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3-ketoacyl reductase

The reaction is catalyzed by the fourth synthetase enzyme- P-ketoacyl reductase, to yield intermediary hydroxybutyryl. [Pg.202]

ACP acyl carrier protein AT acyltransferase DH dehydratase ER enoyl reductase KR p-ketoacyl reductase KS p-ketoacyl synthase TE thioesterase... [Pg.115]

Figure 3 The fatty acid biosynthetic cycle (ACP, acyl carrier protein KS, P-ketoacyl synthase KR, P-ketoacyl reductase DH, dehydratase ER, enoyl reductase TE, thioes-terase). Figure 3 The fatty acid biosynthetic cycle (ACP, acyl carrier protein KS, P-ketoacyl synthase KR, P-ketoacyl reductase DH, dehydratase ER, enoyl reductase TE, thioes-terase).
Figure 5 Domain organization of the erythromycin polyketide synthase. Putative domains are represented as circles and the structural residues are ignored. Each module incorporates the essential KS, AT, and ACP domains, while all but one include optional reductive activities. AT, acyltransferase ACP, acyl carrier protein KS, (3-ketoacyl synthase KR, P-ketoacyl reductase DH, dehydratase ER, enoyl reductase TE, thioesterase. Figure 5 Domain organization of the erythromycin polyketide synthase. Putative domains are represented as circles and the structural residues are ignored. Each module incorporates the essential KS, AT, and ACP domains, while all but one include optional reductive activities. AT, acyltransferase ACP, acyl carrier protein KS, (3-ketoacyl synthase KR, P-ketoacyl reductase DH, dehydratase ER, enoyl reductase TE, thioesterase.
H Wong, JS Mattick, SJ Wakil. The architecture of the animal fatty acid synthetase. III. Isolation and characterisation of (3-ketoacyl reductase. JBiol Chem 258 15305-15311, 1983. [Pg.469]

The / -keto esters are reduced to the respective chiral ft -hydroxy esters by at least two alternative enzymes one of which is D-directing the other one is L-directing (Fig. 3.4). A product mixture results that contains both enantiomeric forms, d and i.,b of the carbinol (/1-hydroxy ester) in varying degrees. In the case of ethyl acetoacetate (1) preferably the L-form of ethyl 3-hydroxybutyrate (l-4) is produced which is then secreted from the cell [55-58]. The L-directing enzyme is methyl butyralde-hyde reductase (MBAR EC 1.1.1.265), and the D-enantiomer is formed by the action of /J-ketoacyl reductase (KAR EC 1.1.1.100) which is a constituent of fatty acid anabolism (Fig. 3.4) [49, 59]. Alcohol dehydrogenase (ADH EC 1.1.1.1) L-directing activity is classically attributed to was shown to be inactive - moreover the enzyme is even inhibited by the substrate [2, 34, 37]. [Pg.69]

This was nicely outlined with the observed unusually high enantiopurity of the dehalogenation consecutive product ethyl L-3-hydroxybutyrate (l-4 Pathways II, III). Ester hydrolysis product 16 acts as an inhibitor of D-directing /3-ketoacyl reductase of the fatty acid synthase (FAS) complex (EC 1.1.1.100) [69, 70], whereupon the fraction of l-4 increased from 97% ee to >99.5% ee. [Pg.74]

Especially the NADPH-dependent yS-ketoacyl-reductase domains KRl and KR2, which synthesize 5-(R) and 3-(S)-configured /ff-hydroxy-acylthioester building blocks, respectively, were intensively used to study the impact of genetic manipulations [8 -11J. [Pg.345]

