title: Genome-Wide Prediction of Metabolic Enzymes, Pathways, and Gene Clusters in Plants.
abstract: Plant metabolism underpins many traits of ecological and agronomic importance. Plants produce numerous compounds to cope with their environments but the biosynthetic pathways for most of these compounds have not yet been elucidated. To engineer and improve metabolic traits, we need comprehensive and accurate knowledge of the organization and regulation of plant metabolism at the genome scale. Here, we present a computational pipeline to identify metabolic enzymes, pathways, and gene clusters from a sequenced genome. Using this pipeline, we generated metabolic pathway databases for 22 species and identified metabolic gene clusters from 18 species. This unified resource can be used to conduct a wide array of comparative studies of plant metabolism. Using the resource, we discovered a widespread occurrence of metabolic gene clusters in plants: 11,969 clusters from 18 species. The prevalence of metabolic gene clusters offers an intriguing possibility of an untapped source for uncovering new metabolite biosynthesis pathways. For example, more than 1,700 clusters contain enzymes that could generate a specialized metabolite scaffold (signature enzymes) and enzymes that modify the scaffold (tailoring enzymes). In four species with sufficient gene expression data, we identified 43 highly coexpressed clusters that contain signature and tailoring enzymes, of which eight were characterized previously to be functional pathways. Finally, we identified patterns of genome organization that implicate local gene duplication and, to a lesser extent, single gene transposition as having played roles in the evolution of plant metabolic gene clusters.
authors.affiliation: Carnegie Institution for Science, Plant Biology Department, Stanford, California 94305 (P.S., P.Z., C.W., T.K., M.B., L.C., K.D., A.K.C., R.N.-P., S.Y.R.); and.|Laboratoire Biométrie et Biologie Evolutive, Université de Lyon, Université Lyon 1, Centre National de la Recherche Scientifique, Institut National de la Recherche Agronomique, Unité Mixte de Recherche 5558, 69622 Villeurbanne, France (T.B., D.K.).
authors.forename: Pascal
authors.identifier: 0000-0002-0828-8681
authors.initials: P
authors.lastname: Schläpfer
authors.affiliation: Carnegie Institution for Science, Plant Biology Department, Stanford, California 94305 (P.S., P.Z., C.W., T.K., M.B., L.C., K.D., A.K.C., R.N.-P., S.Y.R.); and.|Laboratoire Biométrie et Biologie Evolutive, Université de Lyon, Université Lyon 1, Centre National de la Recherche Scientifique, Institut National de la Recherche Agronomique, Unité Mixte de Recherche 5558, 69622 Villeurbanne, France (T.B., D.K.).
authors.forename: Peifen
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Carnegie Institution for Science, Plant Biology Department, Stanford, California 94305 (P.S., P.Z., C.W., T.K., M.B., L.C., K.D., A.K.C., R.N.-P., S.Y.R.); and.|Laboratoire Biométrie et Biologie Evolutive, Université de Lyon, Université Lyon 1, Centre National de la Recherche Scientifique, Institut National de la Recherche Agronomique, Unité Mixte de Recherche 5558, 69622 Villeurbanne, France (T.B., D.K.).
authors.forename: Chuan
authors.identifier: 0000-0001-5143-1714
authors.initials: C
authors.lastname: Wang
authors.affiliation: Carnegie Institution for Science, Plant Biology Department, Stanford, California 94305 (P.S., P.Z., C.W., T.K., M.B., L.C., K.D., A.K.C., R.N.-P., S.Y.R.); and.|Laboratoire Biométrie et Biologie Evolutive, Université de Lyon, Université Lyon 1, Centre National de la Recherche Scientifique, Institut National de la Recherche Agronomique, Unité Mixte de Recherche 5558, 69622 Villeurbanne, France (T.B., D.K.).
authors.forename: Taehyong
authors.initials: T
authors.lastname: Kim
authors.affiliation: Carnegie Institution for Science, Plant Biology Department, Stanford, California 94305 (P.S., P.Z., C.W., T.K., M.B., L.C., K.D., A.K.C., R.N.-P., S.Y.R.); and.|Laboratoire Biométrie et Biologie Evolutive, Université de Lyon, Université Lyon 1, Centre National de la Recherche Scientifique, Institut National de la Recherche Agronomique, Unité Mixte de Recherche 5558, 69622 Villeurbanne, France (T.B., D.K.).
authors.forename: Michael
authors.initials: M
authors.lastname: Banf
authors.affiliation: Carnegie Institution for Science, Plant Biology Department, Stanford, California 94305 (P.S., P.Z., C.W., T.K., M.B., L.C., K.D., A.K.C., R.N.-P., S.Y.R.); and.|Laboratoire Biométrie et Biologie Evolutive, Université de Lyon, Université Lyon 1, Centre National de la Recherche Scientifique, Institut National de la Recherche Agronomique, Unité Mixte de Recherche 5558, 69622 Villeurbanne, France (T.B., D.K.).
