If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
|Superclasses:||Biosynthesis → Fatty Acid and Lipid Biosynthesis → Fatty Acid Biosynthesis → Hydroxylated Fatty Acids Biosynthesis|
Expected Taxonomic Range: Viridiplantae
Plants contain significant amounts of hydroxy fatty acids in their sphingolipids. Hydroxy fatty acids are used extensively by several industries. The importance of hydroxylated fatty acids for commercial and nutritional purposes resulted in efforts to develop metabolic engineered pathways for these compounds [Somerville96, Thelen02].
Most of the enzymes involved in the formation of hydroxylated fatty acids have been characterized from species of the Brassicaceae family, which contains a high percentage of hydroxylated fatty acids in their seed oil. Biosynthesis of hydroxylated fatty acids takes place at the endoplasmatic reticulum, and includes the microsomal fatty acid elongation (FAE) system and desaturase enzymes [Browse91, Moon01]. It should be noted that while the elongase system accepts only coenzyme-A esters [Fehling91], other enzymes such as desaturases and hydroxylases act on fatty acids esterified to a glycerolipid backbone (usually to the sn-2 position of the membrane lipid phosphatidylcholin) [Bafor91, Lin96]. This requires the reversible transfer of fatty acids between lipids and coA-esters, which is essential part of the pathway.
It should also be noted that although acyl-CoA hydrolases exist to release fatty acids from coenzyme A, free fatty acids are considered toxic and therefore are very rare inside the cell (Ed Cahoon 2013, personal communication).
About This Pathway
The seeds of Arabidopsis [Smith00] and Ricinus
The pathway in Physaria shown here, which is based on labeling studies [Reed97], starts with formation of ricinoleate by an oleate 12-hydroxylase [Broun98, Dauk07], followed by desaturation to densipolate [Broun98, Engeseth96].
The further steps towards the biosynthesis of lesquerolate may occur either through the elongation of ricinoleate or the hydroxylation of gondoate [Lin96, Broun97]. The elongation of oleoyl-CoA to form (11Z)-icosenoyl-CoA has been demonstrated in various species [Fehling91, Moon01, Ghanevati01]. The final reactions leading to auricolate remain to be demonstrated.
Bafor91: Bafor M, Smith MA, Jonsson L, Stobart K, Stymne S (1991). "Ricinoleic acid biosynthesis and triacylglycerol assembly in microsomal preparations from developing castor-bean (Ricinus communis) endosperm." Biochem J 280 ( Pt 2);507-14. PMID: 1747126
Broun97: Broun P, Somerville C (1997). "Accumulation of ricinoleic, lesquerolic, and densipolic acids in seeds of transgenic Arabidopsis plants that express a fatty acyl hydroxylase cDNA from castor bean." Plant Physiol 113(3);933-42. PMID: 9085577
Dierig04: Dierig DA, Tomasi PM, Salywon AM, Ray DT (2004). "Improvement in hydroxy fatty acid seed oil content and other traits from interspecific hybrids of three Lesquerella species: Lesquerella fendleri, L. pallida, and L. lindheimeri." Euphytica 139:199-206.
Fehling91: Fehling E, Mukherjee KD (1991). "Acyl-CoA elongase from a higher plant (Lunaria annua): metabolic intermediates of very-long-chain acyl-CoA products and substrate specificity." Biochim Biophys Acta 1082(3);239-46. PMID: 2029543
Ghanevati01: Ghanevati M, Jaworski JG (2001). "Active-site residues of a plant membrane-bound fatty acid elongase beta-ketoacyl-CoA synthase, FAE1 KCS." Biochim Biophys Acta 2001;1530(1);77-85. PMID: 11341960
Hayes95: Hayes DG, Kleiman R, Philipps BS (1995). "The triglyceride composition, structure, and presence of estolides in the oils of Lesquerella and related species." J. Am. Oil Chem. Soc. 5: 559-569.
Lin96: Lin JT, McKeon TA, Goodrich-Tanrikulu M, Stafford AE (1996). "Characterization of oleoyl-12-hydroxylase in castor microsomes using the putative substrate, 1-acyl-2-oleoyl-sn-glycero-3-phosphocholine." Lipids 31(6);571-7. PMID: 8784737
Reed97: Reed DW, Taylor DC, Covello PS (1997). "Metabolism of Hydroxy Fatty Acids in Developing Seeds in the Genera Lesquerella (Brassicaceae) and Linum (Linaceae)." Plant Physiol 114(1);63-68. PMID: 12223689
Somerville96: Somerville C, Broun P, Van De Loo FJ (1996). "Production of hydroxylated fatty acids in genetically modified plants." Patent Cooperation Treaty International Appl. No. PCT/ US95 / 11855.
Goldfine71: Goldfine H, Panos C (1971). "Phospholipids of Clostridium butyricum. IV. Analysis of the positional isomers of monounsaturated and cyclopropane fatty acids and alk-1'-enyl ethers by capillary column chromatography." J Lipid Res 12(2);214-20. PMID: 5554109
Jaworski74: Jaworski JG, Stumpf PK (1974). "Fat metabolism in higher plants. Properties of a soluble stearyl-acyl carrier protein desaturase from maturing Carthamus tinctorius." Arch Biochem Biophys 162(1);158-65. PMID: 4831331
Kumar06: Kumar R, Wallis JG, Skidmore C, Browse J (2006). "A mutation in Arabidopsis cytochrome b5 reductase identified by high-throughput screening differentially affects hydroxylation and desaturation." Plant J 48(6);920-32. PMID: 17227547
Lager13: Lager I, Yilmaz JL, Zhou XR, Jasieniecka K, Kazachkov M, Wang P, Zou J, Weselake R, Smith MA, Bayon S, Dyer JM, Shockey JM, Heinz E, Green A, Banas A, Stymne S (2013). "Plant acyl-CoA:lysophosphatidylcholine acyltransferases (LPCATs) have different specificities in their forward and reverse reactions." J Biol Chem 288(52);36902-14. PMID: 24189065
Napier03: Napier JA, Michaelson LV, Sayanova O (2003). "The role of cytochrome b5 fusion desaturases in the synthesis of polyunsaturated fatty acids." Prostaglandins Leukot Essent Fatty Acids 68(2);135-43. PMID: 12538077
Rubio06: Rubio S, Larson TR, Gonzalez-Guzman M, Alejandro S, Graham IA, Serrano R, Rodriguez PL (2006). "An Arabidopsis mutant impaired in coenzyme A biosynthesis is sugar dependent for seedling establishment." Plant Physiol 140(3);830-43. PMID: 16415216
Smith62: Smith C R, Wilson T L, Bates R B, Scholfield C R (1962). "Densipolic Acid: a Unique Hydroxydienoid Acid from Lesquerella densipila Seed Oil." The Journal of Organic Chemistry 27(9);3112-3117.
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