Acyl-(acyl-carrier-protein) desaturase

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acyl-[acyl-carrier-protein] desaturase
2XZ0-image1.png
Partially occupied Stearoyl Acyl Carrier Protein Desaturase from Ricinius Communis
Identifiers
EC no. 1.14.19.2
CAS no. 37256-86-3
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In enzymology, an acyl-[acyl-carrier-protein] desaturase (EC 1.14.19.2) is an enzyme that catalyzes the chemical reaction

Contents

stearoyl-[acyl-carrier-protein] + reduced acceptor + O2 oleoyl-[acyl-carrier-protein] + acceptor + 2 H2O

The systematic name of this enzyme class is acyl-[acyl-carrier-protein], hydrogen-donor:oxygen oxidoreductase. Other names in common use include stearyl acyl carrier protein desaturase, and stearyl-ACP desaturase. This enzyme participates in polyunsaturated fatty acid biosynthesis. It employs one cofactor, ferredoxin. [1]

Reaction

The 3 substrates of this enzyme are stearoyl-(acyl-carrier-protein), reduced acceptor, and O2, whereas its 3 products are oleoyl-(acyl-carrier-protein), acceptor, and H2O. [2]

The precise mechanism of this class of enzymes is not known, however recent studies using the kinetic isotope effect suggest that the rate limiting step is the removal of a hydrogen from the carbon nearest the carboxylic acid group. The diiron cluster moves through to a peroxo intermediate which can then dehydrate the short-lived alcohol intermediate, liberating water. [3] There are a variety of specific enzymes within this class that attack using this mechanism, but do so at different points along the carbon chain of their respective fatty acids [3]

Biological Function

This enzyme belongs to the family of oxidoreductases, specifically those acting on paired donors, with O2 as oxidant and incorporation or reduction of oxygen. The oxygen incorporated need not be derived from O2 with oxidation of a pair of donors resulting in the formation of H2O.

This family of enzymes is found only in the plastids of higher plant cells, unlike other desaturases such as acyl-lipid desaturases and acyl-CoA desaturases. [4] The regiospecific role of stearoyl-ACP desaturase is to initialise multiple desaturations by acyl-lipid desaturases. Oleic acid is formed from this reaction is transported to either the thylakoid or cytoplasm to complete desaturation. [5]

Structural studies

As of late 2007, 5 structures have been solved for this class of enzymes, with PDB accession codes 1OQ4, 1OQ7, 1OQ9, 1OQB, and 1ZA0.

Fully bound Stearoyl-acyl-carrier-protein desaturase PDB 2XZ1. 2xz1-image1.png
Fully bound Stearoyl-acyl-carrier-protein desaturase PDB 2XZ1.

2XZ0 and 2XZ1 show the dramatic change in conformation of the enzyme when bound (2XZ1) and unbound (2XZ0). As a dimer, the fatty acid chain binds to a hydrophobic pocket at the interface of the two dimers,. [6] This central channel is mirrored by binding sites for the electron donors on either side.

The stabilisation of the diiron-oxo element required to catalyse the reaction has been of particular interest. Crystallographic studies [7] suggest that the iron groups are held in place by the desaturase using aspartate and glutamate. A structure of aspartate-X-X-histidine was found to be a common motif in several plant species. [8] This desaturase family can be further divided by the consensus motif used to hold the iron clusters in place. Of particular note are the "soluble" desaturases, which use carboxylic acid groups, whereas it is possible for some variants to use histidines instead. The histidine rich desaturases tend to be integral membrane proteins. [6]

Structural studies strongly suggest that the animal form of this enzyme (Stearoyl-acyl-carrier-protein desaturase) is evolutionarily divergent from the forms found in plants and fungi. [9] This is to be expected as the roles of the enzymes are different in both. For example, in insects, the desaturase is critical in the formation of ceramide, and for complex signalling molecules (pheremones), [3] while in fungi, the function of the enzyme, and concentration of unsaturated lipids is regulated in response to function of growth temperature by controlling membrane fluidity in cells. [10]

Potential Industrial Relevance

This enzyme class plays a critical role in the biosynthesis of unsaturated fatty acids in plants, and are very specific to their substrates. [3] A common theme in recent research has been to identify uncommon desaturases in various plants [6] [11] and isolate their genetic code. In particular, this can then be inserted into model cells (such as Escherichia coli) and up-regulated through metabolic engineering to skew the composition of oils produced by the model cells. [12]

This becomes a particularly lucrative endeavour if it becomes possible to successfully synthesise so-called Omega-3 fatty acids or other nutraceutical products from basic saturated fatty acids, and extract them from their hosts.

