Biochemistry
50
10678-10686
2011
Escherichia coli
brenda
Kremer, L.; Douglas, J.D.; Baulard, A.R.; Morehouse, C.; Guy, M.R.; Alland, D.; Dover, L.G.; Lakey, J.H.; Jacobs, W.R.; Brennan, P.J.; Minnikin, D.E.; Besra, G.S.
Thiolactomycin and related analogues as novel anti-mycobacterial agents targeting KasA and KasB condensing enzymes in Mycobacterium tuberculosis
J. Biol. Chem.
275
16857-16864
2000
Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv
brenda
Schaeffer, M.L.; Agnihotri, G.; Volker, C.; Kallender, H.; Brennan, P.J.; Lonsdale, J.T.
Purification and biochemical characterization of the Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein synthases KasA and KasB
J. Biol. Chem.
276
47029-47037
2001
Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv
brenda
Molle, V.; Brown, A.; Besra, G.; Cozzone, A.; Kremer, L.
The condensing activities of the Mycobacterium tuberculosis type II fatty acid synthase are differentially regulated by phosphorylation
J. Biol. Chem.
281
30094-30103
2006
Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv
brenda
Machutta, C.A.; Bommineni, G.R.; Luckner, S.R.; Kapilashrami, K.; Ruzsicska, B.; Simmerling, C.; Kisker, C.; Tonge, P.J.
Slow onset inhibition of bacterial beta-ketoacyl-acyl carrier protein synthases by thiolactomycin
J. Biol. Chem.
285
6161-6169
2010
Mycobacterium tuberculosis
brenda
Sridharan, S.; Wang, L.; Brown, A.; Dover, L.; Kremer, L.; Besra, G.; Sacchettini, J.
X-ray crystal structure of Mycobacterium tuberculosis beta-ketoacyl acyl carrier protein synthase II (mtKasB)
J. Mol. Biol.
366
469-480
2007
Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv
brenda
Gao, L.Y.; Laval, F.; Lawson, E.H.; Groger, R.K.; Woodruff, A.; Morisaki, J.H.; Cox, J.S.; Daffe, M.; Brown, E.J.
Requirement for kasB in Mycobacterium mycolic acid biosynthesis, cell wall impermeability and intracellular survival implications for therapy
Mol. Microbiol.
49
1547-1563
2003
Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv
brenda
Bhatt, A.; Molle, V.; Besra, G.; Jacobs Jr., W.; Kremer, L.
The Mycobacterium tuberculosis FAS-II condensing enzymes Their role in mycolic acid biosynthesis, acid-fastness, pathogenesis and in future drug development
Mol. Microbiol.
64
1442-1454
2007
Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv
brenda
Vilcheze, C.; Molle, V.; Carrere-Kremer, S.; Leiba, J.; Mourey, L.; Shenai, S.; Baronian, G.; Tufariello, J.; Hartman, T.; Veyron-Churlet, R.; Trivelli, X.; Tiwari, S.; Weinrick, B.; Alland, D.; Guerardel, Y.; Jacobs Jr., W.; Kremer, L.
Phosphorylation of KasB regulates virulence and acid-fastness in Mycobacterium tuberculosis
PLoS Pathog.
10
e1004115
2014
Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv
brenda
Bhatt, A.; Fujiwara, N.; Bhatt, K.; Gurcha, S.S.; Kremer, L.; Chen, B.; Chan, J.; Porcelli, S.A.; Kobayashi, K.; Besra, G.S.; Jacobs, W.R.
Deletion of kasB in Mycobacterium tuberculosis causes loss of acid-fastness and subclinical latent tuberculosis in immunocompetent mice
Proc. Natl. Acad. Sci. USA
104
5157-5162
2007
Mycobacterium tuberculosis
brenda
Slayden, R.; Barry III, C.
The role of KasA and KasB in the biosynthesis of meromycolic acids and isoniazid resistance in Mycobacterium tuberculosis
Tuberculosis
82
149-160
2002
Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv
brenda
Schaeffer, M.L.; Carson, J.D.; Kallender, H.; Lonsdale, J.T.
Development of a scintillation proximity assay for the Mycobacterium tuberculosis KasA and KasB enzymes involved in mycolic acid biosynthesis
Tuberculosis
84
353-360
2004
Mycobacterium tuberculosis
brenda
Yamada, H.; Bhatt, A.; Danev, R.; Fujiwara, N.; Maeda, S.; Mitarai, S.; Chikamatsu, K.; Aono, A.; Nitta, K.; Jacobs Jr., W.; Nagayama, K.
Non-acid-fastness in Mycobacterium tuberculosis DELTAkasB mutant correlates with the cell envelope electron density
Tuberculosis
92
351-357
2012
Mycobacterium tuberculosis, Mycobacterium tuberculosis CDC1551
brenda