title: A ribozyme for the aldol reaction.
abstract: Directed in vitro evolution can create RNA catalysts for a variety of organic reactions, supporting the "RNA world" hypothesis, which proposes that metabolic transformations in early life were catalyzed by RNA molecules rather than proteins. Among the most fundamental carbon-carbon bond-forming reactions in nature is the aldol reaction, mainly catalyzed by aldolases that utilize either an enamine mechanism (class I) or a Zn(2+) cofactor (class II). We report on isolation of a Zn(2+)-dependent ribozyme that catalyzes an aldol reaction at its own modified 5' end with a 4300-fold rate enhancement over the uncatalyzed background reaction. The ribozyme can also act as an intermolecular catalyst that transfers a biotinylated benzaldehyde derivative to the aldol donor substrate, coupled to an external hexameric RNA oligonucleotide, supporting the existence of RNA-originated biosynthetic pathways for metabolic sugar precursors and other biomolecules.
authors.affiliation: Universität Bonn, Kekulé-Institut für Organische Chemie und Biochemie, Gerhard-Domagk-Strasse 1, 53121 Bonn, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Fusz
authors.forename: Alexander
authors.initials: A
authors.lastname: Eisenführ
authors.forename: Seergazhi G
authors.initials: SG
authors.lastname: Srivatsan
authors.forename: Alexander
authors.initials: A
authors.lastname: Heckel
authors.forename: Michael
authors.initials: M
authors.lastname: Famulok
mesh_terms: D000447:Aldehydes / Q000737:chemistry*; D001547:Benzaldehydes / Q000737:chemistry; D002384:Catalysis; D019020:Directed Molecular Evolution; D009690:Nucleic Acid Conformation; D009843:Oligoribonucleotides / Q000737:chemistry; D016337:RNA, Catalytic / Q000737:chemistry* / Q000302:isolation & purification; D015032:Zinc
chemical_list: D000447:Aldehydes; D001547:Benzaldehydes; D009843:Oligoribonucleotides; D016337:RNA, Catalytic; C116609:3-hydroxybutanal; D015032:Zinc