MetaCyc Pathway: hydroxylated fatty acid biosynthesis (plants)
Traceable author statement to experimental supportInferred from experiment

Pathway diagram: hydroxylated fatty acid biosynthesis (plants)

If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: BiosynthesisFatty Acid and Lipid BiosynthesisFatty Acid BiosynthesisHydroxylated Fatty Acids Biosynthesis

Some taxa known to possess this pathway include : Physaria fendleri, Physaria kathryn, Physaria lindheimeri

Expected Taxonomic Range: Viridiplantae

General Background

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 [Moreau81] accumulate the hydroxylated fatty acid ricinoleate. The seeds of species of Physaria contain high amounts of lesquerolate as well as the more more desaturated densipolate and auricolate [Hayes95, Dierig04].

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.

Created 15-Feb-2010 by Pujar A, Boyce Thompson Institute
Revised 16-May-2013 by Foerster H, Boyce Thompson Institute
Revised 01-Dec-2014 by Caspi R, SRI International


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

Broun98: Broun P, Boddupalli S, Somerville C (1998). "A bifunctional oleate 12-hydroxylase: desaturase from Lesquerella fendleri." Plant J 13(2);201-10. PMID: 9680976

Browse91: Browse JP, Somerville CR (1991). "Glycerolipid synthesis: biochemistry and regulation." Annu Rev Plant Physiol Mol Biol 42:467-506.

Dauk07: Dauk M, Lam P, Kunst L, Smith MA (2007). "A FAD2 homologue from Lesquerella lindheimeri has predominantly fatty acid hydroxylase activity." Plant Science 173:43-49.

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.

Engeseth96: Engeseth N, Stymne S (1996). "Desaturation of oxygenated fatty acids in Lesquerella and other oil seeds." Planta 198:238-245.

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

Moon01: Moon H, Smith MA, Kunst L (2001). "A condensing enzyme from the seeds of Lesquerella fendleri that specifically elongates hydroxy fatty acids." Plant Physiol 127(4);1635-43. PMID: 11743108

Moreau81: Moreau RA, Stumpf PK (1981). "Recent studies of the enzymic synthesis of ricinoleic Acid by developing castor beans." Plant Physiol 67(4);672-6. PMID: 16661734

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

Smith00: Smith M, Moon H, Kunst L (2000). "Production of hydroxy fatty acids in the seeds of Arabidopsis thaliana." Biochem Soc Trans 28(6);947-50. PMID: 11171267

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.

Thelen02: Thelen JJ, Ohlrogge JB (2002). "Metabolic engineering of fatty acid biosynthesis in plants." Metab Eng 4(1);12-21. PMID: 11800570

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Bi13: Bi H, Wang H, Cronan JE (2013). "FabQ, a dual-function dehydratase/isomerase, circumvents the last step of the classical fatty acid synthesis cycle." Chem Biol 20(9);1157-67. PMID: 23972938

Biebl02: Biebl H, Sproer C (2002). "Taxonomy of the glycerol fermenting clostridia and description of Clostridium diolis sp. nov." Syst Appl Microbiol 25(4);491-7. PMID: 12583708

Ghanevati02: Ghanevati M, Jaworski JG (2002). "Engineering and mechanistic studies of the Arabidopsis FAE1 beta-ketoacyl-CoA synthase, FAE1 KCS." Eur J Biochem 269(14);3531-9. PMID: 12135493

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

Johnston83: Johnston NC, Goldfine H (1983). "Lipid composition in the classification of the butyric acid-producing clostridia." J Gen Microbiol 129(4);1075-81. PMID: 6886674

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

Kumar12: Kumar R, Tran LS, Neelakandan AK, Nguyen HT (2012). "Higher plant cytochrome b5 polypeptides modulate fatty acid desaturation." PLoS One 7(2);e31370. PMID: 22384013

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

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Lederer94: Lederer F (1994). "The cytochrome b5-fold: an adaptable module." Biochimie 76(7);674-92. PMID: 7893819

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

Scheuerbrandt61: Scheuerbrandt G, Goldfine H, Baronowsky PE, Bloch K (1961). "A novel mechanism for the biosynthesis of unsaturated fatty acids." J Biol Chem 236;PC70-PC71. PMID: 14498314

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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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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