Shanklin, John - Stony Brook University

研究领域

Lipids are a major functional components of all living things. Despite their importance, the details of lipid synthesis and modification are incomplete. Lipids are first synthesized as saturated fatty acids and double bonds are incorporated post-synthetically by enzymes known as fatty acid desaturases; in a process that is initiated by cleavage of the stable methylene C-H bond. This reaction involves high energy chemistry, the details of which we are trying to elucidate. We are also interested in using this class of enzymes to further our understanding the basis for enzyme specificity and selectivity. Much of the tremendous diversity of fatty acids found in nature is due to the presence of variant desaturase-like enzymes. Desaturation of a fatty acid results in dramatic effects on the physical properties of both cell membranes and storage lipids, and the placement of double bonds, triple bonds, hydroxy groups, epoxy groups, and various conjugated double bond systems determines the uses to which these fatty acids can be put.

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Wang W., Haberer G., Gundlach H., Gläβer C., Nussbaumer T., Luo M.C., Lomsadze A., Borodovsky M., Kerstetter R.A., Shanklin J., Bryant D.W., Mockler T.C., Appenroth K.J., Grimwood J., Jenkins J., Chow J., Choi C., Adam C., Cao X.-H., Fuchs J., Schubert I., Rokhsar D., Schmutz J., Michael T.P., Mayer K.F.X., and Messing J. The Spirodela polyrhiza genome reveals insights into its neotenous reduction fast growth and aquatic lifestyle. Nature Communications (Epub February 19, 2014). Yu, X.-H., Prakash, R. R., Sweet, M., and Shanklin, J. Coexpressing Escherichia coli cyclopropane synthase with Sterculia foetida lysophosphatidic acid acyltransferase enhances cyclopropane fatty acid accumulation. Plant Physiol., 164(1):455-465 (2014). Yan Y., Candreva J., Shi H., Ernst E., Martienssen R., Schwender J., and Shanklin J. Survey of the total fatty acid and triacylglycerol composition and content of 30 duckweed species and cloning of a Δ6-desaturase responsible for the production of γ-linolenic and stearidonic acids in Lemna gibba. BMC Plant Biology, 13:201 (2013). Andre C., Kim S.-W., Yu X.-H., and Shanklin J. Fusing catalase to an alkane-producing enzyme maintains enzymatic activity by converting the inhibitory byproduct H2O2 to the cosubstrate O2. Proc. Natl. Acad. Sci. USA 110(8):3191-3196 (2013). Cooper H.L.R., Mishra G., Huang X., Pender-Cudlip M., Austin R.N., Shanklin J., Groves J.T. Parallel and competitive pathways for substrate desaturation, hydroxylation, and radical rearrangement by the non-heme diiron hydroxylase AlkB. J. Am. Chem. Soc., 134(50):20365-20375 (2012). Andre C., Haslam R., and Shanklin J. Feedback regulation of plastidic Acetyl-CoA carboxylase by 18:1-acyl carrier protein in Brassica napus. Proc. Natl. Acad. Sci. USA, 109(25):10107-10112 (2012). Fan J., Yan C., Andre C., Shanklin J., Schwender J., and Xu C. Oil accumulation is controlled by carbon precursor supply for fatty acid synthesis in Chlamydomonas reinhardtii. Plant Cell Physiol., 53(8): 1380-1390 (2012). Rawat R., Yu X.H., Sweet M., and Shanklin J. Conjugated fatty acid synthesis: residues 111 and 115 influence product partitioning of the Momordica charantia conjugase. J. Biol. Chem., 287(20):16230-16237 (2012). PubMed Chen W., Yu X.