Related Research Articles

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Coenzyme A (CoA, SHCoA, CoASH) is a coenzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle. All genomes sequenced to date encode enzymes that use coenzyme A as a substrate, and around 4% of cellular enzymes use it (or a thioester) as a substrate. In humans, CoA biosynthesis requires cysteine, pantothenate (vitamin B5), and adenosine triphosphate (ATP).

Fatty acid desaturases are a family of enzymes that convert saturated fatty acids into unsaturated fatty acids and polyunsaturated fatty acids. For the common fatty acids of the C18 variety, desaturases convert stearic acid into oleic acid. Other desaturases convert oleic acid into linolenic acid, which is the precursor to alpha-linolenic acid, gamma-linolenic acid, and eicosatrienoic acid.

Cytochrome b<sub>5</sub>

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<span class="mw-page-title-main">Cyclopropane fatty acid</span>

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<span class="mw-page-title-main">Beta-ketoacyl-ACP synthase</span> Enzyme

In molecular biology, Beta-ketoacyl-ACP synthase EC 2.3.1.41, is an enzyme involved in fatty acid synthesis. It typically uses malonyl-CoA as a carbon source to elongate ACP-bound acyl species, resulting in the formation of ACP-bound β-ketoacyl species such as acetoacetyl-ACP.

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<span class="mw-page-title-main">Stearoyl-CoA 9-desaturase</span> Class of enzymes

Stearoyl-CoA desaturase (Δ-9-desaturase) is an endoplasmic reticulum enzyme that catalyzes the rate-limiting step in the formation of monounsaturated fatty acids (MUFAs), specifically oleate and palmitoleate from stearoyl-CoA and palmitoyl-CoA. Oleate and palmitoleate are major components of membrane phospholipids, cholesterol esters and alkyl-diacylglycerol. In humans, the enzyme is encoded by the SCD gene.

<span class="mw-page-title-main">FADS2</span>

Fatty acid desaturase 2 (FADS2) is encoded by the FADS2 gene, the associated enzyme is sometimes known as FADS2 as well. Its main associated enzyme is Delta 6 desaturase (D6D) however the human enzyme was shown to also catalyze some delta-8 and delta-4 desaturation reactions despite naming conventions.

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<span class="mw-page-title-main">FADS1</span> Protein-coding gene in the species Homo sapiens

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Delta12-fatty-acid desaturase (EC 1.14.19.6, Delta12 fatty acid desaturase, Delta12(omega6)-desaturase, oleoyl-CoA Delta12 desaturase, Delta12 desaturase, Delta12-desaturase) is an enzyme with systematic name acyl-CoA,hydrogen donor:oxygen Delta12-oxidoreductase. This enzyme catalyses the following chemical reaction

3-hydroxydecanoyl-(acyl-carrier-protein) dehydratase (EC 4.2.1.60, D-3-hydroxydecanoyl-[acyl-carrier protein] dehydratase, 3-hydroxydecanoyl-acyl carrier protein dehydrase, 3-hydroxydecanoyl-acyl carrier protein dehydratase, β-hydroxydecanoyl thioester dehydrase, β-hydroxydecanoate dehydrase, beta-hydroxydecanoyl thiol ester dehydrase, FabA, β-hydroxyacyl-acyl carrier protein dehydratase, HDDase, β-hydroxyacyl-ACP dehydrase, (3R)-3-hydroxydecanoyl-[acyl-carrier-protein] hydro-lyase) is an enzyme with systematic name (3R)-3-hydroxydecanoyl-(acyl-carrier protein) hydro-lyase. This enzyme catalyses the following chemical reaction

Stearoyl-CoA is a coenzyme involved in the metabolism of fatty acids. Stearoyl-CoA is an 18-carbon long fatty acyl-CoA chain that participates in an unsaturation reaction. The reaction is catalyzed by the enzyme stearoyl-CoA desaturase, which is located in the endoplasmic reticulum. It forms a cis-double bond between the ninth and tenth carbons within the chain to form the product oleoyl-CoA.

