Polyphosphate Kinase from Burkholderia cenocepacia, One Enzyme Catalyzing a Two-Step Cascade Reaction to Synthesize ATP from AMP

This study characterizes a novel polyphosphate kinase from Burkholderia cenocepacia (BcPPK2-III), an enzyme with potential applications in ATP regeneration processes. Bioinformatic and structural analyses confirmed the presence of conserved motifs characteristic of PPK2 enzymes, including Walker A a...

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Detalles Bibliográficos
Autores: Monterrey, Dianélis T., Azcona, Leire, Revuelta, Julia, Sánchez-Moreno, Israel, García-Junceda, Eduardo
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/373652
Acceso en línea:http://hdl.handle.net/10261/373652
Access Level:acceso abierto
Palabra clave:Biocatalysis
ATP regeneration
Polyphosphate
Polyphosphate kinase
Cofactor recycling
Cascade reactions
Descripción
Sumario:This study characterizes a novel polyphosphate kinase from Burkholderia cenocepacia (BcPPK2-III), an enzyme with potential applications in ATP regeneration processes. Bioinformatic and structural analyses confirmed the presence of conserved motifs characteristic of PPK2 enzymes, including Walker A and B motifs, and the subclass-specific residue E137. Molecular docking simulations showed AMP had the highest binding affinity (−7.0 kcal/mol), followed by ADP (−6.5 kcal/mol), with ATP having the lowest affinity (−6.3 kcal/mol). It was overexpressed in Escherichia coli, after purification enzymatic activity assays revealed that BcPPK2-III needed divalent cations (Mg2⁺, Mn2⁺, Co2⁺) as cofactors to be active. Functional assays revealed its ability to synthesize ATP from AMP through a stepwise phosphorylation mechanism, forming ADP as an intermediate, achieving 70% ATP conversion (TTN 4354.7) after 24 h. Kinetic studies indicated cooperative behavior and substrate preference, with AMP phosphorylation to ADP being the most efficient step. The enzyme demonstrated high thermostability (T50 = 62 °C) and a broad pH stability range (pH 6.0–9.0), making it suitable for diverse biocatalytic applications. The study highlights BcPPK2-III as a robust and versatile candidate for cost-effective ATP regeneration, offering advantages in industrial processes requiring stoichiometric amounts of ATP.