-H., Zhang K., Shi J., Schreiber L., Shanklin J., and Zhang D. Male Sterile2 encodes a plastid-localized fatty acyl carrier protein reductase required for pollen exine development in Arabidopsis. Plant Physiol., 157(2):842-853 (2011). PubMed Guy J.E., Whittle E., Moche M., Lengqvist J., Lindqvist Y., and Shanklin J. Remote control of regioselectivity in acyl-acyl carrier protein-desaturases. Proc. Natl. Acad. Sci. USA, 108(40):16594-16599 (2011). PubMed Schluter P.M., Xu S., Gagliardini V. Whittle, E., Shanklin J., Grossniklaus U., and Schiestl F.P. Stearoyl-acyl carrier protein desaturases are associated with floral isolation in sexually deceptive orchids. Proc. Natl. Acad. Sci. USA, 108(14):5696-5701 (2011). PubMed Shi J., Tan H., Yu X.-H., Liu Y., Liang W., Ranathunge K., Franke R.B., Schreiber L., Wang Y., Kai G., Shanklin J., Ma H., and Zhang D. Defective Pollen Wall is required for anther and microspore development in rice and encodes a fatty acyl carrier protein reductase. Plant Cell, 23(6):2225-2246 (2011). PubMed Yu X.-H., Rawat R., and Shanklin J. Characterization and analysis of the cotton cyclopropane fatty acid synthase family and their contribution to cyclopropane fatty acid synthesis. BMC Plant Biology, 11:97 (2011). PubMed Lou Y. and Shanklin J. Evidence that the yeast desaturase Ole1p exists as a dimer in vivo. J. Biol. Chem., 285(25):19384-19390 (2010). Nguyen H.T., Mishra G., Whittle E., Bevan S.A., Merlo A.O., Walsh T.A., and Shanklin J. Metabolic engineering of seeds can achieve levels of ω-7 fatty acids comparable to the highest levels found in natural plant sources. Plant Physiol., 154(4):1897-1904 (2010). Tremblay A.E., Tan N., Whittle E., Hodgson D.J., Dawson B., Buist P.H., and Shanklin J. Stereochemistry of 10-sulfoxidation catalyzed by a soluble Δ9 desaturase. Organic & Biomolecular Chemistry, 8(6):1322-1328 (2010). Nguyen H.T. and Shanklin J. Altering Arabidopsis oilseed composition by a combined antisense-hairpin RNAi gene suppressing approach. J. Amer. Oil Chemists Soc., 86(1):41-49 (2009). Shanklin J., Guy J.E., Mishra G., and Lindqvist Y. Desaturases: Emerging models for understanding functional diversification of diiron-containing enzymes. Journal of Biological Chemistry 284(28): 18559-18563 (July, 2009). Shanklin J. Enzyme engineering. Advances in Plant Biochemistry and Molecular Biology, Vol. 1: Bioengineering and Molecular Biology of Plant Pathways, H. J. Bohnert, H. Nguyen, and N. Lewis, Editors, Chapter 2, Elsevier Science Ltd., Oxford, U.K. (2008). Whittle E.J., Tremblay A.E., Buist P.H. and Shanklin J. Revealing the catalytic potential of an acyl-ACP desaturase: Tandem selective oxidation of saturated fatty acids. Proceedings of the National Academy of Sciences, 105(38):14738-14743 (2008). Zhang P., Burton J.W., Upchurch R.G., Whittle E., Shanklin J. and Dewey R.E. Mutations in a Δ9-stearoyl-ACP-desaturase gene are associated with enhanced stearic acid levels in soybean seeds. Crop Science, 48:2305-2313 (November-December, 2008). Guy J.E., Whittle E., Kumaran D., Lindqvist Y. and Shanklin J. The crystal structure of the ivy Δ4-16:0-ACP desaturase reveals structural details of the oxidized active site and potential determinants of regioselectivity. J. Biol. Chem., 282(27):19863-19871 (2007). Kachroo A., Shanklin J., Whittle E., Lapchyk L., Hildebrand D. and Kachroo P. The Arabidopsis stearoyl-acyl carrier protein-desaturase family and the contribution of leaf isoforms to oleic acid synthesis. Plant