Carboligation towards production of hydroxypentanones

2-Hydroxy-3-pentanone and 3-hydroxy-2-pentanone are flavor molecules present in various foods, such as cheese, wine, durian, and honey, where they impart buttery, hay-like, and caramel-sweet aromas. However, their utilization as flavoring agents is constrained by a lack of developed synthesis methods. In this study, we present their synthesis from simple starting compounds available in natural quality, catalyzed by previously characterized ThDP-dependent carboligases. Additionally, we demonstrate that newly discovered homologues of pyruvate dehydrogenase from E. coli (EcPDH E1), namely LaPDH from Leclercia adecarboxylata, CnPDH from Cupriavidus necator, and TcPDH from Tanacetum cinerariifolium, exhibit promising potential for α-hydroxy pentanone synthesis in form of whole-cell biocatalysts. Enzyme stability at varying pH levels, kinetic parameters, and reaction intensification were investigated. CnPDH, for example, exhibits superior stability across different pH levels compared to EcPDH E1. Both α-hydroxy pentanones can be produced with CnPDH in satisfactory yields (74% and 59%, respectively).