Fig. 4. X-ray determined protein crystal structures of multienzyme ensembly lines, (a) Mammalian fatty acid synthase at 4.5 A resolution (PDB 2cf2). Domain organization A starter substrate, acetyl-CoA or malonyl-CoA, gets loaded onto the acyl-carrler protein (ACP/absent in the structure) via the malonyl-CoA-/acetyl-CoA-ACP transacylase (MAT). Then, the ketoacyl synthase (KS) catalyzes a decarboxylative condensation reaction and forms the B-ketoacyl-ACP. This is followed from a reduction reaction catalyzed by the B-ketoacyl reductase (KR). Subsequently, the Intermediate gets dehydrated by a dehydratase (DH) and additionally reduced by a B-enoyl reductase (ER). The product gets released from the ACP by a thloesterase (absent in the structure), (b) Module 3 of 6-deoxyerthronolide B synthase at 2.6 A resolution (PDB 2qo3) bound to the inhibitor cerulin. The ketosynthase (KS) - acyltransferase (AT) di-domain is part of the large homodimeric polypeptide involved in biosynthesis of erythromycin from Saccharopolyspora erythraea... Fig. 4. X-ray determined protein crystal structures of multienzyme ensembly lines, (a) Mammalian fatty acid synthase at 4.5 A resolution (PDB 2cf2). Domain organization A starter substrate, acetyl-CoA or malonyl-CoA, gets loaded onto the acyl-carrler protein (ACP/absent in the structure) via the malonyl-CoA-/acetyl-CoA-ACP transacylase (MAT). Then, the ketoacyl synthase (KS) catalyzes a decarboxylative condensation reaction and forms the B-ketoacyl-ACP. This is followed from a reduction reaction catalyzed by the B-ketoacyl reductase (KR). Subsequently, the Intermediate gets dehydrated by a dehydratase (DH) and additionally reduced by a B-enoyl reductase (ER). The product gets released from the ACP by a thloesterase (absent in the structure), (b) Module 3 of 6-deoxyerthronolide B synthase at 2.6 A resolution (PDB 2qo3) bound to the inhibitor cerulin. The ketosynthase (KS) - acyltransferase (AT) di-domain is part of the large homodimeric polypeptide involved in biosynthesis of erythromycin from Saccharopolyspora erythraea...
The activities involved in yeast fatty acid biosynthesis are covalently linked as separate domains of two multifunctional polypeptides, a and p, encoded by the fas2 and fasl genes, respectively (Fig. 2) [57,58]. The functionalities associated with the 220 kDa a subunit include -ketoacyl synthase activity, -ketoacyl reductase activity, and an AGP domain which bears a phosphopantetheinylated serine. The 208 kDa -subunit has acetyl and malonyl CoA transacylase, palmi-toyl transferase, -hydroxyacyl-enzyme dehydratase, and enoyl acyl-enzyme reductase activities. The two subunits can be readily dissociated, and the individual activities maybe measured [57]. [Pg.94]

Figure 22.23. Schematic Representation of Animal Fatty Acid Synthase. Each of the identical chains in the dimer contains three domains. Domain 1 (blue) contains acetyl transferase (AT), malonyl transferase (MT), and condensing enzyme (CE). Domain 2 (yellow) contains acyl carrier protein (ACP), P-ketoacyl reductase (KR), dehydratase (DH), and enoyl reductase (ER). Domain 3 (red) contains thioesterase (TE). The flexible phosphopantetheinyl group (green) carries the fatty acyl chain from one catalytic site on a chain to another, as well as between chains in the dimer. [After Y. Tsukamoto, H. Wong, J. S. Mattick, and S. J. Wakil. J. Biol. Chem. 258(1983) 15312.]... Figure 22.23. Schematic Representation of Animal Fatty Acid Synthase. Each of the identical chains in the dimer contains three domains. Domain 1 (blue) contains acetyl transferase (AT), malonyl transferase (MT), and condensing enzyme (CE). Domain 2 (yellow) contains acyl carrier protein (ACP), P-ketoacyl reductase (KR), dehydratase (DH), and enoyl reductase (ER). Domain 3 (red) contains thioesterase (TE). The flexible phosphopantetheinyl group (green) carries the fatty acyl chain from one catalytic site on a chain to another, as well as between chains in the dimer. [After Y. Tsukamoto, H. Wong, J. S. Mattick, and S. J. Wakil. J. Biol. Chem. 258(1983) 15312.]...
KS = /3-Ketoacyl synthase MT = malonyl transacylase AT = acetyl transacylase DH = dehydratase ER = enoyl reductase KR = /3-ketoacyl reductase ACP = acyl carrier site TE = thioesterase. [Reproduced with permission from S. J. Wakil, J. K. Stoops, and V. C. Joshi, Fatty acid synthesis and its regulation. Annu. Rev. Biochem. 52, 537 (1983). 1983 by Annual Reviews Inc.]... [Pg.383]

ACP = acyl carrier protein KS = p-ketoacyl synthase KR = p-ketoacyl reductase ER = enoyl reductase DH = dehydratase TE = thioesterase... [Pg.60]