Molec. Biol., 63(2):257-271 (2007). Mayer K.M. and Shanklin J. Identification of amino acid residues involved in substrate specificity of plant acyl-ACP thioesterases using bioinformatics-guided approach. BMC Plant Biol., 7:1 (2007). Pidkowich M.S., Nguyen H.T., Heilmann I., Ischebeck T. and Shanklin J. Modulating seed β-ketoacyl-acyl carrier protein synthase II level converts the composition of a temperate seed oil to that of a palm-like tropical oil. Proc. Natl. Acad. Sci. USA, 104(11):4742-4747 (2007). Shanklin J. and Whittle E. Acyl-ACP desaturase architecture favors high-energy desaturation reaction over lower-energy oxidase chemistry. Current Advances in the Biochemistry and Cell Biology of Plant Lipids, Proceedings of the 17th International Symposium on Plant Lipids, July 16-21, 2006, Michigan State University, East Lansing, MI, C. Benning and J. Ohlrogge, Editors, pp. 207-209, Aardvark Global Publishing Company, LLC, Salt Lake City, UT. (2007). Tremblay A.E., Whittle E., Buist P.H. and Shanklin J. Stereochemistry of Δ4 dehydrogenation catalyzed by a Δ9 desaturase homolog. Organic Biomolec. Chem., 5(8):1270-1275 (2007). Guy J.E., Abreu I.A., Moche M., Lindqvist Y., Whittle E. and Shanklin J. A single mutation in the castor Δ9-18:0-desaturase changes reaction partitioning from Desaturation to oxidase chemistry. Proc. Natl. Acad. Sci. USA, 103(46):17220-17224 (2006). Tremblay A.E., Buist P.H., Hodgson D., Dawson B., Whittle E. and Shanklin J. In vitro enzymatic oxidation of a fluorine-tagged sulfide substrate analogue: A 19F NMR investigation. Magnetic Resonance in Chemistry, 44(6):629-632 (2006). Davydov R., Behrouzian B., Smoukov S., Stubbe J., Hoffman B.M., and Shanklin J. Effect of substrate on the diiron(III) site in stearoyl acyl carrier protein delta(9)-desaturase as disclosed by cryoreduction electron paramagnetic resonance/electron nuclear double resonance spectroscopy. Biochemistry, 44:1309-1315 (2005). Mayer K.M., McCorkle S.R. and Shanklin J. Linking enzyme sequence to function using conserved property difference locator to identify and annotate positions likely to control specific functionality. BMC Bioinformatics, 6:284 (2005). Mayer KM, and Shanklin J. A structural model of the plant acyl-acyl carrier protein thioesterase FatB comprises two helix/4-stranded sheet domains, the N-terminal domain containing residues that affect specificity and the C-terminal domain containing catalytic residues. J. Biol. Chem., 280:3621-3627 (2005). PDB file: 1XXY Whittle E., Cahoon E.B., Subrahmanyam S. and Shanklin J. A multifunctional acyl-acyl carrier protein desaturase from Hedera helix L. (English ivy) can synthesize 16- and 18-carbon monoene and diene products. J. Biol Chem. June 6,(2005). Heilmann I., Mekhedov S., King B., Browse J. and Shanklin J. Identification of the Arabidopsis palmitoyl-monogalactosyldiacylglycerol delta7-desaturase gene FAD5, and effects of plastidial retargeting of Arabidopsis desaturases on the fad5 mutant phenotype. Plant Physiol., 136:4237-4245 (2004). Heilmann I., Pidkowich M.S., Girke T. and Shanklin J. Switching desaturase enzyme specificity by alternate subcellular targeting. Proc Natl Acad Sci USA, 101:10266-10271 (2004). Reipa V., Shanklin J. and Vilker V. Substrate binding and the presence of ferredoxin affect the redox properties of the soluble plant Delta9-18:0-acyl carrier protein desaturase. Chem. Commun. (Camb)., 21:2406-2407 (2004).