<span class="mw-page-title-main">Ketoacyl synthase</span> Catalyst for a key step in fatty acid synthesis

Ketoacyl synthases (KSs) catalyze the condensation reaction of acyl-CoA or acyl-acyl ACP with malonyl-CoA to form 3-ketoacyl-CoA or with malonyl-ACP to form 3-ketoacyl-ACP. This reaction is a key step in the fatty acid synthesis cycle, as the resulting acyl chain is two carbon atoms longer than before. KSs exist as individual enzymes, as they do in type II fatty acid synthesis and type II polyketide synthesis, or as domains in large multidomain enzymes, such as type I fatty acid synthases (FASs) and polyketide synthases (PKSs). KSs are divided into five families: KS1, KS2, KS3, KS4, and KS5.

References

  1. ↑ Jacobson, BS; Jaworski J; Stumpf PF (1974). "Fat Metabolism in Higher Plants LXII. Stearl-acyl Carrier Protein Desaturase from Spinach Chloroplasts". Plant Physiology. 54 (4): 484–486. doi:10.1104/pp.54.4.484. ISSN   0032-0889. PMC   367438 . PMID   16658913.
  2. ↑ Nagai J, Bloch K (1968). "Enzymatic desaturation of stearyl acyl carrier protein". J. Biol. Chem. 243 (17): 4626–33. doi: 10.1016/S0021-9258(18)93235-7 . PMID   4300868.
  3. 1 2 3 4 Behrouzian, B; Buist, BH (2002). "Fatty acid desaturation: variations on an oxidative theme". Current Opinion in Chemical Biology. 6 (5): 577–82. doi:10.1016/S1367-5931(02)00365-4. PMID   12413540.
  4. ↑ Murphy, D (1999). "Production of novel oils in plants". Current Opinion in Biotechnology. 10 (2): 175–180. doi:10.1016/S0958-1669(99)80031-7. PMID   10209131.
  5. ↑ Los, D; Murata,N (1998). "Structure and expression of fatty acid desaturases". Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism. 1394 (1): 3–15. doi:10.1016/S0005-2760(98)00091-5. PMID   9767077.
  6. 1 2 3 Shanklin, J; Cahoon, E (1998). "Desaturation and related modifications of fatty acids". Annual Review of Plant Physiology and Plant Molecular Biology. 49: 611–641. doi:10.1146/annurev.arplant.49.1.611. PMID   15012248.
  7. ↑ Fox, BG; Sommerville,C.; Munck, E (15 March 1993). "Stearoyl-acyl carrier protein delta 9 desaturase from Ricinus communis is a diiron-oxo protein". Proceedings of the National Academy of Sciences. 90 (6): 2486–2490. doi: 10.1073/pnas.90.6.2486 . PMC   46112 . PMID   8460163.
  8. ↑ Haralampidis, K; D. Milioni; J. Sanchez; M. Baltrusch; E. Heinz; P. Hatzopoulos (1998). "Temporal and transient expression of stearoyl-ACP carrier protein desaturase gene during olive fruit development". Journal of Experimental Botany. 49 (327): 1661–1669. doi: 10.1093/jxb/49.327.1661 .
  9. ↑ Shanklin J, Somerville C (1991). "Stearoyl-acyl-carrier-protein desaturase from higher plants is structurally unrelated to the animal and fungal homologs". Proc. Natl. Acad. Sci. U.S.A. 88 (6): 2510–2514. Bibcode:1991PNAS...88.2510S. doi: 10.1073/pnas.88.6.2510 . PMC   51262 . PMID   2006187.
  10. ↑ Magnuson, K; Jackowski, S.; Rock, C.; Cronan, J. (1993). "Regulation of fatty acid biosynthesis in Escherichia coli". Microbiological Reviews. 57 (3): 522–542. doi:10.1128/MMBR.57.3.522-542.1993. PMC   372925 . PMID   8246839.
  11. ↑ Schultz, D; Suh, M.; Ohlrogge (2000). "Stearoyl-Acyl Carrier Protein and Unusual Acyl-Acyl Carrier Protein Desaturase Activities Are Differentially Influenced by Ferredoxin". Plant Physiology. 124 (2): 681–692. doi:10.1104/pp.124.2.681. PMC   59173 . PMID   11027717.
  12. ↑ Cahoon, E; Mills, L.; Shanklin, J. (1996). "Modification of the fatty acid composition of Escherichia coli by coexpression of a plant acyl-acyl carrier protein desaturase and ferredoxin". Journal of Bacteriology. 178 (3): 936–939. doi:10.1128/jb.178.3.936-939.1996. PMC   177750 . PMID   8550538.
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