The answer is e. (Murray, pp 230-267. Scriver, pp 2297-2326. Sack, pp 121-138. Wilson, pp 287-320.) The fatty acid synthase complex of mammals is composed of two identical subunits. Each of the subunits is a multienzyme complex of seven enzymes and the acyl carrier protein component. All the components are covalently linked together thus, all the components are on a single polypeptide chain, which functions in the presence of another identical polypeptide chain. Each cycle of fatty acid synthesis employs the acyl carrier protein and six enzymes acetyl transferase, malonyl transferase, p-ketoacyl synthase, p-ketoacyl reductase, dehydratase, and enoyl reductase. When the final fatty acid length is reached (usually C16), thioesterase hydrolyzes the fatty acid off of the synthase complex. [Pg.226]

Abbreviations FASN, fatty acid synthase ACC, acetyl-CoA-carboxylase ACL, ATP-citrate lyase NADPH, nicotinamide adenine dinucleotide phosphate MAT, malonyl acetyl transferases KS, ketoacyl synthase KR, p-ketoacyl reductase DH, p-hydroxyacyl dehydratase ER, enoyl reductase TE, thioesterase ACP, acyl carrier protein VLCFA, very long chain fatty acids ELOVL, elongation of very long chain fatty acids SCDl, stearoyl-CoA desaturase-1 AMPK, AMP-activated kinase ME, malic enzyme FASKOL, liver-specific deletion of FAS PPARa, Peroxisome Proliferator-Activating Receptor alpha HMG-CoA, 3-hydroxy-3-methyl-glutaryl-CoA SREBP, sterol response element binding protein SIP, site-one protease S2P, site-two... [Pg.169]

Fig. 7.1 The FASN Enzyme. A. The FASN polypeptide comprises seven functional domains the ketoacyl synthase (KS), malonyl acetyl transferase (MAT), P-hydroxyacyl dehydratase (DH), enoyl reductase (ER), P-ketoacyl reductase (KR), the acyl carrier protein (ACP), and thioesterase (TE) domains. B. The FASN reaction mechanism. The MAT domain of the enzyme binds malonyl-CoA and acetyl-CoA, while the KS domain acts to condense the growing acyl chain. The resulting P-ketoacyl moiety is then reduced in steps by the KR, DH, and ER to a saturated acyl intermediate. This process is repeated in seven cycles, after which, the TE domain releases the sixteen carbon fatty acid palmitate... Fig. 7.1 The FASN Enzyme. A. The FASN polypeptide comprises seven functional domains the ketoacyl synthase (KS), malonyl acetyl transferase (MAT), P-hydroxyacyl dehydratase (DH), enoyl reductase (ER), P-ketoacyl reductase (KR), the acyl carrier protein (ACP), and thioesterase (TE) domains. B. The FASN reaction mechanism. The MAT domain of the enzyme binds malonyl-CoA and acetyl-CoA, while the KS domain acts to condense the growing acyl chain. The resulting P-ketoacyl moiety is then reduced in steps by the KR, DH, and ER to a saturated acyl intermediate. This process is repeated in seven cycles, after which, the TE domain releases the sixteen carbon fatty acid palmitate...
Fig. 3. Generic reaction sequence for the FASs. ACP, acyl carrier protein AT, acetyltransferase MT, malonyl transferase KS, P-ketoacyl synthase KR, P-ketoacyl reductase DH, dehydrase ER, enoyl reductase TE, thioesterase FT, palmitoyl transferase. In the animal FAS the acetyl and malonyl loading reactions are catalyzed by the same acyl transferase and the chain-termination reaction is catalyzed by a thioesterase. In the fungal FAS, the malonyl loading and palmitoyl unloading reactions are catalyzed by the same acyl transferase. Stereochemical analyses in the laboratories of Comforth and Hammes established that in both animal and fungal FASs the KS-catalyzed condensation reaction proceeds with inversion of configuration at the malonyl C2 position, followed by KR-catalyzed reduction of the 3-keto moiety to the 3R alcohol by transfer of the pro-4S hydride from NADPH, and DH-catalyzed dehydration to a trans-enoyl moiety by the syn elimination of the 2S hydrogen and the 3/f hydroxyl as water. However, the stereochemistry of the final reduction reaction catalyzed by ER domain proceeds with different stereochemistry. The animal FAS transfers the pro-4R hydride of NADPH to the pro-3/f position with simultaneous addition of a solvent proton to the pro-2S position, whereas the fungal FAS takes the pro-4S hydride of NADPH into the pro-3S position and the solvent proton is incorporated at the pro-25 position. Fig. 3. Generic reaction sequence for the FASs. ACP, acyl carrier protein AT, acetyltransferase MT, malonyl transferase KS, P-ketoacyl synthase KR, P-ketoacyl reductase DH, dehydrase ER, enoyl reductase TE, thioesterase FT, palmitoyl transferase. In the animal FAS the acetyl and malonyl loading reactions are catalyzed by the same acyl transferase and the chain-termination reaction is catalyzed by a thioesterase. In the fungal FAS, the malonyl loading and palmitoyl unloading reactions are catalyzed by the same acyl transferase. Stereochemical analyses in the laboratories of Comforth and Hammes established that in both animal and fungal FASs the KS-catalyzed condensation reaction proceeds with inversion of configuration at the malonyl C2 position, followed by KR-catalyzed reduction of the 3-keto moiety to the 3R alcohol by transfer of the pro-4S hydride from NADPH, and DH-catalyzed dehydration to a trans-enoyl moiety by the syn elimination of the 2S hydrogen and the 3/f hydroxyl as water. However, the stereochemistry of the final reduction reaction catalyzed by ER domain proceeds with different stereochemistry. The animal FAS transfers the pro-4R hydride of NADPH to the pro-3/f position with simultaneous addition of a solvent proton to the pro-2S position, whereas the fungal FAS takes the pro-4S hydride of NADPH into the pro-3S position and the solvent proton is incorporated at the pro-25 position.
Fig. 4. Domain maps of the fungal and animal FAS. Catalytic domains are shown as gray boxes, structural elements in white, the location of the P-chain structural domain I (sdl) is identified in Fig. 5B and D. The region tentatively assigned to the second DH pseudosubunit and the structural domain of the KR has been referred to as the central core. MPT, malonyl/palmitoyltransferase PPT, phosphopantetheinyl transferase MAT, malonyl/acetyltransferase KRs and KRc are structural and catalytic subdomains of the P-ketoacyl reductase other abreviations as in Fig. 2. The yeast alpha-subunit contains 1887 residues and the p subunit, 1845. The animal FAS polypeptide contains -2500 residues. Fig. 4. Domain maps of the fungal and animal FAS. Catalytic domains are shown as gray boxes, structural elements in white, the location of the P-chain structural domain I (sdl) is identified in Fig. 5B and D. The region tentatively assigned to the second DH pseudosubunit and the structural domain of the KR has been referred to as the central core. MPT, malonyl/palmitoyltransferase PPT, phosphopantetheinyl transferase MAT, malonyl/acetyltransferase KRs and KRc are structural and catalytic subdomains of the P-ketoacyl reductase other abreviations as in Fig. 2. The yeast alpha-subunit contains 1887 residues and the p subunit, 1845. The animal FAS polypeptide contains -2500 residues.
Complex lacks a dehydratase domain and two modules lack the ketoacyl reductase domain... [Pg.2427]