authors.forename: Lee
authors.identifier: 0000-0001-8183-2674
authors.initials: L
authors.lastname: Chae
authors.affiliation: Carnegie Institution for Science, Plant Biology Department, Stanford, California 94305 (P.S., P.Z., C.W., T.K., M.B., L.C., K.D., A.K.C., R.N.-P., S.Y.R.); and.|Laboratoire Biométrie et Biologie Evolutive, Université de Lyon, Université Lyon 1, Centre National de la Recherche Scientifique, Institut National de la Recherche Agronomique, Unité Mixte de Recherche 5558, 69622 Villeurbanne, France (T.B., D.K.).
authors.forename: Kate
authors.identifier: 0000-0003-4652-4398
authors.initials: K
authors.lastname: Dreher
authors.affiliation: Carnegie Institution for Science, Plant Biology Department, Stanford, California 94305 (P.S., P.Z., C.W., T.K., M.B., L.C., K.D., A.K.C., R.N.-P., S.Y.R.); and.|Laboratoire Biométrie et Biologie Evolutive, Université de Lyon, Université Lyon 1, Centre National de la Recherche Scientifique, Institut National de la Recherche Agronomique, Unité Mixte de Recherche 5558, 69622 Villeurbanne, France (T.B., D.K.).
authors.forename: Arvind K
authors.initials: AK
authors.lastname: Chavali
authors.affiliation: Carnegie Institution for Science, Plant Biology Department, Stanford, California 94305 (P.S., P.Z., C.W., T.K., M.B., L.C., K.D., A.K.C., R.N.-P., S.Y.R.); and.|Laboratoire Biométrie et Biologie Evolutive, Université de Lyon, Université Lyon 1, Centre National de la Recherche Scientifique, Institut National de la Recherche Agronomique, Unité Mixte de Recherche 5558, 69622 Villeurbanne, France (T.B., D.K.).
authors.forename: Ricardo
authors.initials: R
authors.lastname: Nilo-Poyanco
authors.affiliation: Carnegie Institution for Science, Plant Biology Department, Stanford, California 94305 (P.S., P.Z., C.W., T.K., M.B., L.C., K.D., A.K.C., R.N.-P., S.Y.R.); and.|Laboratoire Biométrie et Biologie Evolutive, Université de Lyon, Université Lyon 1, Centre National de la Recherche Scientifique, Institut National de la Recherche Agronomique, Unité Mixte de Recherche 5558, 69622 Villeurbanne, France (T.B., D.K.).
authors.forename: Thomas
authors.initials: T
authors.lastname: Bernard
authors.affiliation: Carnegie Institution for Science, Plant Biology Department, Stanford, California 94305 (P.S., P.Z., C.W., T.K., M.B., L.C., K.D., A.K.C., R.N.-P., S.Y.R.); and.|Laboratoire Biométrie et Biologie Evolutive, Université de Lyon, Université Lyon 1, Centre National de la Recherche Scientifique, Institut National de la Recherche Agronomique, Unité Mixte de Recherche 5558, 69622 Villeurbanne, France (T.B., D.K.).
authors.forename: Daniel
authors.identifier: 0000-0001-8093-0854
authors.initials: D
authors.lastname: Kahn
authors.affiliation: Carnegie Institution for Science, Plant Biology Department, Stanford, California 94305 (P.S., P.Z., C.W., T.K., M.B., L.C., K.D., A.K.C., R.N.-P., S.Y.R.); and srhee@carnegiescience.edu.|Laboratoire Biométrie et Biologie Evolutive, Université de Lyon, Université Lyon 1, Centre National de la Recherche Scientifique, Institut National de la Recherche Agronomique, Unité Mixte de Recherche 5558, 69622 Villeurbanne, France (T.B., D.K.) srhee@carnegiescience.edu.
authors.forename: Seung Y
authors.identifier: 0000-0002-7572-4762
authors.initials: SY
authors.lastname: Rhee
mesh_terms: D053898:Biosynthetic Pathways / Q000235:genetics; D019295:Computational Biology / Q000379:methods; D019143:Evolution, Molecular; D020440:Gene Duplication; D018506:Gene Expression Regulation, Plant; D018745:Genome, Plant / Q000235:genetics*; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D008957:Models, Genetic; D005810:Multigene Family / Q000235:genetics*; D010940:Plant Proteins / Q000235:genetics / Q000378:metabolism; D010944:Plants / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D013045:Species Specificity
chemical_list: D010940:Plant Proteins