title: Genome-guided investigation of plant natural product biosynthesis.
abstract: The medicinal plant Madagascar periwinkle, Catharanthus roseus (L.) G. Don, produces hundreds of biologically active monoterpene-derived indole alkaloid (MIA) metabolites and is the sole source of the potent, expensive anti-cancer compounds vinblastine and vincristine. Access to a genome sequence would enable insights into the biochemistry, control, and evolution of genes responsible for MIA biosynthesis. However, generation of a near-complete, scaffolded genome is prohibitive to small research communities due to the expense, time, and expertise required. In this study, we generated a genome assembly for C. roseus that provides a near-comprehensive representation of the genic space that revealed the genomic context of key points within the MIA biosynthetic pathway including physically clustered genes, tandem gene duplication, expression sub-functionalization, and putative neo-functionalization. The genome sequence also facilitated high resolution co-expression analyses that revealed three distinct clusters of co-expression within the components of the MIA pathway. Coordinated biosynthesis of precursors and intermediates throughout the pathway appear to be a feature of vinblastine/vincristine biosynthesis. The C. roseus genome also revealed localization of enzyme-rich genic regions and transporters near known biosynthetic enzymes, highlighting how even a draft genome sequence can empower the study of high-value specialized metabolites.
authors.affiliation: Department of Biological Chemistry, The John Innes Centre, Norwich, NR4 7UH, UK.
authors.forename: Franziska
authors.initials: F
authors.lastname: Kellner
authors.affiliation: Department of Plant Biology, Michigan State University, East Lansing, MI, 48824, USA.
authors.forename: Jeongwoon
authors.initials: J
authors.lastname: Kim
authors.affiliation: The Genome Analysis Centre, Norwich, NR4 7UH, UK.
authors.forename: Bernardo J
authors.initials: BJ
authors.lastname: Clavijo
authors.affiliation: Department of Plant Biology, Michigan State University, East Lansing, MI, 48824, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Hamilton
authors.affiliation: Department of Plant Biology, Michigan State University, East Lansing, MI, 48824, USA.
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Childs
authors.affiliation: Department of Plant Biology, Michigan State University, East Lansing, MI, 48824, USA.
authors.forename: Brieanne
authors.initials: B
authors.lastname: Vaillancourt
authors.affiliation: Department of Plant Biology, Michigan State University, East Lansing, MI, 48824, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Cepela
authors.affiliation: Department of Plant Biology, Michigan State University, East Lansing, MI, 48824, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Habermann
authors.affiliation: The Sainsbury Laboratory, Norwich, NR4 7UH, UK.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Steuernagel
authors.affiliation: The Genome Analysis Centre, Norwich, NR4 7UH, UK.
authors.forename: Leah
authors.initials: L
authors.lastname: Clissold
authors.affiliation: The Genome Analysis Centre, Norwich, NR4 7UH, UK.
authors.forename: Kirsten
authors.initials: K
authors.lastname: McLay
authors.affiliation: Department of Plant Biology, Michigan State University, East Lansing, MI, 48824, USA.
authors.forename: Carol Robin
authors.initials: CR
authors.lastname: Buell
authors.affiliation: Department of Biological Chemistry, The John Innes Centre, Norwich, NR4 7UH, UK.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: O'Connor
mesh_terms: D001688:Biological Products / Q000378:metabolism*; D030008:Catharanthus / Q000378:metabolism*; D018506:Gene Expression Regulation, Plant; D018745:Genome, Plant / Q000235:genetics; D014747:Vinblastine / Q000378:metabolism
chemical_list: D001688:Biological Products; D014747:Vinblastine
keywords: Catharanthus roseus; alkaloid; genome; specialized metabolite; vinblastine