title: The last step in cocaine biosynthesis is catalyzed by a BAHD acyltransferase.
abstract: The esterification of methylecgonine (2-carbomethoxy-3β-tropine) with benzoic acid is the final step in the biosynthetic pathway leading to the production of cocaine in Erythoxylum coca. Here we report the identification of a member of the BAHD family of plant acyltransferases as cocaine synthase. The enzyme is capable of producing both cocaine and cinnamoylcocaine via the activated benzoyl- or cinnamoyl-Coenzyme A thioesters, respectively. Cocaine synthase activity is highest in young developing leaves, especially in the palisade parenchyma and spongy mesophyll. These data correlate well with the tissue distribution pattern of cocaine as visualized with antibodies. Matrix-assisted laser-desorption ionization mass spectral imaging revealed that cocaine and cinnamoylcocaine are differently distributed on the upper versus lower leaf surfaces. Our findings provide further evidence that tropane alkaloid biosynthesis in the Erythroxylaceae occurs in the above-ground portions of the plant in contrast with the Solanaceae, in which tropane alkaloid biosynthesis occurs in the roots.
authors.affiliation: Department of Biochemistry, Max Planck Institute for Chemical Ecology, Beutenberg Campus, D-07745 Jena, Germany (G.W.S., J.J., M.R., K.L., J.C.P.T., F.D., J.G., J.C.D.); andLife Sciences Mass Spectrometry Research Unit, School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 1211 Geneva, Switzerland (T.P., E.V., G.H.).
authors.forename: Gregor Wolfgang
authors.initials: GW
authors.lastname: Schmidt
authors.affiliation: Department of Biochemistry, Max Planck Institute for Chemical Ecology, Beutenberg Campus, D-07745 Jena, Germany (G.W.S., J.J., M.R., K.L., J.C.P.T., F.D., J.G., J.C.D.); andLife Sciences Mass Spectrometry Research Unit, School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 1211 Geneva, Switzerland (T.P., E.V., G.H.).
authors.forename: Jan
authors.identifier: http://orcid.org/0000-0003-1007-4700
authors.initials: J
authors.lastname: Jirschitzka
authors.affiliation: Department of Biochemistry, Max Planck Institute for Chemical Ecology, Beutenberg Campus, D-07745 Jena, Germany (G.W.S., J.J., M.R., K.L., J.C.P.T., F.D., J.G., J.C.D.); andLife Sciences Mass Spectrometry Research Unit, School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 1211 Geneva, Switzerland (T.P., E.V., G.H.).
authors.forename: Tiffany
authors.initials: T
authors.lastname: Porta
authors.affiliation: Department of Biochemistry, Max Planck Institute for Chemical Ecology, Beutenberg Campus, D-07745 Jena, Germany (G.W.S., J.J., M.R., K.L., J.C.P.T., F.D., J.G., J.C.D.); andLife Sciences Mass Spectrometry Research Unit, School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 1211 Geneva, Switzerland (T.P., E.V., G.H.).
authors.forename: Michael
authors.initials: M
authors.lastname: Reichelt
authors.affiliation: Department of Biochemistry, Max Planck Institute for Chemical Ecology, Beutenberg Campus, D-07745 Jena, Germany (G.W.S., J.J., M.R., K.L., J.C.P.T., F.D., J.G., J.C.D.); andLife Sciences Mass Spectrometry Research Unit, School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 1211 Geneva, Switzerland (T.P., E.V., G.H.).
authors.forename: Katrin
authors.initials: K
authors.lastname: Luck
authors.affiliation: Department of Biochemistry, Max Planck Institute for Chemical Ecology, Beutenberg Campus, D-07745 Jena, Germany (G.W.S., J.J., M.R., K.L., J.C.P.T., F.D., J.G., J.C.D.); andLife Sciences Mass Spectrometry Research Unit, School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 1211 Geneva, Switzerland (T.P., E.V., G.H.).
authors.forename: José Carlos Pardo
authors.initials: JC
authors.lastname: Torre
authors.affiliation: Department of Biochemistry, Max Planck Institute for Chemical Ecology, Beutenberg Campus, D-07745 Jena, Germany (G.W.S., J.J., M.R., K.L., J.C.P.T., F.D., J.G., J.C.D.); andLife Sciences Mass Spectrometry Research Unit, School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 1211 Geneva, Switzerland (T.P., E.V., G.H.).
authors.forename: Franziska
authors.initials: F
authors.lastname: Dolke
authors.affiliation: Department of Biochemistry, Max Planck Institute for Chemical Ecology, Beutenberg Campus, D-07745 Jena, Germany (G.W.S., J.J., M.R., K.L., J.C.P.T., F.D., J.G., J.C.D.); andLife Sciences Mass Spectrometry Research Unit, School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 1211 Geneva, Switzerland (T.P., E.V., G.H.).
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Varesio
authors.affiliation: Department of Biochemistry, Max Planck Institute for Chemical Ecology, Beutenberg Campus, D-07745 Jena, Germany (G.W.S., J.J., M.R., K.L., J.C.P.T., F.D., J.G., J.C.D.); andLife Sciences Mass Spectrometry Research Unit, School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 1211 Geneva, Switzerland (T.P., E.V., G.H.).
authors.forename: Gérard
authors.initials: G
authors.lastname: Hopfgartner
authors.affiliation: Department of Biochemistry, Max Planck Institute for Chemical Ecology, Beutenberg Campus, D-07745 Jena, Germany (G.W.S., J.J., M.R., K.L., J.C.P.T., F.D., J.G., J.C.D.); andLife Sciences Mass Spectrometry Research Unit, School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 1211 Geneva, Switzerland (T.P., E.V., G.H.).
authors.forename: Jonathan
authors.initials: J
authors.lastname: Gershenzon
authors.affiliation: Department of Biochemistry, Max Planck Institute for Chemical Ecology, Beutenberg Campus, D-07745 Jena, Germany (G.W.S., J.J., M.R., K.L., J.C.P.T., F.D., J.G., J.C.D.); andLife Sciences Mass Spectrometry Research Unit, School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 1211 Geneva, Switzerland (T.P., E.V., G.H.) john.c.dauria@ttu.edu.
authors.forename: John Charles
authors.identifier: http://orcid.org/0000-0002-4865-3938
authors.initials: JC
authors.lastname: D'Auria
mesh_terms: D000217:Acyltransferases / Q000378:metabolism*; D002384:Catalysis; D003042:Cocaine / Q000031:analogs & derivatives / Q000032:analysis / Q000096:biosynthesis*; D030921:Erythroxylaceae / Q000201:enzymology / Q000378:metabolism; D058503:Mesophyll Cells / Q000201:enzymology / Q000378:metabolism; D018515:Plant Leaves / Q000201:enzymology / Q000378:metabolism; D010940:Plant Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D010940:Plant Proteins; D000217:Acyltransferases; D003042:Cocaine; C034029:cinnamoylcocaine