Ren Q, Sierro N, Witholt B, Kessler B (2000) FabG, an NADPH-dependent 3-ketoacyl reductase of Pseudomonas aeruginosa, provides precursors for medium-chain-length poly-3-hydroxyal-kanoate biosynthesis in Escherichia coli. J Bacteriol 182 2978—2981 Repaske R, Mayer R (1976) Dense autotrophic culture of Alcaligenes eutrophus. Appl Environ... [Pg.83]

AT = acyl transferase ACP = acyl carrier protein KS = ketosynthase TE = thioesterase KR = (i-ketoacyl reductase ERY = erythromycin RAP = rapamycin... [Pg.69]


See other pages where 3-ketoacyl reductase is mentioned: [Pg.811]    [Pg.123]    [Pg.1187]    [Pg.37]    [Pg.115]    [Pg.71]    [Pg.59]    [Pg.377]    [Pg.327]    [Pg.422]    [Pg.97]    [Pg.105]    [Pg.1514]    [Pg.921]    [Pg.61]    [Pg.638]    [Pg.85]    [Pg.61]    [Pg.236]    [Pg.170]    [Pg.188]    [Pg.274]    [Pg.61]    [Pg.253]    [Pg.49]    [Pg.487]   
See also in sourсe #XX -- [ Pg.377 ]

See also in sourсe #XX -- [ Pg.228 ]




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3-Ketoacyl-ACP reductase

3-Ketoacyl-acyl carrier protein reductase

B-Ketoacyl-ACP-Reductase

Ketoacyl

Ketoacyl-CoA reductase

P-ketoacyl-ACP-reductase

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