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Biochemical characterization of the minimal domains of an iterative eukaryotic polyketide synthase

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dc.citation.titleFEBS Journales
dc.citation.volume285(23)es
dc.creatorSabatini, Martín
dc.creatorComba, Santiago
dc.creatorAltabe, Silvia Graciela
dc.creatorRecio Balsells, Alejandro Iván
dc.creatorLabadie, Guillermo Roberto
dc.creatorTakano, Eriko
dc.creatorGramajo, Hugo Cesar
dc.creatorArabolaza, Ana Lorena
dc.date.accessioned2020-05-27T22:03:03Z
dc.date.available2020-05-27T22:03:03Z
dc.date.issued2018-10-25
dc.descriptionIterative type I polyketide synthases (PKS) are megaenzymes essential to the biosynthesis of an enormously diverse array of bioactive natural products. Each PKS contains minimally three functional domains, β‐ketosynthase (KS), acyltransferase (AT), and acyl carrier protein (ACP), and a subset of reducing domains such as ketoreductase (KR), dehydratase (DH), and enoylreductase (ER). The substrate selection, condensation reactions, and β‐keto processing of the polyketide growing chain are highly controlled in a programmed manner. However, the structural features and mechanistic rules that orchestrate the iterative cycles, processing domains functionality, and chain termination in this kind of megaenzymes are often poorly understood. Here, we present a biochemical and functional characterization of the KS and the AT domains of a PKS from the mallard duck Anas platyrhynchos (ApPKS). ApPKS belongs to an animal PKS family phylogenetically more related to bacterial PKS than to metazoan fatty acid synthases. Through the dissection of the ApPKS enzyme into mono‐ to didomain fragments and its reconstitution in vitro, we determined its substrate specificity toward different starters and extender units. ApPKS AT domain can effectively transfer acetyl‐CoA and malonyl‐CoA to the ApPKS ACP stand‐alone domain. Furthermore, the KS and KR domains, in the presence of Escherichia coli ACP, acetyl‐CoA, and malonyl‐CoA, showed the ability to catalyze the chain elongation and the β‐keto reduction steps necessary to yield a 3‐hydroxybutyryl‐ACP derivate. These results provide new insights into the catalytic efficiency and specificity of this uncharacterized family of PKSs.es
dc.description.filFil: Sabatini, Martín. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.es
dc.description.filFil: Comba, Santiago. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.es
dc.description.filFil: Altabe, Silvia Graciela. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.es
dc.description.filFil: Recio Balsells, Alejandro Iván. Universidad Nacional del Rosario. Facultad de Ciencias Bioquímicas y Farmaceúticas. Instituto de Química Rosario (IQUIR-CONICET); Argentina.es
dc.description.filFil: Labadie, Guillermo Roberto. Universidad Nacional del Rosario. Facultad de Ciencias Bioquímicas y Farmaceúticas. Instituto de Química Rosario (IQUIR-CONICET); Argentina.es
dc.description.filFil: Takano, Eriko. University of Manchester. Manchester Institute of Biotechnology (MIB). Manchester Centre of Fine and Specialty Chemicals (SYNBIOCHEM); United Kingdom.es
dc.description.filFil: Gramajo, Hugo Cesar. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.es
dc.description.filFil: Arabolaza, Ana Lorena. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.es
dc.description.sponsorshipUniversity of Manchester Research Initiative on ‘Targeting GCRF Applications in Industrial Biotechnology: Enhancing International Collaborations’es
dc.description.sponsorshipBiotechnology and Biological Sciences Research Council (BBSRC)es
dc.description.sponsorshipEngineering and Physical Sciences Research Council (EPSRC). Grant Number: BB/M017702/1es
dc.formatapplication/pdf
dc.format.extent4494-4511es
dc.identifier.issn1742-464Xes
dc.identifier.urihttp://hdl.handle.net/2133/18276
dc.language.isoenges
dc.publisherWileyes
dc.relation.publisherversionhttps://doi.org/10.1111/febs.14675es
dc.relation.publisherversionhttps://febs.onlinelibrary.wiley.com/doi/full/10.1111/febs.14675es
dc.rightsopenAccesses
dc.rights.holderSabatini, Martínes
dc.rights.holderComba, Santiagoes
dc.rights.holderAltabe, Silvia Gracielaes
dc.rights.holderRecio Balsells, Alejandro Ivánes
dc.rights.holderLabadie, Guillermo Robertoes
dc.rights.holderTakano, Erikoes
dc.rights.holderGramajo, Hugo Cesares
dc.rights.holderArabolaza, Ana Lorenaes
dc.rights.holderUniversidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticases
dc.rights.textAtribución 4.0 Internacional (CC BY 4.0)es
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/deed.es*
dc.subjectDomain deconstructiones
dc.subjectIterative PKSes
dc.subjectPKS biochemistryes
dc.subjectSubstrate specificityes
dc.titleBiochemical characterization of the minimal domains of an iterative eukaryotic polyketide synthasees
dc.typearticle
dc.typeartículo
dc.typepublishedVersion
dc.type.collectionarticulo
dc.type.versionpublishedVersiones

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