title: Inter- and intramolecular aldol reactions promiscuously catalyzed by a proline-based tautomerase.
abstract: The enzyme 4-oxalocrotonate tautomerase (4-OT), which in nature catalyzes a tautomerization step as part of a catabolic pathway for aromatic hydrocarbons, was found to promiscuously catalyze different types of aldol reactions. These include the self-condensation of propanal, the cross-coupling of propanal and benzaldehyde, the cross-coupling of propanal and pyruvate, and the intramolecular cyclizations of hexanedial and heptanedial. Mutation of the catalytic amino-terminal proline (P1A) greatly reduces 4-OT's aldolase activities, whereas mutation of another active site residue (F50A) strongly enhances 4-OT's aldolase activities, indicating that aldolization is an active site process. This catalytic promiscuity of 4-OT could be exploited as starting point to create tailor-made, artificial aldolases for challenging self- and cross-aldolizations.
authors.affiliation: Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands. g.j.poelarends@rug.nl.
authors.forename: Mehran
authors.initials: M
authors.lastname: Rahimi
authors.affiliation: Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands. g.j.poelarends@rug.nl.
authors.forename: Edzard M
authors.initials: EM
authors.lastname: Geertsema
authors.affiliation: Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands. g.j.poelarends@rug.nl.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Miao
authors.affiliation: Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands. g.j.poelarends@rug.nl.
authors.forename: Jan-Ytzen
authors.initials: JY
authors.lastname: van der Meer
authors.affiliation: Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands. g.j.poelarends@rug.nl.
authors.forename: Thea
authors.initials: T
authors.lastname: van den Bosch
authors.affiliation: Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands. g.j.poelarends@rug.nl.
authors.forename: Pim
authors.initials: P
authors.lastname: de Haan
authors.affiliation: Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands. g.j.poelarends@rug.nl.
authors.forename: Ellen
authors.initials: E
authors.lastname: Zandvoort
authors.affiliation: Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands. g.j.poelarends@rug.nl.
authors.forename: Gerrit J
authors.identifier: http://orcid.org/0000-0002-6917-6368
authors.initials: GJ
authors.lastname: Poelarends
mesh_terms: D000447:Aldehydes / Q000737:chemistry / Q000378:metabolism*; D055162:Biocatalysis; D007535:Isomerases / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure; D011392:Proline / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000447:Aldehydes; D011392:Proline; C021918:4-oxalocrotonate tautomerase; D007535:Isomerases